Objective: The study aims to evaluate the protective effects of coenzyme Q10 (CoQ10) and Cynara scolymus L (CS) on doxorubicin (dox)-induced toxicity.
Materials and Methods: Sixty male rats were divided into six groups. Group 1 as a control. Group 2 received dox (10 mg/kg) intraperitoneally. Group 3 received CoQ10 (200 mg/kg). Group 4 received CS (500 mg/kg). Group 5 received CoQ10 (200 mg/kg) and dox (10 mg/kg). Group 6 received CS (500 mg/kg) and dox (10 mg/kg). The rats were then evaluated biochemically and immunohistochemically.
Results: Dox produced a significant deterioration of hepatic and renal functional parameters. Moreover, an upsurge of oxidative stress and nitrosative stress markers. The expression of alpha-smooth muscle actin (α-SMA) was increased and proliferating cell nuclear antigen (PCNA) expression was decreased. Administration of CoQ10 and CS resulted in a significant improvement of hepatic and renal functional parameters, and an improvement of both α-SMA and PCNA.
Conclusion: It is concluded that pretreatment with CoQ10 and CS is associated with up-regulation of favorable protective enzymes and down-regulation of oxidative stress. That can be advised as a supplement to dox-treated patients.
Keywords: Alpha-smooth muscle actin, doxorubicin, nitrosative, oxidative, proliferating cell nuclear antigen
International Journal of Engineering and Science Invention (IJESI)inventionjournals
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Does allicin combined with vitamin B-complex have superior potentials than al...Prof. Hesham N. Mustafa
BACKGROUND:
The current article aims to explore the protective potentials of α-tocopherol alone and the combination of allicin and vitamin B-complex against lead-acetate neurotoxicity on the cerebellar cortex.
MATERIALS AND METHODS:
Forty rats were divided into four groups (n=10). Group 1 was the control group. Group 2 received 10 mg/kg body weight (BW) of lead acetate. Group 3 was exposed to 10 mg/kg BW of lead acetate plus a combination of allicin (100 mg/kg BW) and vit. B-complex (40 mg/kg BW). Group 4 was administered lead acetate (10 mg/kg BW) and α-tocopherol (100 mg/kg BW). The animals received treatment for sixty days by oral gavage. All the groups were studied ultrastructurally and immunohistochemically with glial fibrillary acidic protein (GFAP).
RESULTS:
The affected groups revealed shrunken and degenerated Purkinje cells with irregular nuclei. The cytoplasm comprised several lysosomes, unhealthy mitochondria, and dilated Golgi saccules. The myelinated nerve fibers demonstrated breaking of the myelin sheaths, apparent vacuoles, and broad axonal spaces. Immunohistochemically, there was a tremendous surge in GFAP-positive astrocytes in the lead acetate-treated group. These histological and ultrastructural variations were ameliorated by the administration of α-tocopherol and the combination of allicin and vit. B complex. Moreover, an apparent decrease in the number of GFAP-positive astrocytes was obvious in the protected groups.
CONCLUSIONS:
Although both α-tocopherol and the combination of allicin and vit. B-complex can be used as possible adjuvant therapies to ameliorate nervous system ailments attributable to lead acetate, α-tocopherol showed more protective potential.
KEYWORDS:
Allicin; Astrocytes; GFAP; Myelin Figure; Oligodendrocyte; Purkinje cells
International Journal of Engineering and Science Invention (IJESI)inventionjournals
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Does allicin combined with vitamin B-complex have superior potentials than al...Prof. Hesham N. Mustafa
BACKGROUND:
The current article aims to explore the protective potentials of α-tocopherol alone and the combination of allicin and vitamin B-complex against lead-acetate neurotoxicity on the cerebellar cortex.
MATERIALS AND METHODS:
Forty rats were divided into four groups (n=10). Group 1 was the control group. Group 2 received 10 mg/kg body weight (BW) of lead acetate. Group 3 was exposed to 10 mg/kg BW of lead acetate plus a combination of allicin (100 mg/kg BW) and vit. B-complex (40 mg/kg BW). Group 4 was administered lead acetate (10 mg/kg BW) and α-tocopherol (100 mg/kg BW). The animals received treatment for sixty days by oral gavage. All the groups were studied ultrastructurally and immunohistochemically with glial fibrillary acidic protein (GFAP).
RESULTS:
The affected groups revealed shrunken and degenerated Purkinje cells with irregular nuclei. The cytoplasm comprised several lysosomes, unhealthy mitochondria, and dilated Golgi saccules. The myelinated nerve fibers demonstrated breaking of the myelin sheaths, apparent vacuoles, and broad axonal spaces. Immunohistochemically, there was a tremendous surge in GFAP-positive astrocytes in the lead acetate-treated group. These histological and ultrastructural variations were ameliorated by the administration of α-tocopherol and the combination of allicin and vit. B complex. Moreover, an apparent decrease in the number of GFAP-positive astrocytes was obvious in the protected groups.
CONCLUSIONS:
Although both α-tocopherol and the combination of allicin and vit. B-complex can be used as possible adjuvant therapies to ameliorate nervous system ailments attributable to lead acetate, α-tocopherol showed more protective potential.
KEYWORDS:
Allicin; Astrocytes; GFAP; Myelin Figure; Oligodendrocyte; Purkinje cells
Hyperoxaluria Induces Oxidative DNA Damage and Results in Renal Tubular Epithelial Cell Apoptosis: A Clue to the Pathogenesis of Urolithiasis by Hasan Aydin in Experimental Techniques in Urology & Nephrology
Ameliorative potentials of a combination of fenugreek and alpha-tocopherol on...Prof. Hesham N. Mustafa
Background: The current study aimed to elucidate the protective role of combined fenugreek and a-tocopherol against cadmium induced histopathological
changes in the testes.
Materials and methods: Thirty adult male albino rats divided into three equal
groups 10 rats each. Group I is the control group. Group II received 5 mg/kg/day
cadmium chloride. Group III received 5 mg/kg/day cadmium chloride and 150
mg/kg/day fenugreek and 100 mg/kg/day of a-tocopherol. The treatment of all
groups was done by oral gavage for 60 consecutive days. The testes were removed
and subjected to histopathological and ultrastructure study.
Results: Rats exposed to cadmium showed severe histopathological changes in
the testicular spermatogenic series, many vacuoles and multinucleated giant cells.
Treatment with fenugreek and a-tocopherol partially improved the morphological
changes, reduced tissue damage and rebuilt of the spermatogonia layer.
Conclusions: Fenugreek and a-tocopherol might represent a promising medicinal
combination to ameliorate the toxic effects of cadmium exposure. (Folia Morphol
2015; 74, 3: 325–334)
Key words: cadmium chloride, fenugreek, a-tocopherol, seminiferous
epithelium, ultrastructure
Histopathological effects of nanosilver (Ag-NPs) in liver after dermal exposu...Nanomedicine Journal (NMJ)
Objective(s):
With the advent of nanotechnology, significant progress has been made in the area of nanoscale materials such as nanosilver (Ag-Nps). These nanoparticles have a wide range of applications and been used for antimicrobial purposes for more than a century. However, little
attention has been paid to the toxicity of nanosilver wound dressing. This study was designed to investigate the possible histopathological toxicity of Ag-NPs in liver of mice during wound healing.
Materials and Methods:
A group of 50 female BALB/c mice of about 8 weeks were randomly divided into two groups: Ag-NPs and control groups (n=25). After creating similar wound on the backs of all animals, the wound bed was treated in Ag-NPs group, with a volume of 50 microliters of the nanosilver solution (10ppm) ,and in control group, with the same amount of distilled water. The experiment lasted for 14 days. Histopathaological samplings of liver were conducted on days 2, 7 and 14 of the experiment.
Results:
Histopathological studies demonstrated time-dependent changes in mice liver treated with Ag-NPs compared to control group. Some changes include dilation in central venous, hyperemia, cell swelling, increase of Kupffer and inflammatory cells.
Conclusion:
This study suggests that use of nanosilver for wound healing may cause a mild toxicity, as indicated by time-dependent toxic responses in liver tissue. However, this issue will have to be considered more extensively in further studies
Brazilian Red Propolis Attenuates Hypertension and Renal DamageBee Healthy Farms
Incorporating Brazilian Red Propolis in the diet of rats with reduced kidney function experienced a reduction of hypertension and renal damage. This scenario simulated Chronic Kidney Disease.and found the anti-inflammatory and antioxidant effects of Brazilian Red Propolis effective but requires additional studies to determine which mechanisms were prominent.
Abstract
Objective(s):
Gold nanoparticles (GNPs) command a great deal of attention for biomedical applications nowadays. The data about the degree of toxicity and the accumulation of gold nanoparticles in-vivo is not enough to judge.
Materials and Methods:
A total of 32 healthy male Wistar rats were randomly divided into 4 including: three GNP-treated and one control group. Groups 1, 2 and 3 received 0.5 cc of a solution containing 5, 10, and 100 ppm Au daily via intraperitoneal (IP) injection for 7 days, respectively. The control group was treated with 0.5 cc normal saline with same procedure. Then, several biochemical parameters such as serum glutamate oxaloacetat transaminase (SGOT) and serum glutamate pyrvate transaminase (SGPT) were evaluated at 2, 7 and 14 days after the last injection. After 14 days, all the rats were sacrificed and liver, lung tissues were separated and evaluated.
Results:
SGOT two days after intervention was significantly greater in the group 2 than the control group. In liver histological assessment, in group 1, basophils were observed around the central veins, in group 2 fading and no observation of central veins was seen, and in group 3 hepatic damage was noticed. The lung histological results showed severe vascular hyperemia in group 1, air sacs damage in group 2, and complete air sacs destruction in group 3.
Conclusion:
The results showed extreme changes in the histopathology of lung and liver tissues caused by spherical nanogold with 5-10 nm size in all of three treatment groups.
The relationship between progesterone and biochemical constituents of amnioti...Ali Olfati
Ali Olfati1, Gholamali Moghaddam1, Nasroallah Moradi Kor2*, Mitra Bakhtiari3
1Department of Animal Science, Faculty of Agriculture, University of Tabriz, Iran
2Department of Reproduction Physiologies, Iranian Society of Physiology and Pharmacology, Tehran, Iran
3Department of Anatomical Sciences, Faculty of Medicine, University of Medical Sciences, Kermanshah, Iran
Objective: To investigate the protective effect of lo- sartan, an angiotensin II type 1 receptor blocker with antioxidative effect on intestinal ischemia-reperfusion (I/R) injury in rats, against inflammation and apoptotic development.
Study Design: Forty male Wistar albino rats with a mean weight of 200–250 g each were divided into 4 groups: (1) Sham operation (laparotomy only, sham surgical preparation including isolation of the superior mesenteric artery [SMA] without occlusion), (2) Ischemia model with SMA closure for 2 hours, (3) I/R group (2 hours of ischemia followed by 3-hour reperfusion (SMA occlusion for 120 minutes followed by 240 minutes reperfusion), and (4) Losartan group (2 hours of ischemia, 40 mg/kg losartan was administered to the animals; losartan was dissolved in 1 mL distilled water and administered intraperitoneally after 2 hours of ischemia). Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were examined in jejunum tissue.
Results: Losartan treatment reduced the I/R-induced increase in MDA levels in the gut. Statistically, while SOD, CAT, and GSH activities decreased significantly in the I/R group, they increased in the I/R+Losartan group. Villus loss and increase in inflammation after ischemia persisted after reperfusion. Losartan treatment played a role in the reduction of inflammation and apoptosis and in the regulation of TNF-α and caspase-9 activity.
Conclusion: It has been thought that losartan in I/R may reduce mucosal damage and cell apoptosis in the direction of inflammation and may stabilize caspase-9 activity by inhibiting TNF-α stimulus.
Keywords: caspase-9, ischemia, ischemia/reperfusion, rat, reperfusion injury, TNF-α, tumor necrosis factor-alpha
Hepatoprotective Activity of Chara Parpam in Ccl4 Induced RatsIOSR Journals
Siddha system of medicine provides most frequently and to the extent possible and promising therapy for the relief of signs and symptoms of liver disorder over the generations. Their high therapeutic quality and lack of toxicity are exceptional. The present experimental work was to evaluate the hepatoprotective properties of Siddha herbo-mineral formulation Chara Parpam by CCl4 induced hepatotoxicity in albino rats. Two doses of Chara Parpam (5 mg/kg and 10 mg/kg) were administered to rats. Protection of hepatocytes was evaluated by estimate the level of ALT, AST, ALP, serum bilirubin, total protein, serum albumin, sodium and potassium during the exposure of CCL4 on wistar albino rats and to evaluate the effect of different doses of Chara Parpam against hepatotoxicity induced by CCL4. Liver histology was performed 24 hours after the administration of trial drug Chara Parpam. The result indicated that the concentration of ALT, AST, and ALP, released by hepatocytes were significantly reduced in the presence of Chara Parpam. The cytoprotective effects of the Chara Parpam are dose-dependent. Through this work, we demonstrate for the first time the direct protection of liver cells by administration of Chara Parpam confirming its hepatoprotective properties.
Objective(s):
There is a rising use of gold nanoparticles (AuNPs) in goods and in the medical fields but there is concern about the toxicity of them. So in this study spherical AuNPs with 3 different concentrations were applied for investigating their effects in vivo.
Materials and Methods:
40 male albino mice were randomly divided into sham, control, 25 ppm, 50 ppm, 100 ppm groups and were treated by intraperitoneal injection for period of 14 days. Blood was taken for measuring of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase (SGOT and SGPT) enzyme levels and Complete Blood Count (CBC).
Results:
After the treatment and comparing groups with sham group, in 50 ppm group significant increases on RBC, HCT, HGB, MCHC and in 25 ppm group significant increase on MCHC and significant decrease on MCV and in 100 ppm group significant increase on MCHC were observed. Also in 50 ppm group an increase on SGOT enzyme level was observed. However, it was nonsignificant.
Conclusion:
By observing the abnormality on the RBC count and SGOT enzyme level in the 50 ppm group, we concluded a slight toxicity effect for AuNPs and the threat potential of their use in human.
Bee venom protects kidneys from cancer drug toxicityBee Healthy Farms
The findings strongly suggest that Bee Venom could prevent cisplatin-induced severe side effects in the kidney, at least partly, by modulating the Tregs. Bee Venom has protective effects on cisplatin-induced nephrotoxicity in mice, at least in part, through the regulation of Tregs without a big influence on the antitumor effects of cisplatin.
Hyperoxaluria Induces Oxidative DNA Damage and Results in Renal Tubular Epithelial Cell Apoptosis: A Clue to the Pathogenesis of Urolithiasis by Hasan Aydin in Experimental Techniques in Urology & Nephrology
Ameliorative potentials of a combination of fenugreek and alpha-tocopherol on...Prof. Hesham N. Mustafa
Background: The current study aimed to elucidate the protective role of combined fenugreek and a-tocopherol against cadmium induced histopathological
changes in the testes.
Materials and methods: Thirty adult male albino rats divided into three equal
groups 10 rats each. Group I is the control group. Group II received 5 mg/kg/day
cadmium chloride. Group III received 5 mg/kg/day cadmium chloride and 150
mg/kg/day fenugreek and 100 mg/kg/day of a-tocopherol. The treatment of all
groups was done by oral gavage for 60 consecutive days. The testes were removed
and subjected to histopathological and ultrastructure study.
Results: Rats exposed to cadmium showed severe histopathological changes in
the testicular spermatogenic series, many vacuoles and multinucleated giant cells.
Treatment with fenugreek and a-tocopherol partially improved the morphological
changes, reduced tissue damage and rebuilt of the spermatogonia layer.
Conclusions: Fenugreek and a-tocopherol might represent a promising medicinal
combination to ameliorate the toxic effects of cadmium exposure. (Folia Morphol
2015; 74, 3: 325–334)
Key words: cadmium chloride, fenugreek, a-tocopherol, seminiferous
epithelium, ultrastructure
Histopathological effects of nanosilver (Ag-NPs) in liver after dermal exposu...Nanomedicine Journal (NMJ)
Objective(s):
With the advent of nanotechnology, significant progress has been made in the area of nanoscale materials such as nanosilver (Ag-Nps). These nanoparticles have a wide range of applications and been used for antimicrobial purposes for more than a century. However, little
attention has been paid to the toxicity of nanosilver wound dressing. This study was designed to investigate the possible histopathological toxicity of Ag-NPs in liver of mice during wound healing.
Materials and Methods:
A group of 50 female BALB/c mice of about 8 weeks were randomly divided into two groups: Ag-NPs and control groups (n=25). After creating similar wound on the backs of all animals, the wound bed was treated in Ag-NPs group, with a volume of 50 microliters of the nanosilver solution (10ppm) ,and in control group, with the same amount of distilled water. The experiment lasted for 14 days. Histopathaological samplings of liver were conducted on days 2, 7 and 14 of the experiment.
Results:
Histopathological studies demonstrated time-dependent changes in mice liver treated with Ag-NPs compared to control group. Some changes include dilation in central venous, hyperemia, cell swelling, increase of Kupffer and inflammatory cells.
Conclusion:
This study suggests that use of nanosilver for wound healing may cause a mild toxicity, as indicated by time-dependent toxic responses in liver tissue. However, this issue will have to be considered more extensively in further studies
Brazilian Red Propolis Attenuates Hypertension and Renal DamageBee Healthy Farms
Incorporating Brazilian Red Propolis in the diet of rats with reduced kidney function experienced a reduction of hypertension and renal damage. This scenario simulated Chronic Kidney Disease.and found the anti-inflammatory and antioxidant effects of Brazilian Red Propolis effective but requires additional studies to determine which mechanisms were prominent.
Abstract
Objective(s):
Gold nanoparticles (GNPs) command a great deal of attention for biomedical applications nowadays. The data about the degree of toxicity and the accumulation of gold nanoparticles in-vivo is not enough to judge.
Materials and Methods:
A total of 32 healthy male Wistar rats were randomly divided into 4 including: three GNP-treated and one control group. Groups 1, 2 and 3 received 0.5 cc of a solution containing 5, 10, and 100 ppm Au daily via intraperitoneal (IP) injection for 7 days, respectively. The control group was treated with 0.5 cc normal saline with same procedure. Then, several biochemical parameters such as serum glutamate oxaloacetat transaminase (SGOT) and serum glutamate pyrvate transaminase (SGPT) were evaluated at 2, 7 and 14 days after the last injection. After 14 days, all the rats were sacrificed and liver, lung tissues were separated and evaluated.
Results:
SGOT two days after intervention was significantly greater in the group 2 than the control group. In liver histological assessment, in group 1, basophils were observed around the central veins, in group 2 fading and no observation of central veins was seen, and in group 3 hepatic damage was noticed. The lung histological results showed severe vascular hyperemia in group 1, air sacs damage in group 2, and complete air sacs destruction in group 3.
Conclusion:
The results showed extreme changes in the histopathology of lung and liver tissues caused by spherical nanogold with 5-10 nm size in all of three treatment groups.
The relationship between progesterone and biochemical constituents of amnioti...Ali Olfati
Ali Olfati1, Gholamali Moghaddam1, Nasroallah Moradi Kor2*, Mitra Bakhtiari3
1Department of Animal Science, Faculty of Agriculture, University of Tabriz, Iran
2Department of Reproduction Physiologies, Iranian Society of Physiology and Pharmacology, Tehran, Iran
3Department of Anatomical Sciences, Faculty of Medicine, University of Medical Sciences, Kermanshah, Iran
Objective: To investigate the protective effect of lo- sartan, an angiotensin II type 1 receptor blocker with antioxidative effect on intestinal ischemia-reperfusion (I/R) injury in rats, against inflammation and apoptotic development.
Study Design: Forty male Wistar albino rats with a mean weight of 200–250 g each were divided into 4 groups: (1) Sham operation (laparotomy only, sham surgical preparation including isolation of the superior mesenteric artery [SMA] without occlusion), (2) Ischemia model with SMA closure for 2 hours, (3) I/R group (2 hours of ischemia followed by 3-hour reperfusion (SMA occlusion for 120 minutes followed by 240 minutes reperfusion), and (4) Losartan group (2 hours of ischemia, 40 mg/kg losartan was administered to the animals; losartan was dissolved in 1 mL distilled water and administered intraperitoneally after 2 hours of ischemia). Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were examined in jejunum tissue.
Results: Losartan treatment reduced the I/R-induced increase in MDA levels in the gut. Statistically, while SOD, CAT, and GSH activities decreased significantly in the I/R group, they increased in the I/R+Losartan group. Villus loss and increase in inflammation after ischemia persisted after reperfusion. Losartan treatment played a role in the reduction of inflammation and apoptosis and in the regulation of TNF-α and caspase-9 activity.
Conclusion: It has been thought that losartan in I/R may reduce mucosal damage and cell apoptosis in the direction of inflammation and may stabilize caspase-9 activity by inhibiting TNF-α stimulus.
Keywords: caspase-9, ischemia, ischemia/reperfusion, rat, reperfusion injury, TNF-α, tumor necrosis factor-alpha
Hepatoprotective Activity of Chara Parpam in Ccl4 Induced RatsIOSR Journals
Siddha system of medicine provides most frequently and to the extent possible and promising therapy for the relief of signs and symptoms of liver disorder over the generations. Their high therapeutic quality and lack of toxicity are exceptional. The present experimental work was to evaluate the hepatoprotective properties of Siddha herbo-mineral formulation Chara Parpam by CCl4 induced hepatotoxicity in albino rats. Two doses of Chara Parpam (5 mg/kg and 10 mg/kg) were administered to rats. Protection of hepatocytes was evaluated by estimate the level of ALT, AST, ALP, serum bilirubin, total protein, serum albumin, sodium and potassium during the exposure of CCL4 on wistar albino rats and to evaluate the effect of different doses of Chara Parpam against hepatotoxicity induced by CCL4. Liver histology was performed 24 hours after the administration of trial drug Chara Parpam. The result indicated that the concentration of ALT, AST, and ALP, released by hepatocytes were significantly reduced in the presence of Chara Parpam. The cytoprotective effects of the Chara Parpam are dose-dependent. Through this work, we demonstrate for the first time the direct protection of liver cells by administration of Chara Parpam confirming its hepatoprotective properties.
Objective(s):
There is a rising use of gold nanoparticles (AuNPs) in goods and in the medical fields but there is concern about the toxicity of them. So in this study spherical AuNPs with 3 different concentrations were applied for investigating their effects in vivo.
Materials and Methods:
40 male albino mice were randomly divided into sham, control, 25 ppm, 50 ppm, 100 ppm groups and were treated by intraperitoneal injection for period of 14 days. Blood was taken for measuring of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase (SGOT and SGPT) enzyme levels and Complete Blood Count (CBC).
Results:
After the treatment and comparing groups with sham group, in 50 ppm group significant increases on RBC, HCT, HGB, MCHC and in 25 ppm group significant increase on MCHC and significant decrease on MCV and in 100 ppm group significant increase on MCHC were observed. Also in 50 ppm group an increase on SGOT enzyme level was observed. However, it was nonsignificant.
Conclusion:
By observing the abnormality on the RBC count and SGOT enzyme level in the 50 ppm group, we concluded a slight toxicity effect for AuNPs and the threat potential of their use in human.
Bee venom protects kidneys from cancer drug toxicityBee Healthy Farms
The findings strongly suggest that Bee Venom could prevent cisplatin-induced severe side effects in the kidney, at least partly, by modulating the Tregs. Bee Venom has protective effects on cisplatin-induced nephrotoxicity in mice, at least in part, through the regulation of Tregs without a big influence on the antitumor effects of cisplatin.
Evaluation of In-vitro neuroprotective effect of Ethanolic extract of Canariu...AI Publications
The ethanolic extract of canarium solomonense leaves (ecsl) was studied for its neuroprotective activity. The neuroprotective activity of ECSL was found to have a significant impact on neuronal cell death triggered by hydrogen peroxide (MTT assay) in human SH-SY5Y neuroblastoma cells. Scopolamine, a muscarinic receptor blocker, is frequently used to induce cognitive impairment in laboratory animals. Injections of scopolamine influence multiple cognitive functions, including motor function, short-term memory, and attention. Using the Morris water maze, the Y maze, and the passive avoidance paradigm, memory enhancing activity in scopolamine-induced amnesic rats was evaluated. Using the Morris water maze, the Y maze, and the passive avoidance paradigm, ECSL was found to have a substantial effect on the memory of scopolamine- induced amnesic rats. Our experimental data indicated that ECSL can reverse scopolamine induced amnesia and assist with memory issues.
ABSTRACT- The anticancer drug arsenic trioxide is effective for acute promyelocytic leukemia. But the clinical trials are
restricted due to its potential side effects. Since the major part of arsenic metabolism and detoxification occurs in liver,
this organ faces the major threat. The hepatic side effects include fatty liver, fibrosis, and inflammation and hepatocyte
degeneration. Our study aimed to evaluate the protective potential of the fatty acid, docosahexaenoic acid, against adversities
of arsenic trioxide in an in vitro model, the Chang liver cells. Two preliminary dose standardization assays, cell
viability and lactate dehydrogenase release assays, were employed. The assays were performed as Pre-treatment,
Co-treatment and Post treatment experiments for a period of 24 hours. Arsenic trioxide at various doses (2.5, 5, 7.5, 10,
12.5 and 15 μM) showed a significant (p≤0.05) dose dependant reduction in cell viability along with a dose dependant
enhancement of lactate dehydrogenase release. However when the cells were treated with a combination of docosahexaenoic
acid at varying concentrations (50, 75, 100, 125 and 150 μM), the above mentioned conditions were found to be
reversed in Pre-treatment and Co-treatment experiments, but not in Post treatment. The most effective combination was
found to be 10 μM arsenic trioxide with 100 μM of docosahexaenoic acid in both Pre-treatment and Co- treatment studies.
Thus the preliminary assays of our study showed that docosahexaenoic acid administration as Pre-treatment or
Co-treatment can aid in reducing arsenic trioxide induced hepatotoxicity. Further studies are required to elucidate the mechanisms
behind the protective effects.
Key Words– Arsenic trioxide, hepatotoxicity, docosahexaenoic acid, cell damage
The aim of the study was to investigate the damage created in tissue by using an in vivo isolated portal ischemia and reperfusion model in the rat liver and the effects of heparin administration on the complement system. A total of 25 male rats weighing 150-290 gr were used in the study. Following anesthesia with ketamine hydrochloride and xylazine hydrochloride, the incision area was shaved in all rats except the control group. The portal vein was isolated and clamped, and ischemia and reperfusion created. Two groups were sacrificed at the 24th hour and two at the 48th hour. Heparin was administered to one of the groups sacrificed at the 24th hour and not to the other group, and similarly one of the groups sacrificed at the 48th hour received heparin while the other did not. Biochemical and pathologic parameters were used to evaluate the damage using serum and liver tissue samples from the sacrificed rats. We used the liver GSH, MPO and C3 levels and the serum IL-6 level to evaluate the ischemia and reperfusion damage in the liver tissue. Heparin was shown to decrease the damage occurring after ischemia and reperfusion by decreasing complement activation and the MPO and IL-6 levels while increasing GSH levels as a result of the statistical analysis performed. Heparin was shown to prevent tissue damage after ischemia and reperfusion by decreasing complement activation and inflammation.
ABSTRACT- The present study was conducted to investigate the effect of cadmium chloride on Histoarchiteceture of head kidney of fresh water fish Heteropneustes fossilis. The fishes were exposed to 0.5 ppm of cadmium chloride for 21 days. The most remarkable changes in head kidney, due to cadmium chloride were lysed condition of interrenal and chromaffin cells. The traces of cytoplasm had dark brown to black coloured cytoplasm. Most of cells are deformed and necrotic condition. Their size was significant at (P< 0.01 and 0.001) increased after cadmium chloride. All these changes will be recovered by herbal compound i.e. Ashwagandha. The damaged tissues were recovered in already treated group.
Key-words- Ashwagandha, Cadmium chloride, Chromaffin cells, Heteropneustes fossilis, Histopathology, Interrenal cells
Biochemical and Toxicological Investigations of 5-Fluorouracil, Nimesulide, a...BRNSS Publication Hub
The objective of this study was biochemical and toxicological investigations of 5-fluorouracil (5-FU), nimesulide, and ascorbic acid (Vitamin C) in Wistar rats with hepatocellular carcinoma in. Results showed that DENA increased the level of alpha fetoprotein (AFP), alkaline phosphatase (ALP), serum glutamic oxaloacetate transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), and total bilirubin which was decreased by the various combinations of 5-FU to normal. On the other hand, DENA resulted in decrease of blood glucose level, DFN decreased more than DF, and DFC showed results similar to DFN, while DFNC led to increased AFP, ALP, SGOT, SGPT, and total bilirubin levels to normal. Histopathological evaluations showed normal architecture of tissues of rat liver in normal group. Lesser damage of hepatocytes and low index of necrosis were in pre- and post-treated group of 5-FU+DF, DFN+DFC groups. DFNC treated group exhibited histological features resembling normal control animals.
Hepatoprotective Effect of Cestrum parqui L. aerial parts and Phytochemical ...Jing Zang
This study deals with the investigation of hepatoprotective effect of 70% methanolic extract from Cestrum parqui aerial parts and determination of the bioactive components of the plant. The hepatoprotective effect of Cestrum parqui methanol extract (100, 500, 1000 mg/kg) was analysed on carbon tetrachloride (CCl4)-induced acute liver injury. The administration of a single dose of 40% CCl4 (1ml/kg b.w.) causes an increase in the activities of serum alanine aminotransferase (ALT) and aspirate aminotransferase (AST) enzymes and so pretreated orally of a dose from Cestrum parqui methanol extract (100, 500, 1000 mg/kg) and silymarin (200 mg/kg) for three consecutive days prior to The administration of a single dose of CCl4 significantly prevented the increase in the activities of these enzymes. Histological analysis showed that Cestrum parqui methanol extract at doses of 500 and 1000 mg/kg and silymarin reduced the incidence of liver lesions including vacuole formation, neutrophil infiltration and necrosis of hepatocytes induced by CCl4. The extract cause a negative result on the antioxidative enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRd) and decreased malondialdehyde (MDA) level in liver, as compared to those in the CCl4-treated group and this suggests that the hepatoprotective activity of the extract is due to the antioxidant effect of the extract. Phytochemical analysis of the methanol extract from Cestrum parqui aerial parts showed that it contained different phytoconstituents, flavonoids, tannins, saponins, alkaloids, terpenes and carbohydrates.
Ciprofloxacin resideu and their impact on Biomolecules n eggs of laying hens ...Sayed Koushik Ahamed
I have done this research on eggs for the welfare of mankind now i want to share my article for social awareness. I hope it will helps all researchers for their future further research.
Thank You
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
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Nicotine, the core addictive component presents in a substantial quantity in tobacco. Addiction of nicotine in female populations especially who belong to lower socio-economic status causes many adverse effects, like inducing oxidative stress, genotoxicity and disrupting immune response in the body. The investigation was designed to determine fi rst time the improved effi cacy of nanocurcumin against aggravated nicotine-induced toxicity on female system.
Similar to Prophylactic role of coenzyme Q10 and Cynara scolymus L on doxorubicin-induced toxicity in rats: Biochemical and immunohistochemical study (20)
Ameliorative potential of the quercetin on lead-induced testicular damage mor...Prof. Hesham N. Mustafa
Background
Quercetin, a naturally occurring flavonoid known for its potent antioxidant properties, has been investigated for its potential in counteracting the harmful effects of lead (Pb) toxicity, which induces apoptosis and oxidative damage in various human tissues. This study aims to assess the reparative effects of quercetin on lead-induced testicular damage.
Methods
Four groups, each comprising ten adult male albino rats, were randomly assigned as follows: Quercetin group, Pb group, Pb + Quercetin group, and control group. All treatments were administered orally via gavage daily for a duration of 30 days. Evaluation of sex hormone levels (serum testosterone, FSH, and LH), cytokines and inflammatory mediators (IL-1β, TNF-α, MCP-1), lead concentration, oxidative and antioxidant stress markers (superoxide anion [O2−], MDA, SOD, CAT, GSH), and sperm characteristics were carried out.
Results
The results demonstrated a significant decline in sex hormones and antioxidants, accompanied by an increase in lead concentrations, cytokines, inflammatory mediators, and oxidative stress indicators (O2−, MDA), while SOD, CAT, and GSH levels were reduced. The Pb-intoxicated group exhibited a substantial increase in dead and abnormal sperm, along with significant reductions in sperm concentration and motility. Morphometrically, a marked decrease was observed in spermatogonia, primary spermatocytes, spermatids, and sertoli cells per seminiferous tubule, as well as epithelial height. Furthermore, coadministration of quercetin exhibited notable benefits. It significantly elevated testosterone levels (P < 0.001), testicular SOD, CAT, and GSH activities, while decreasing MDA levels (P < 0.001). Quercetin also mitigated the deleterious effects of lead toxicity on sperm parameters and restored morphometric variations, including epithelial height.
Conclusions
Quercetin supplementation alongside lead exposure showed a potential for ameliorating degenerative changes caused by lead toxicity in the testicles. This cotreatment effectively reduced oxidative stress, cytokine levels, inflammatory mediators, and restored biochemical alterations, thereby improving morphometric parameters.
The pattern of branching and intercommunications of the musculocutaneous nerv...Prof. Hesham N. Mustafa
Background:
The aim of the present work was to provide evidence about the anatomical variations as regard the origin, distribution, and branching pattern of the musculocutaneous nerve (MCN).
Materials and methods:
Brachial plexus was dissected in 40 upper limbs of 20 male adult cadavers. The pattern of the musculocutaneous nerve was photographed by a digital camera.
Results:
The location and length of the nerve branches between left and right arms were recorded and statistically analyzed. In (90%) of specimens the MCN originates from the lateral cord of the brachial plexus, in (5%) it arose from the median nerve (MN), while in the remaining (5%) specimen, it was absent. The musculocutaneous nerve pierced the coracobrachialis muscle in 90% of specimens, and in the remaining (10%) did not pierce it. The motor branches to biceps brachii muscle were categorized into: Type 1 (90%): one branch that divides to supply the two heads of biceps; Type 2 (5%): double branches, innervating each head of biceps separately. The motor branches to brachialis muscle were categorized into: Type 1 (82.9%): one branch; Type 2 (14.2%): double branches and Type 3 (2.9%): three branches that innervating brachialis muscle. Communications between the MCN and the MN were observed in 35% of specimens.
Conclusions:
The knowledge of the common and uncommon musculocutaneous nerve variations is important especially to the surgeons for carrying out surgical procedures in axilla and arm.
Morphohistometric analysis of the effects of Coriandrum sativum on cortical a...Prof. Hesham N. Mustafa
Objective: Natural compounds can act as metal chelators and oxygen free radical scavengers, which allows them to be used as bioactive antagonists to heavy metals neurotoxicity. The aim of the study to analyze the morphometric effects of Coriandrum sativum (C. sativum) on lead-induced neurotoxicity.
Materials and Methods: Forty Sprague-Dawley albino rats were divided into four equal groups (ten in each group): control group; coriander group: received aqueous C. sativum extracts (600 mg/kg BW for 60 days orally); lead (Pb) group: received a daily dose of lead acetate (Pb) (10 mg/kg BW for 60 days orally); Pb+ coriandrum group: received: aqueous C. sativum extract (600 mg/kg BW) prior to 10 mg/kg BW of Pb. The following parameters malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured. Layers thickness and nuclei density were analyzed.
Results: Lead levels in blood and tissues were decreased significantly in the Pb group and those findings were corrected significantly (p=0.001) with C. sativum addition. Data exhibited an increase in oxidative stress marker MDA and a decrease in antioxidant enzymes activities (SOD, CAT, and GPx) significantly in the Pb group and those effects were reversed significantly (p=0.001) by C. sativum administration. The cerebellar cortex and all layers of the somatosensory cortex thickness and nuclei density were diminished significantly in the Pb group. The morphometrical measurements were corrected significantly (p=0.001) by C. sativum.
Conclusion: From the findings of the current study, Pb caused noticeable structural and functional variations in the cerebellar cortex and somatosensory cortex. C. sativum corrected these parameters as it possesses chelating and antioxidant potentials.
Background:
The anterolateral ligament (ALL) is a true well-defined ligament in the knee first described in 1879 by Segond. After the work of Claes et al., several studies were conducted about biomechanics and its role in stability of the knee. The anatomical existence of the ALL has been studied by and various radiographic diagnostic modalities and in cadavers. It originates from lateral femoral epicondyle and is inserted between Gerdy’s tubercle and the fibular head. There has been controversy about the existence of ALL in pediatric patients. The aim of this work was to confirm the presence of ALL in pediatric patients by using MRI.
Materials and Methods:
We reviewed the knee MRI scans of 100 pediatric patients (ages between one and 12 yr) who had no knee injury or congenital deformity and had been evaluated by an expert radiologist.
Results:
The ALL was detected in 90% of the pediatric patients with the use of MRI.
Conclusions:
The main finding of this study was that ALL can be seen in pediatric patients using MRI. Despite numerous studies, additional research is needed to further define the role of the ALL in knee function.
Level of Evidence:
Level IV.
Protective effect of garlic extract against maternal and fetal cerebellar dam...Prof. Hesham N. Mustafa
Background: In spite of its industrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including neurotoxicity especially to the developing and young offspring. Recently, the utilisation of herbal plants has received a significant attention where there has been rising awareness in their therapeutic use; among these is the garlic. In light of the above, the current study is designed experimentally in female pregnant rats in order to investigate the beneficial role of garlic extract in the protection from the maternal and foetal cerebellar damage produced by administration of different doses of Pb during pregnancy.
Materials and methods: Positively pregnant female rats were divided into five groups; one control group, two Pb-treated groups (exposed to 160 and 320 mg/kg b.w. of Pb, respectively) and two groups treated with both Pb and garlic (exposed to Pb as previous groups together with 250 mg/kg b.w./day of garlic extract). Treatments started from day 1 to day 20 of pregnancy, where the mother rats of different experimental groups were sacrificed to obtain the foetuses. Pb level in the maternal and foetal blood and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of different mother and foetal groups were processed to histological and immunohistochemical staining for microscopic examination.
Results: The results showed that administration of Pb to pregnant rats resulted in a dose-dependent toxicity for both mothers and foetuses in the form of decrease in maternal weight gain, placental and foetal weights, brain weight and diminished foetal growth parameters, which were prominent in rat's group treated with larger dose of Pb. In Pb-treated rats, Pb level in blood and cerebellum was high when compared with the control group. The histopathological examination of the cerebellum of treated dams and foetuses showed marked alterations mainly in the form of Purkinje cell degeneration and lack of development of foetal cerebellum. Co-treatment of garlic extract along with Pb resulted in a significant decrease in Pb levels as compared with those treated with Pb alone with improvement of the histopathological changes.
Conclusions: This study was useful in evaluating the hazardous effects of uncontrolled use of Pb in general and in assessing the developmental and neurotoxicity of foetuses due to exposure during pregnancy in particular. Co-administration of garlic has beneficial effects in amelioration of Pb-induced neurotoxicity and reversing the histopathological changes of the cerebellum of mother rats and foetuses. (Folia Morphol 2018; 77, 1: 1-15).
Keywords: Purkinje cells; garlic; glial fibrillary acidic protein; lead.
Protective role of co q10 or l carnitine on the integrity of the myocardium i...Prof. Hesham N. Mustafa
Doxorubicin (DOX) is a chemotherapeutic agent used for treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10mg/kg); CoQ10 group (200mg/kg); L-carnitine group (100mg/kg); DOX+CoQ10 group; DOX+L-carnitine group. CoQ10 and L-carnitine treatment orally started 5days before a single dose of 10mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for 10days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed a noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1 β), tumor necrosis factor alpha (TNF-α), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With a visible improvements in α-SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.
Keywords: Cardiotoxicity; CoQ10 and L-carnitine; Dox; Vimentin; eNOS.
One year mortality rate after hip fracture in the western region of saudi ara...Prof. Hesham N. Mustafa
Background:
The mortality rate of elderly patients who sustain a hip fracture is high compared to the general population. Identifying risk factors can help predict patients at risk of hip fracture to reduce the mortality rate. No studies have shown the mortality rate of patients with hip fractures in the western region of Saudi Arabia. Therefore, this study aimed to identify the risk factors associated with the mortality of patients with hip fractures admitted to the King Abdulaziz Hospital and compare the results with other studies.
Methods:
The mortality rate (within 1 yr or less) in 177 patients over the age of 60 yr who were admitted to the university hospital between July, 2007, and September, 2012, with hip fractures was retrospectively studied. The patients were assessed with regard to gender, age, type of hip fracture, and type of surgical intervention.
Results:
The overall mortality rate 1 yr after hip fracture was 12.43%, and the mean age was 77.77 yr old. The risk factors most associated with mortality were as follows: advanced age (71 to 80 and 81 to 90 yr old), male, peritrochanteric (extracapsular) fracture, and operative fixation with dynamic hip screw.
Conclusions:
The mortality rate of patients with hip fractures within 1 yr has a high-risk potential, especially for male patients over 71 yr of age with peritrochanteric (extracapsular) fractures. Surgical treatment with dynamic hip screw also was shown to be a risk factor between the different treatment options.
Level of Evidence:
Level IV.
Biomarkers of Systemic Lupus Erythematosus and Systemic Sclerosis diseases ac...Prof. Hesham N. Mustafa
Systemic Lupus Erythematosus (SLE) and systemic sclerosis (SSc) are systemic inflammatory autoimmune disorders characterized by a large spectrum of clinical and laboratory features. The aim of the present study was to investigate the possible use of serum level of soluble intercellular adhesion molecule-1(sICAM-1) and soluble interleukin-2 receptor (sIL-2Ra) as biomarkers for monitoring of SLE and SSc disease activity. Moreover, it aimed to compare the specificity and sensitivity as well as cut-off value of both biomarkers in a sample of Egyptian patients. 50 SLE patients, 30 SSc patients and 60 age and sex matched healthy controls were enrolled in our study. sICAM-1and sIL-2Ra were measured in serum samples obtained from all participants. In addition to Erythosedimentation rate (ESR), complete blood count (CBC), Antineuclearantibodies (ANA) estimation, disease activity of both diseases were also assessed. sICAM-1and sIL-2Ra levels were higher in SLE and SSc patients versus control. Both parameters are correlated with each other as well as the activity parameters. A cut-off levels of 455.59 (ng/ml) &2525935 (pg/ml) in both SLE & SSs respectively was observed with the highest specificity and sensitivity. It could be concluded that sICAM-1 and sIL-2Ra are noninvasive biomarkers for SLE and SSc that could play a pathophysiologic role in development and progression of both diseases. Moreover, sICAM-1 and sIL-2Ra are correlated with the disease activity at cut-off values of 455.59 (ng/ml) & 2525935(pg/ml) respectively.
Morphohistometric study of the ligamentum flavum in cervical,thoracic and lum...Prof. Hesham N. Mustafa
ABSTRACT Anatomic characterization and fine structure of the human ligamentum flavum (LF), especially at different spinal levels, represent an attractive focus for the scientific and surgical application. Descrip-tive anatomical and structural study of LF at the cervical, thoracic and lumbar levels of the vertebral column in human cadavers is carried out here. The aim of the work is to clarify the anatomical features and fine structural differences in the human LF at different vertebral levels (cervical, thoracic and lumbar). Specimens of vertebral column were ob-tained from 34 human preserved cadavers. Their average age ranged between 56 and 69 years. Morphometric parameters including height, width and thickness of the ligament flavum at the mid-levels of cervical, thoracic and lumbar regions were measured. Sections obtained from different levels were stained with different stains. Morpho-metric measurements involved the relative elastic area, relative collagen area, elastic area% and collagen area% were measured.The results of the height, width and thickness of the LF at different spinal levels showed gradual increase in their mean values respectively. The LF midline gaps were found in the cervical, thoracic and lumbar regions. The morphometrical measure-ments showed that the average elastic area was highest in the cervical region and lowest in the tho-racic region. In the lumbar region, the percentages of both elastic area and the collagen area were nearly the same. The characterization of morpho-logical and histological aspects of the LF at differ-ent spinal levels will be of great importance for ap-plications in spinal surgery, biomechanical and physical rehabilitation of vertebral column.Keywords: Ligamentum Flavum – Spinal – Collagen and elastic fibers
Correlation between acl injury and involvement of the anterolateral ligament ...Prof. Hesham N. Mustafa
Background:
Clinical testing has demonstrated the role of the anterolateral ligament (ALL) in controlling anterolateral laxity and knee instability at high angles of flexion. Few studies have discussed the association between an anterior cruciate ligament (ACL) injury and ALL injury, specifically after residual internal rotation and a post-ACL reconstruction positive pivot-shift that could be attributed to ALL injury. The goal of this study was to assess the correlation between ALL injury and ALL injury with concomitant ACL injury using MRI.
Material and Methods:
This was a retrospective study of 246 patients with unilateral ACL knee injuries from a database that was reexamined to identify whether ALL injuries occurred in association with ACL injuries. We excluded the postoperative reconstructed cases. The charts were reviewed on the basis of the presence or absence of diagnosed ACL injury with no regard for age or sex.
Results:
Of the 246 patients with ACL injury, there were 165 (67.1%) patients with complete tears, 55 (22.4%) with partial tears, and 26 (10.6%) with sprains. There were 176 (71.5%) patients with ALL and associated ACL injuries, whereas 70 (28.5%) did not have associated ACL injuries. There was a significant statistical relationship between ACL and ALL injuries (P<0.0001).
Conclusions:
There is high incidence of ALL tears associated with ACL injuries. Clinicians should be aware of this injury and consider the possibility of simultaneous ALL and ACL repair to prevent further knee instability.
Level of Evidence:
Level IV.
Liver ischemia/reperfusion injury, a setting in which the functional mass is ...Prof. Hesham N. Mustafa
Liver ischemia reperfusion is induced during sur-gical procedures like liver transplantation and re-section. Multiple mechanisms have been postulat-ed to liver damage following liver ischemia reperfu-sion injury, such as oxidative stress and inflamma-tory reactions. The present study declares the pos-sible mechanism of tadalafil, toward modulating the inflammatory response. Forty-eight rats were divided into 4 groups as follows; Sham group sub-jected to midline laparotomy only. Tadalafil group administered Tadalafil 10 mg/kg intraperitoneal 45 min before sham operation. I/R (Ischemia-reperfusion) group, rats undergo 60 min of hepatic ischemia followed by 60 min of reperfusion. Tada-lafil + I/R group rats undergo a similar pattern of I/R after the treatment with Tadalafil 10 mg/kg, 45 min before ischemia. At the end of the reperfusion, the blood samples were collected for estimation of biochemical markers including liver enzymes using colorimetric assay method and serum: TNF-α (tumor necrosis factor-α), IL-6 (interleukin 6) le-vels, ICAM- 1 (Intercellular Adhesion Molecule-1) were measured. Tissues were evaluated by semi-quantitative and morphometrical approaches. Ta-dalafil succeeded in restoring normal levels of liverenzymes and ameliorating the oxidative stress as evidenced by decreasing MDA and restoring redu-ced glutathione levels in liver tissue homogenate. Also, Tadalafil exhibits anti-inflammatory effects, as it significantly decreased the levels of TNF-α, IL6 and ICAM-1. The findings are supported by BCL-2, TNF-α immunomarkers. It is concluded that modulation of the inflammatory response might be one of the mechanisms of Tadalafil-mediated he-patoprotection, so it is recommended as an adju-vant therapy in liver surgery.Keywords: Ischemia/reperfusion injury – Oxidative stress – Apoptosis – TNF-α – BCL-2
Neuro-amelioration of cinnamaldehyde in aluminum-induced Alzheimer’s disease ...Prof. Hesham N. Mustafa
Aluminum (Al) is a neurotoxic substance which has played an important role in the etiology, pathogenesis, and development of amyloid-β (Aβ) plaques. This study was carried out to evaluate the neuroprotective effect of aqueous cinnamon extract against aluminum chloride (AlCl3)-induced Alzheimer’s disease. Forty adult male albino rats, randomly divided into four equal groups. Control group; ACE200 group administered aqueous cinnamon extract (ACE) orally; AlCl3 group received daily intraperitoneal (i.p.) injection of AlCl3 for 60 days to induce neurotoxicity and AlCl3 + ACE200 group received a combination of AlCl3 and ACE in the same dose and route as previous groups. Aluminum administration significantly enhanced the memory impairment and the Aβ formation in the rat model. The cerebellum exhibited a significant reduced number of Purkinje cells, marked decrease in the density of dendritic arborization and prominent perineuronal spaces in the molecular layer. There was loss of dendritic spines, neurofibrillary degeneration, and appearance of neuritic plaques. Concomitant administration of AlCl3 and ACE displayed an observable protection against these changes with progressive improvement in memory and intellectual performance. In conclusion, ACE may play a protective role against formation of amyloid-β plaques in cerebellum.
Analytical Study of Clinicopathological Data of Saudi Patients with Osteoarth...Prof. Hesham N. Mustafa
SUMMARY: Knee osteoarthritis (OA) is a common disabling disease. Epidemiological studies have revealed various risk
factors for OA, including sex, aging, obesity, occupational illnesses, and chronic diseases. Here we evaluate the clinical, pathological,
and radiological findings of knee OA in a subset of Saudi patients who were subjected to total knee replacement (TKA). The study
population included 30 Saudi patients with knee OA who were operated by TKA (from June 2014 to December 2015) in the Department
of Orthopedics, Faculty of Medicine, King Abdulaziz University, Saudi Arabia. Patient’s clinical and radiological data were collected
from the hospital files. Pathological examination of the excised superior articular surface of tibia and femoral condyles were done.
Pearson Chi-squared analysis was used to test for differences between the variables in associated risk factors. There were more women
than men. Sixty per cent of patients were older than 60 years [mean age, 59.2 (females) and 61.7 (men) years-old]. All patients exceeded
obesity class 1, with females being more obese than males. Pathological examination of the superior articular surface of tibia and femoral
condyles showed high score lesions, which was more apparent in females than in males. Radiological findings showed that most lesions
were high grade. The findings of this study will help to understand the pathogenesis of OA and improve treatment decision making
relevant to TKA in knee OA in Saudi Arabia and elsewhere.
KEY WORDS: Osteoarthritis; Knee; Arthroplasty.
A Study on the Toxic Effect of Different Doses of Diclofenac Sodium on the De...Prof. Hesham N. Mustafa
SUMMARY: The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by
morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and
divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9
mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring’s from 0-7 days after birth
were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin
and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels,
increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group.
Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects
that are dose-dependent in the prenatal subjected kidney to this drug.
KEY WORDS: Diclofenac sodium; Proximal convoluted tubules; Apoptosis;Cyclooxygenase.
Thymoquinone ameliorates oxidative damage and histopathological changes of de...Prof. Hesham N. Mustafa
ABSTRACT
Lead (Pb) toxicity is known to be a chief environmental health issue, especially for pregnant
women and young children. Today, the use of medicinal herbs in the treatment of many diseases
and different toxic agents has become highly accepted due to their effectiveness and lower costs.
Thymoquinone (TQ), which is extracted from Nigella sativa seeds, is a potent antioxidant and anti
inflammatory agent. This study was designed to explore the optional protectivity of TQ against
maternal and fetal oxidative stress and brain damage induced by Pb administration. Pregnant
rats were distributed into seven groups: control group, TQ group, DMSO group, two groups Pb
treated (160 and 320 ppm), and two groups Pb-treated (160 and 320 ppm) co-treated with TQ.
Administration started from gestation day 1 (GD1) to day 20 (GD20) through oral gavage once
daily. Lead administration caused a dose-dependent toxicity for both mothers and fetuses. Also,
the histopathological assessment of the brains from Pb-treated groups showed marked altera
tions. Co-treatment of with TQ and Pb caused a significant decrease in Pb levels as compared
with those treated with Pb alone and amelioration of histopathological changes in the brains. It
was concluded that co-treatment of TQ along with gestational Pb exposure could mitigate the
effects against Pb-induced maternal and fetal neurotoxicity.
KEYWORDS
Lead; oxidative stress; brain;
Thymoquinone; fetal toxicity
A study on the toxic effect of different doses of Diclofenac sodium on the de...Prof. Hesham N. Mustafa
The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9 mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring’s from 0-7 days after birth were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels, increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group. Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects that are dose-dependent in the prenatal subjected kidney to this drug.
Keywords : Diclofenac sodium; Proximal convoluted tubules; Apoptosis; Cyclooxygenase.
Zingiber Officinale Alleviates Maternal and Fetal Hepatorenal Toxicity Induce...Prof. Hesham N. Mustafa
This study was designed to address the protective effects of Zingiber officinale on the toxic outcomes of prenatal Cadmium administration on pregnancy outcome. Pregnant female Sprague-Dawley rats were randomly divided into four groups (eight rats/each), control group received distilled water, 2nd group treated with 8.8 mg of CdCl2/kg b. wt, 3rd group treated with 250 mg of Zingiber officinale/kg b. wt, and 4th group treated with 250 mg of Zingiber officinale/kg b. wt, followed by 8.8 mg of CdCl2/kg b.wt. Daily body weight of pregnant was recorded from GD1-GD20, and then pregnant rats were sacrificed at GD20. Samples of maternal and fetal livers and kidneys were processed for histological examination. Administration of Cd to pregnant rats showed adverse effects on pregnant mothers and their fetuses; reduced maternal weight gain, reduced absolute organ weights, reduced fetal growth parameters and placental weights together with altered histological appearance of the maternal and fetal livers and kidneys. While co-administration of Zingiber officinale showed an improvement of these toxic alterations. Zingiber officinale through its antioxidant activity could be beneficial against toxic outcomes of Cd exposure during pregnancy.
Evaluation of the safety of conventional lighting replacement by artificial d...Prof. Hesham N. Mustafa
Background
Short morning exposure to high illuminance visible electromagnetic radiations termed as artificial daylight is beneficial for the mental health of people living in geographical areas with important seasonal changes in daylight illuminance. However, the commercial success of high illuminance light sources has raised the question of the safety of long hour exposure.
Methods
We have investigated the effect of the replacement of natural daylight by artificial daylight in Swiss mice raised under natural lighting conditions. Mice were monitored for neurotoxicity and general health changes. They were submitted to a battery of conventional tests for mood, motor and cognitive functions’ assessment on exposure day (ED) 14 and ED20. Following sacrifice on ED21 due to marked signs of neurotoxicity, the expression of markers of inflammation and apoptosis was assessed in the entorhinal cortex and neurons were estimated in the hippocampal formation.
Results
Signs of severe cognitive and motor impairments, mood disorders, and hepatotoxicity were observed in animals exposed to artificial daylight on ED20, unlike on ED14 and unlike groups exposed to natural daylight or conventional lighting. Activated microglia and astrocytes were observed in the entorhinal cortex, as well as dead and dying neurons. Neuronal counts revealed massive neuronal loss in the hippocampal formation.
Conclusions
These results suggest that long hour exposure to high illuminance visible electromagnetic radiations induced severe alterations in brain function and general health in mice partly mediated by damages to the neocortex-entorhinal cortex-hippocampus axis. These findings raise caution over long hour use of high illuminance artificial light.
The Ameliorative Potential of Dexmedetomidine and Benincasa Cerifera Extract ...Prof. Hesham N. Mustafa
Renal ischemia/reperfusion injury (IRI) represents the main reason for acute kidney injury (AKI). Dexmedetomidine (Dex) and Benincasa cerifera (BC) have wide benefits due to their anti-inflammatory and antioxidant properties. This study aims to illustrate the protective effects of BC and Dex on renal IRI in a diabetic model. Sixty adult male albino rats (Wistar strain), weighing 250–300 g, were included in the study. The rats were divided into four groups, as follows: sham group: (non-diabetic); diabetes mellitus (DM) + IRI group: streptozotocin (STZ)-induced diabetic rats exposed to renal IRI on day 30 after diagnosis of diabetes; DM + IRI + BC group: STZ-induced diabetic rats treated with BC (500 mg/kg) for 30 days after diagnosis of diabetes, then exposed to renal IRI; and DM + IRI + Dex group: STZ-induced diabetic rats treated with Dex (100 µg/kg intraperitoneally) 5 min before induction of ischemia on day 30 after diagnosis of diabetes, then exposed to renal IRI. Biochemical parameters, histopathological examination, and immunohistochemical markers were evaluated. A significant improvement in the biochemical, histopathological, and immunohistochemical parameters were observed in the DM + IRI + BC group, while the DM + IRI + Dex group showed improvements in renal IRI and dyslipidemia. The present study demonstrated that oxidative stress plays a chief role in renal IRI in the STZ-induced diabetic model. Treatment with BC achieved excellent ameliorative effects, while treatment with DEX improved renal IRI.
Keywords:
Diabetes; Dexmedetomidine; Ischemia/Reperfusion; Oxidative Stress
Beneficial Effects of Curcumin Inmaternal and Fetal Oxidativestress and Brain...Prof. Hesham N. Mustafa
This study was planned to explore the protective role of curcumin (Cur) against maternal and fetal oxidative stress and cerebral damage induced by lead (Pb) during pregnancy. Positively pregnant female rats were divided into seven groups: control group, Cur group (300 mg/kg of Cur/b.wt.), DMSO group (50% DMSO), two Pb-treated groups (exposed to 160 and 320 mg/kg b.wt./day of Pb acetate, respectively), and two groups treated with both Pb and Cur (exposed to Pb as previous groups together with 300 mg/kg b.wt./day of Cur). Treatments through oral gavage once a day started from gestation day 1 (GD1) till day 20 (GD20), where the mother rats of different experimental groups were sacrificed to obtain the fetuses. Different chemical parameters were assessed. Brain specimens of mother and fetal groups were processed with examination. The results displayed that Pb administration to pregnant rats resulted in a dose-dependent toxicity for both mothers and fetuses. Also, there was a significant rise in lipid peroxidation and decreased antioxidant enzyme activities in the brains of the different Pb-treated groups. The histological examination of the brain of treated dams and fetuses showed marked alterations. Co-treatment of Cur along with Pb caused a significant decrease in Pb levels as compared with those treated with Pb alone, improving the oxidative condition with amelioration of the brain’s histopathological changes. Co-administration of Cur could have ameliorative effect against Pb-induced neurotoxicity through the reduction of oxidative stress and reversal of histopathological changes.
Keywords:
Lead; Oxidative Stress; Brain; curcumin; Fetal toxicity
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?
Prophylactic role of coenzyme Q10 and Cynara scolymus L on doxorubicin-induced toxicity in rats: Biochemical and immunohistochemical study
1. ISSN 0253-7613
INDIAN JOURNAL OF
PHARMACOLOGY
Website: www.ijp-online.com
Official Publication of the Indian Pharmacological Society
www.indianpharmacology.org
IndianJournalofPharmacology•Volume47•Issue6•November-December2015•Pages???
VOL. 47 | Issue 6 | November-December 2015VOL. 47 | Issue 6 | November-December 2015
3. 650 Indian Journal of Pharmacology | December 2015 | Vol 47 | Issue 6
Mustafa, et al.: Prophylactic of CoQ10 and Cynara scolymus L on doxorubicin
responsible for adenosine triphosphate synthesis.[5]
CoQ10 is
considered a potent lipophilic antioxidant; it acts directly with
free radicals or as a reducing agent for regenerating Vitamins E
and C from their oxidized forms.[6]
CoQ10 inhibits the generation
of reactive oxygen species and lipid peroxidation products
during free‑radical scavenging, suppresses excess nitric oxide
(NO) production, and prevents nitrative stress in tissues.[7]
In addition, CoQ10 exhibits anti‑inflammatory properties by
reducing the release of proinflammatory cytokines during
inflammatory injury.[8]
Cynara scolymus L. (CS) (artichoke) is rich in minerals,
phenolics, and fiber, and low in lipids. It is considered as
one of the most famous Mediterranean vegetables. It has
been used from ancient times in traditional medicines as a
diuretic.[9]
CS has antioxidant properties due to its content of
hydroxycinnamates and flavonoid glycosides.[10]
Various studies
are ongoing to evaluate the role of CS as a hepatoprotective
and anticarcinogenic plant.[9]
Proliferating cell nuclear antigen (PCNA) is a nuclear protein
that engages in the coordination of DNA replication and the
regulation of the cellular cycle.[11]
Studies have found that
PCNA protein can be used to quantitatively measuring hepatic
regenerative activity.[12]
In normal condition, hepatic stellate cells (HSCs) are
quiescent cells that generate an extracellular matrix
(ECM) in the space of Disse.[13]
HSCs perform a crucial
role in the pathogenesis of fibrosis by excessive deposition
of ECM materials.[14]
Furthermore, hepatic injury leads
to activation of HSCs, recognized by proliferation and
myofibroblastic transformation.[15]
Activated HSCs display a
strong immunoreactivity of cytoplasmic alpha‑smooth muscle
actin (α‑SMA).[14]
The aim of this study was to evaluate the possible
ameliorative potential of CoQ10 and CS on dox‑induced toxicity.
Materials and Methods
Animals and Treatment
Adult male albino Sprague‑Dawely rats, weighing 130–160 g,
10–12 weeks’ age, were obtained from the animal house of the
National Research Center, Giza, Egypt. The rats were subjected
to controlled conditions of temperature (25°C ± 3°C), humidity
(50–60%) and illumination (12‑h light, 12‑h dark cycle, lights
on at 08:00 h) and were provided with standard pellet diet and
water ad libitum for 1 week before starting the experiment.
All animal care and procedures were in accordance with the
European Communities Council Directive of November 24, 1986
(86/609/ECC) and the R.D. 223/1988 and were approved by
Ethics Committee of National Research Centre, Egypt. The rats
were exposed to dox (Pharmacia Italia Spa, Italy) and CoQ10
(Sigma Chemical Co., St Louis, Mo., USA), which was prepared
in a 1% aqueous solution of Tween 80; they were also exposed
to CS purchased from Biover (Bruges, Belgium), which was
prepared in a 1% aqueous solution of Tween 80.
The chemical composition of the CS leaf extract was
determined by analyzing its chlorogenic acid (CGA), cynarin,
and luteolin‑7‑O‑glucoside content in triplicate by an high
performance liquid chromatography (HPLC) method adapted
from European Pharmacopoeia.[8]
CS leaf extract (30 mg) was dissolved in 25 ml 30%
methanol. Calibration curves were composed for the three
standards (CGA, cynarin and luteolin‑7‑O‑glucoside). All
samples were analyzed on a Gilson HPLC system with ultraviolet
detector at wavelength 330 nm. As mobile phase, solvent A:
0.5% phosphoric acid in 5% methanol and solvent B: 0.5%
phosphoric acid in acetonitrile were used. The gradient profile
started with a linear increase of 5–25% B in 30 min, followed
by a 5 min linear increase to 100% B, after which the initial
conditions were reinstalled. A flow rate of 1.0 ml/min was
used. A Licrospher 100 C18 reversed‑phase analytical column
(250 mm × 4 mm, 5 µl) with a Licrospher guard column
(4 mm × 4 mm, 5 µm) from Merck (Germany) was used for
the separation of the phenolic compounds.
Experimental Design
Sixty rats were randomly allocated into six groups (10 rats
each). Groups were treated with the drugs as follows:
Group 1 received 1% aqueous solution of Tween 80 and
served as a normal control. Group 2 received dox (10 mg/kg,
single dose intraperitoneally [i.p.]) on the 6th
day and served as
positive control. Group 3 received CoQ10 (200 mg/kg) for 21 days.
Group 4 received CS (500 mg/kg) for 21 days. Group 5 received
CoQ10 (200 mg/kg) for 6 days, dox (10 mg/kg, single dose i.p.)
on the 6th
day and continued administration of CoQ10 until day
21. Group 6 received CS (500 mg/kg) for 6 days, dox (10 mg/kg,
single dose i.p.) on the 6th
day and continued administration of CS
day 21. On day 21, blood samples were collected, animals were
sacrificed, and organs (liver and kidney) were excised.
Serum and Tissue Preparation
Preparation of serum and tissue homogenates
All rats were sacrificed under anesthesia 24 h after the
last treatment and overnight fasting. Before sacrifice, blood
samples were collected from the retro‑orbital venous plexus.
These samples were kept at room temperature for 30 min and
centrifuged at 3000 rpm for 10 min. Serum samples obtained in
this way were aliquoted and stored in a freezer (−20°C) for use
in biochemical analyses that included aspartate transaminase
(AST), alanine transaminase (ALT), albumin, total protein, total
bilirubin, urea, and creatinine.
After sacrifice, the abdomen was opened wide and the
liver and kidneys were removed and washed 3 times with
cold physiological saline (0.9% NaCl). Then, the liver and
kidneys were weighed and part of them was homogenized for
the measurement of oxidative stress markers. Kidneys and
livers were homogenized (GlasCol homogenizer), and a 20%
w/v homogenate was prepared in ice‑cold phosphate buffer
(0.01 M, pH 7.4). The homogenate was centrifuged at 3000 rpm
for 20 min and the supernatant was then divided over several
containers to avoid sample thawing and refreezing, and was
kept at −80°C until analysis.
Serum parameters
Serum ALT and AST were determined using ELISA kits
supplied by the Bio Diagnostic Company (Cairo, Egypt). Serum
albumin, total protein, total bilirubin, urea, and creatinine were
determined by spectrophotometer using the corresponding
colorimetric kits supplied by Bio Diagnostic Company (Cairo,
Egypt).
4. 651Indian Journal of Pharmacology | December 2015 | Vol 47 | Issue 6
Mustafa, et al.: Prophylactic of CoQ10 and Cynara scolymus L on doxorubicin
Hepatic and renal oxidative markers
After homogenization, the supernatant was obtained
and used to determine malondialdehyde (MDA) and reduced
glutathione (GSH) levels in liver and kidney using colorimetric
assay kits in accordance with the manufacturer’s instructions
(Bio Diagnostic, Cairo, Egypt). NO levels were assayed in liver
and kidney using a colorimetric assay kit as directed by the
manufacturer (Cayman Chemical Co., USA).
Activities of antioxidant enzymes in liver tissue homogenate
The activities of antioxidant enzymes, such as catalase,
superoxide dismutase (SOD), and glutathione peroxidase (GPx),
in the liver tissue homogenates of all experimental groups were
measured using a Cayman (USA) assay kit in accordance with
the manufacturer’s instructions.
Histological examination
Liver samples were fixed in 10% neutral buffered formalin
and embedded in paraffin. All tissue samples were sectioned at
four µm and stained with hematoxylin and eosin and periodic
acid‑Schiff (PAS). For each specimen, at least three to five slides
were examined using an Olympus BX53 microscope equipped
with DP73 camera (Olympus, Tokyo, Japan).
Histopathological evaluation
The sections were analyzed for hepatocyte degeneration,
parenchymal necrosis, central vein congestion and thrombosis,
bile duct proliferation and leukocyte infiltrations. At the end of
the analyses, the findings were presented in a table in which the
degree of degeneration was scored. Score levels of 0, +1, +2,
+3 were equivalent to no, mild, moderate, and severe levels,
respectively. The scores represented values obtained from
tissue sections of six animals of each group, five fields/section.
Immunohistochemical examination
Using the streptavidine‑biotin‑peroxidase technique, the
endogenous peroxidase activity was eliminated using 10%
H2
O2
for 15 min. Sections were then incubated for 1 h with the
primary antibody against α‑SMA (a mouse monoclonal antibody;
Dako, Carpinteria, California, USA; dilution 1:50; cellular site
was cytoplasmic) as a marker of activated HSCs. They were
similarly incubated with the primary antibody against PCNA
(a mouse monoclonal antibody; Dako, Carpinteria, California,
USA; dilution 1:200; cellular site was nuclear) as a marker of
hepatocyte regeneration. All sections were counter‑stained with
Mayer’s hematoxylin. Negative control sections were prepared
by omitting the primary antibody. Positive control standard
laboratory slides were used for all stains to prove the success of
the technique. All slides were examined under light microscopy
at ×400 magnification and the presence of labelled cells was
documented. Absence of staining was recognized as a negative
result (−), while the presence of brown staining was recognized
as positive result (+).
Morphometry
Ten nonoverlapping fields for each animal at a magnification
of ×400 were selected indiscriminately and analyzed. The
measurements were done with the use of Image‑Pro Plus v6.0
(Media Cybernetics, Maryland, USA) and NIH ImageJ (v1.49)
(http://rsb.info.nih.gov/ij/) associated with an Olympus BX53
microscope. The area percentage of α‑SMA immunopositive
cells and the optical density (OD) of PCNA immunostaining was
evaluated. OD was estimated by the following formula:
OD = log (max intensity/mean intensity), where max
intensity = 255 for 8‑bit images.
Semithin sections
Liver samples of approximately 1 mm3
were obtained and
immersed in 2.5% glutaraldehyde in 0.1 M phosphate buffer
at 4°C for 3 h and postfixed in 1% osmium tetraoxide. After
dehydration in ascending grades of ethanol, the tissues were
embedded in Epon 812. Semithin sections were prepared from
the blocks, stained using toluidine blue, and observed with the
light microscope.
Statistical Analysis
The data analysis was carried out using the Statistical
Package for Social Science (SPSS software version 20,
Chicago, Illinois, USA). All numeric variables were expressed
as mean ± standard deviation. Statistical comparisons were
performed using the one‑way analysis of variance (ANOVA) test,
followed by post‑hoc least significant difference multigroup
comparison. Homogeneity of variance was assessed using the
one‑way ANOVA test and Levene’s statistic test. For all tests,
a probability (P < 0.05) was considered significant.
Results
Body Weights and Organ Weights
During the study, three cases of animal mortality in
dox‑treated group were recorded. No significant changes were
observed between the study groups and the control in terms of
food and water consumption or body weight gain/loss.
Biochemical Markers
This study showed deterioration of liver function in the
dox group, which was represented by significant elevation of
serum ALT, AST and total bilirubin in comparison to the control,
CoQ10 and CS groups regarding ALT (P = 0.000, P = 0.0001,
P = 0.001) while for AST and total bilirubin (P = 0.0001 for
all groups). Treatment with CoQ10 and CS led to significant
decrease in the serum levels of ALT, AST and total bilirubin
in comparison to the dox group (P = 0.0001 for all groups).
However, regarding total bilirubin levels still significantly
higher in treated groups with CoQ10 and CS in comparison to
the control group (P = 0.022; P = 0.03) respectively. Neither
CoQ10 nor CS alone, without dox treatment, had any effect on
these liver biomarkers compared to the control group [Table 1].
Moreover, dox group experienced significant decrease in
serum albumin and total protein in comparison to the control,
CoQ10 and CS groups (P = 0.0001 for all groups). Treatment
with CoQ10 and CS led to significant increase of both serum
albumin and total protein in the dox‑CoQ10 and dox‑CS groups,
as compared to the dox group (P = 0.0001 for all groups).
However, serum total protein levels still significantly higher in
treated groups with CoQ10 and CS in comparison to the control
group (P = 0.023; P = 0.03), respectively. Neither CoQ10 nor
CS alone, without dox treatment, had any effect on these liver
biomarkers compared to the control group [Table 1].
Inaddition,administrationofdoxresultedinthedeterioration
of kidney function, as shown by an increase in the serum levels
5. 652 Indian Journal of Pharmacology | December 2015 | Vol 47 | Issue 6
Mustafa, et al.: Prophylactic of CoQ10 and Cynara scolymus L on doxorubicin
of creatinine and urea in the dox group compared to the control,
CoQ10 and CS groups (P = 0.0001 for all groups). Treatment
with CoQ10 and CS led to a significant decrease in the serum
levels of creatinine and urea in the treated groups compared
to the dox group (P = 0.0001 for all groups). Serum creatinine
in both treated groups, however, were significantly higher than
the control groups (P = 0.007). Neither CoQ10 nor CS alone,
without dox treatment, had any effect on these two markers of
renal function compared to the control [Table 1].
As regard the oxidative biomarkers in liver, the results of
this study showed that the administration of dox increased
lipid peroxidation, as shown by a significant increase in the
level of MDA in the dox group compared to the control, CoQ10
and CS groups (P = 0.0001 for all groups). Administration
of CoQ10 and CS led to a significant decrease in the levels
of MDA in the treated groups (P = 0.0001 for all groups) but
still significantly higher when compared to the control groups
(P = 0.041; P = 0.0001), respectively [Table 2].
In addition, liver nitrate (NO) levels were increased
significantly in dox group compared to the control, CoQ10 and
CS groups (P = 0.0001, P = 0.001, P = 0.0001), respectively.
Treatment with CoQ10 and CS led to a significant decrease in the
levels of NO in the treated groups and their levels were higher
than the control group (P = 0.0001 for all groups) [Table 2].
Table 1:
Effect of CoQ10 and CS on serum levels of liver and kidney biomarkers in doxorubicin induced toxicity in rats
Variable Serum ALT
(U/mL)
Serum AST
(U/mL)
Serum
albumin (g/dL)
Serum total
protein (g/dL)
Serum total
bilirubin (mg/dL)
Creatinine
(mol/L)
Urea
(mmol/L)
Control 328.91±38.81 1008.63±180.78 4.26±0.98 6.14±1.09 0.29±0.10 24.00±3.74 26.00±3.39
Dox 542.73±12.18
0.000*
1367.75±157.01
0.0001*
1.25±0.88
0.0001*
2.23±0.98
0.0001*
0.83±0.08
0.0001*
56.00±4.18
0.0001*
46.40±3.78
0.0001*
CoQ10 319.09±63.61
0.650*
0.0001@
959.60±99.39
0.813*
0.0001@
3.72±1.02
0.229*
0.0001@
5.41±1.13
0.181*
0.0001@
0.32±0.10
0.797*
0.0001@
26.40±2.07
0.234*
0.0001@
26.00±2.92
1.000*
0.0001@
CS 340.73±15.33
0.586*
0.0001@
943.20±68.77
0.669*
0.0001@
3.84±0.78
0.347*
0.0001@
5.19±0.69
0.087*
0.0001@
0.35±0.05
0.562*
0.0001@
26.80±3.42
0.167*
0.0001@
26.40±2.30
0.904*
0.0001@
Dox + CoQ10 340.73±15.325
0.525*
0.0001@
985.00±127.6
0.952*
0.0001@
3.49±0.35
0.094*
0.0001@
4.88±0.45
0.028*
0.0001@
0.42±0.062
0.022*
0.0001@
29.6±1.48
0.007*
0.0001@
27.20±1.64
0.493*
0.0001@
Dox + CS 355.1909±20.39
0.231*
0.0001@
959.04±142.59
0.808*
0.0001@
3.67±0.350
0.188*
0.0001@
4.92±0.33
0.030*
0.0001@
0.41±0.094
0.03*
0.0001@
29.8±2.8
0.007*
0.0001@
27.60±1.52
0.363*
0.0001@
Data are expressed as mean±SD, *Significance versus control, @
Significance versus dox. Analysis was made using one‑way ANOVA (LSD). SD=Standard deviation,
LSD=Least significant difference, Dox=Doxorubicin, CS=Cynara scolymus L., CoQ10=Coenzyme Q10, ALT=Alanine transaminase, AST=Aspartate transaminase,
ANOVA=Analysis of variance
Table 2:
Comparison of serum levels of oxidative stress markers in the liver of the study groups versus control and dox groups
Variable Liver MDA
(nM/mg)
Liver NO
(uM/g)
Liver GSH
(uM/g)
Liver catalase
activity (U/g)
Liver SOD
(U/mL)
Liver GPx
(mU/mL)
Control 555.46±17.44 246.66±12.61 5.86±0.40 19.79±0.77 71.25±4.92 71.33±27.13
Dox 841.74±33.51
0.0001*
338.14±10.86
0.0001*
4.03±0.26
0.0001*
11.40±0.83
0.0001*
56.25±8.72
0.002*
38.91±14.50
0.040*
CoQ10 554.49±30.23
0.978*
0.0001@
270.60±21.18
0.186*
0.001@
5.44±0.40
0.367*
0.005@
18.79±2.78
0.251*
0.0001@
67.53±5.89
0.384*
0.018@
89.16±16.21
0.273*
0.004@
CS 557.53±10.58
0.953*
0.0001@
241.20±30.13
0.76*
0.0001@
5.88±0.35
0.969*
0.0001@
18.24±0.84
0.081*
0.0001@
63.44±4.83
0.075*
0.117@
81.06±18.72
0.546*
0.014@
Dox + CoQ10 630.13±35.40
0.041*
0.0001@
248.66±32.25
0.911*
0.0001@
6.18±1.35
0.497*
0.0001@
16.93±0.31
0.002*
0.0001@
65.03±6.65
0.117*
0.059@
97.27±26.47
0.115*
0.001@
Dox + CS 710.92±18.23
0.0001*
0.001@
236.91±9.03
0.586*
0.0001@
5.51±0.62
0.458*
0.003@
17.42±0.96
0.010*
0.0001@
64.06±5.53
0.100*
0.090@
77.81±29.00
0.669*
0.016@
Data are expressed as mean±SD, *Significance versus control, @
Significance versus dox. Analysis was made using one‑way ANOVA (LSD). SD=Standard deviation,
LSD=Least significant difference, Dox=Doxorubicin, CS=Cynara scolymus L., MDA=Malondialdehyde, NO=Nitric oxide, GSH=Glutathione, SOD=Superoxide dismutase,
GPx=Glutathione peroxidase, CoQ10=Coenzyme Q10, ANOVA=Analysis of variance
6. 653Indian Journal of Pharmacology | December 2015 | Vol 47 | Issue 6
Mustafa, et al.: Prophylactic of CoQ10 and Cynara scolymus L on doxorubicin
Moreover, administration of dox resulted in a significant
decrease in the level of reduced liver GSH and a significant
decrease in the activity of antioxidant enzymes in the liver,
including catalase and GPx, as compared to the control, CoQ10
and CS groups [Table 2].
Treatment with CoQ10 and CS led to an elevation of GSH
levels and an increase in the activity of antioxidant liver GPx to
normal levels, for GSH (P = 0.0001, P = 0.003), and for GPx
(P = 0. 0.001, P = 0.016), moreover treatment with CoQ10 and
CS led to significant elevation liver catalase levels compared to
dox group (P = 0.0001 for both groups); however, their levels
were still significantly higher than the control group (P = 0.002,
P = 0.01), while regarding SOD levels were increased in
treated groups but not reaching significant levels (P = 0.059,
P = 0.090) [Table 2].
Regarding the results of the oxidative biomarkers in the
kidney, the results of this study showed that the administration
of dox resulted in a significant increase in the levels of both MDA
and NO in the dox group compared to the control, CoQ10 and
CS groups for MDA (P = 0.007, P = 0.039, P = 0.013), while for
NO (P = 0.0001 for all groups), respectively. Administration of
CoQ10 and CS led to a significant decrease in the levels of both
MDA and NO in the treated groups compared to the dox group
for MDA (P = 0.038, P = 0.022), while for NO (P = 0.0001 for
all groups) [Table 3]. Moreover, administration of dox resulted
in a significant decrease in the levels of GSH compared to
the control, CoQ10 and CS groups (P = 0.004, P = 0.0001,
P = 0.013). Treatment with CoQ10 and CS led to a significant
increase in the levels of GSH in the treated groups compared
to the dox group (P = 0.003, P = 0.005) [Table 3].
Histological Results of Hematoxylin and Eosin and Periodic
Acid‑Schiff Stained Sections
In all treated groups, an apparent parenchymatous
degeneration and disseminated eosinophilic degeneration
were noticed, especially in the middle and central zones of the
hepatic lobules. Moreover, a noticeable vacuolar degeneration
with ballooning and pyknotic nuclei were observed in the treated
groups. Few necrosis were found in the examined groups and
some inflammatory infiltrations in the middle and central zones
were seen. The occurrence of hepatic changes was reduced
among the dox‑CoQ10 and dox‑CS groups and clearly apparent
in the group treated only with dox [Table 4].
Controls showed normal appearance with a strong PAS
positivity corresponding to the accumulation of glycogen. Those
exposed to CoQ10 and CS were similar to the control, while the
dox‑administered group showed reduced PAS positivity. Those
treated with dox and CoQ10 exhibited improvement in the
cellular damage, with visible PAS positivity. The group treated
with dox and CS exhibited a decrease the cellular damage, with
apparent PAS positivity [Table 4].
Immunoreaction to Alpha‑smooth Muscle Actin
Controls showed faint α‑SMA staining in the vascular
media, especially in those of the portal area [Figure 1a]. The dox
group showed positive α‑SMA immunoreactivity in the portal
vessels media, the periportal area and along the perisinusoidal
spaces [Figure 1b and e]. Sections treated with dox and CoQ10
showed mild α‑SMA immunoreactivity in the vascular media
[Figure 1c]. Sections treated with dox and CS showed mild α‑SMA
immunoreactivity observed in the vascular media [Figure 1d].
Immunoreaction to Proliferating Cell Nuclear Antigen
Controls showed moderate immunoreactivity in some
hepatocyte nuclei [Figure 2a]. The dox group showed weak
immunoreactivity in the hepatocyte nuclei [Figure 2b]. Sections
Table 3:
Comparison of oxidative stress markers in the kidney of the
study groups versus control and dox groups
Variable Kidney MDA
(nM/mg)
Kidney
NO (uM/g)
Kidney
GSH (uM/g)
Control 332.95±72.52 21.66±1.78 1.28±0.21
Dox 444.74±28.02
0.007*
38.00±2.72
0.0001*
0.99±0.05
0.004*
CoQ10 361.28±37.42
0.468*
0.039@
25.23±1.54
0.185*
0.0001@
1.41±0.19
0.148*
0.0001@
CS 342.44±70.03
0.807*
0.013@
23.69±5.08
0.447*
0.0001@
1.23±0.11
0.626*
0.013@
Dox + CoQ10 360.97±13.29
0.472*
0.038@
23.80±5.83
0.422*
0.0001@
1.28±0.09
0.965*
0.003@
Dox + CS 351.15±98.53
0.639*
0.022@
22.20±4.19
0.838*
0.0001@
1.26±0.10
0.896*
0.005@
Data are expressed as mean±SD, *Significance versus control, @
Significance versus dox. Analysis was made using one‑way ANOVA (LSD).
SD=Standard deviation, LSD=Least significant difference, Dox=Doxorubicin,
CS=Cynara scolymus L., MDA=Malondialdehyde, NO=Nitric oxide,
GSH=Glutathione, CoQ10=Coenzyme Q10, ANOVA=Analysis of variance
Table 4:
Histopathological findings in dox‑induced hepatotoxicity
Control Dox CoQ10 CS Dox and CoQ10 Dox and CS
Parenchymatous degeneration 0 +3 0 0 +1 +2
Eosinophilic degeneration 0 +3 0 0 +1 +2
Vacuolar degeneration 0 +3 0 0 +1 +2
Necrosis and apoptosis (pyknotic nuclei) 0 +3 (N) 0 0 +1 (A) +2 (A)
inflammatory infiltrations 0 +3 0 0 ± ±
PAS +3 +1 +3 +3 +2 +2
n=10, A=Apoptosis, N=Necrosis. Score of the positive PAS staining: Absence (0), few (+1), medium (+2) and high (+3). PAS=Periodic acid‑Schiff, Dox=Doxorubicin,
CoQ10=Coenzyme Q10, CS=Cynara scolymus L.
7. 654 Indian Journal of Pharmacology | December 2015 | Vol 47 | Issue 6
Mustafa, et al.: Prophylactic of CoQ10 and Cynara scolymus L on doxorubicin
treated with dox and CoQ10 showed intense immunoreactivity
in most of the hepatocyte nuclei [Figure 2c]. Sections treated
with dox and CS showed intense immunoreactivity in most of
the hepatocyte nuclei [Figure 2d].
Morphometric Results
The proportion of α‑SMA‑positive area in cells was
significantly higher in the groups treated with dox and either
CoQ10 or CS as compared to the dox group (P = 0.001,
P = 0.001) [Table 5]. Groups treated with dox and either CoQ10
or CS were significantly improved OD of PCNA expression as
compared to the dox group (P = 0.001, P = 0.001) [Table 5].
Toluidine Blue Stained Sections
Control group showed normal architecture [Figure 3a].
The dox group showed intensive vacuolar degeneration and
necrosis, and hepatocytes with abnormal metaphase chromatin
and dilated sinusoids [Figure 3b]. The dox‑CoQ10 groups
showed microvacuoles [Figure 3c], while the dox‑CS groups
showed variable‑sized vacuoles [Figure 3d].
Discussion
Endogenous CoQ10 is increased following dox treatment,
mightbeacellulardefenserelatedtoCoQ10geneexpression.[16]
In
this study, dox group showed a deterioration in liver parameters.
These results agreed with other study.[17]
Moreover, dox
elevates ALT because of lipid peroxidation and activation of
phospholipases.[16]
Dox decreased serum albumin and total
protein due to deterioration of liver synthetic functions resulting
from hepatocytes necrosis. Furthermore, total bilirubin rise
is due to partial bile duct obstruction because of hepatocytes
inflammation and fibrosis.[17]
In the present study, dox resulted in deterioration of renal
functions. This is explained by increased capillary permeability
and glomerular atrophy that resulted in albumin loss.[18]
Dox elevated oxidative stress markers that agreed with
others.[19]
Nitrosative stress produced by dox was consistent
with the finding that NO generation as inducible NOS form
was related to dox cytotoxicity.[18]
Dox administration
decreased GSH level. These results might lead to peroxidative
Table 5:
Area percentage of α‑SMA‑positive cells (means±SD) and PCNAOD
Control Dox Dox and
CoQ10
Dox and
CS
Area percentage
of α‑SMA
0.42±0.52 10.70±0.72
<0.001*
1.65±0.78
<0.01*
<0.001@
1.3±0.65
<0.05*
<0.001@
OD of PCNA 1.45±0.04 0.4±0.03
<0.001*
1.55±0.02
<0.001*
<0.001@
1.67±0.05
<0.001*
<0.001@
Data are expressed as mean±SD, *Significance versus control, @
Significance versus
dox. Analysis was made using one‑way ANOVA (LSD). SD=Standard deviation,
LSD=Least significant difference, Dox=Doxorubicin, CS=Cynara scolymus L.,
α‑SMA=Alpha‑smooth muscle actin, PCNA=Proliferating cell nuclear antigen,
OD=Optical density, ANOVA=Analysis of variance, CoQ10=Coenzyme Q10
Figure 1: (a) Control group showed faint immunoexpression. (b) Doxorubicin group showed positive immunoexpression. (c) Doxorubicin and
coenzyme Q10 showed mild expression. (d) Doxorubicin and Cynara scolymus showed mild expression. (e) Doxorubicin group showed positive
immunoreactivity of spindle‑shaped stromal cells (arrows) (alpha‑smooth muscle actin, scale bar = 20 µm)
b ca
d e
Figure 2: (a) Control group showed moderate immunoreactivity (arrows).
(b)Doxorubicingroupshowedminimalornoimmunoreactivityinthenuclei
(arrows). (c) Doxorubicin and coenzyme Q10 groups showed intense
expression (arrows). (d) Doxorubicin and Cynara scolymus groups
showed intense expression (proliferating cell nuclear antigen, scale
bar = 20 µm)
ba
c d
8. 655Indian Journal of Pharmacology | December 2015 | Vol 47 | Issue 6
Mustafa, et al.: Prophylactic of CoQ10 and Cynara scolymus L on doxorubicin
injury and destruction of cellular defense toward ROS.[20]
Dox administration decreased liver antioxidant enzymes.
That is attributed to free‑radical formation and oxidative
stress.[21]
Dox produces free radicals through transformation
into semiquinone, which reacts with molecular oxygen to form
superoxide radicals. And through an iron‑dox complex that is
effective in reducing oxygen to H2
O2
.[20]
In this study, co‑administration of CoQ10 and CS with dox
led to a decrease in oxidative stress. These results agreed with
other study by Heidarian and Rafieian‑Kopaei.[22]
Further, the
decrease in MDA was associated with increased concentrations
of reduced GSH, catalase activity and caspase 3 expression.[23]
The mechanisms whereby CoQ10 acts as an antioxidant
include removal of free radicals, such as lipid peroxyl and
alkoxyl radicals.[24]
In addition, NO bioactivity may be improved
by decreasing superoxide generation.[25]
It may be improved by
increasing the expression of mitochondrial uncoupling proteins;
this is an anti‑apoptotic effect that leads to a reduction in
free‑radical generation.[24]
CS has a high percentage of minerals
and polyphenolic compounds and inulin.[9]
The antioxidant effect
of CS is attributed to interference with the gene expression of
inflammatory pathways and the induction of antioxidant enzyme
synthesis, which results in oxidative stress reduction.[25]
In current work, dox histological changes are explained
by fatty infiltration[20]
and oxidative damage that leads to
mitochondrial DNA damage (mtDNA).[23]
Those changes might
attribute to DNA fragmentation and apoptosis initiation.[25]
Sinusoidal congestion might explain tissue damage and blood
coagulation.[24]
Disruption of sinusoidal wall integrity was
indicated by extravasation of erythrocytes in space of Disse.[18]
Hepatic fibrogenesisis initiated by hepatocytes injury, which
leads to inflammatory cells recruitment, activation of von
Kupffer cells and cytokines release.[17]
CoQ10 and CS protect against dox toxicity through
upregulating anti‑reactive oxygen species, prevention of
mtDNA injury, promotion of replication, suppression of
membrane‑active lipases, and defend the electron transport
chain.[12]
In the current study, increased PCNA expression by
administration of CoQ10 and CS with dox that is a consequence
to the ability of HSCs to engraft damaged cells.[15]
α‑SMA
expression observed in periportal tract refer to myofibroblasts.
The portal fibroblasts might be the source of myofibroblasts and
activated HSC.[14]
Apoptosis following the injury initiates HSCs
through a process mediated by Fas death receptor.[15]
Activated
HSCs proliferate and produce collagen through free‑radical
construction and activation of mitogen‑activated protein
kinase.[14]
The limitations of the study are the number of animals
that might be larger and the fixed dose of the dox that might
be variant to facilitate the statistical analysis and to broaden
the feedback. Furthermore, different doses of CoQ10 and CS
are advised. Quantitative measures as stereology and immune
Biomarkers of liver cells are recommended to support the
hypothesis of the study.
Conclusion
The present findings demonstrate that the renal toxicity and
hepatotoxicity induced by dox may be related to imbalance of
the oxidative stress. Moreover, pretreatment with CoQ10 and
CS effectively improve the toxic effects of dox in kidney and
liver, so that it was associated with up‑regulation of favorable
protective enzymes and down‑regulation of oxidative stress.
Overall, the study suggests that administration of CoQ10 and
CS limit renal and hepatotoxicity of dox.
Financial Support and Sponsorship
Nil.
Conflicts of Interest
There are no conflicts of interest.
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