This study examined the effects of chronic endurance exercise on doxorubicin (DOX)-induced damage in the thymus gland and thymocytes (T-cells). Rats were divided into groups that were sedentary or underwent treadmill training for 10 weeks, followed by injections of either saline or different doses of DOX. Three days later, thymic mass, viable T-cell count, and lipid peroxidation levels were analyzed. Chronic exercise decreased lipid peroxidation following DOX treatment but did not prevent reductions in thymic mass or T-cell numbers. This suggests that exercise elevates antioxidant defenses in the thymus to reduce oxidative stress from DOX, though it does not fully protect the
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- 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
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.
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- 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
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.
Comparison of the Hypazotemic Effects of Erythropoietin and U-74389G on Urea ...asclepiuspdfs
Aim: This study calculated the hypazotemic capacities of two drugs as follows: The erythropoietin (Epo) and the antioxidant drug U-74389G. The calculation was based on the results of two preliminary studies, each one of which estimated the hypazotemic influence, after the respective drug usage in an induced hypoxia-reoxygenation animal experiment. Materials and Methods: The two main experimental endpoints at which the blood urea levels were evaluated the 60th reoxygenation min (for the groups A, C, and E) and the 120th reoxygenation min (for the groups B, D, and F). Especially, the groups A and B were processed without drugs, groups C and D after Epo administration whereas groups E and F after U-74389G administration. Results: The first preliminary study of Epo presented a nonsignificant hypazotemic effect by 1.25% ± 1.67% (P = 0.4430). The second preliminary study of U-74389G presented a significant hypazotemic effect by 5.81% ± 1.57% (P = 0.0005). These two studies were co-evaluated since they came from the same experimental setting. The outcome of the co-evaluation was that U-74389G has 4.632148-fold more hypazotemic potency than Epo (P = 0.0000). Conclusions: The antioxidant capacities of U-74389G enhance the acute hypazotemic properties presenting 4.632148-fold more intensive hypazotemia than Epo (P = 0.0000).
Evaluation of hepatoprotective agents - Hemant KanaseHemant Kanase
1. Introduction
2. Hepatotoxicity: Mechanism
3. Therapeutic strategies available – their limitations
4. In vivo models of liver damage
- Non-invasive model
a. Chemically induced hepatotoxicity
b. Drug-induced hepatotoxicity
c. Radiation-induced hepatotoxicity
d. Metal-induced hepatotoxicity
e. Diet-induced hepatotoxicity
Models of Acute Hepatitis
Models of chronic hepatitis
Models of fibrosis
Models of cholestasis
Models of steatosis
4. Problems faced with animal studies
5. In vitro models of liver damage
6. Advantages and disadvantages of in vitro models
7. Parameters of evaluation
8. Clinical Assessment
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).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
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.
Objective: To study the effects of resveratrol in neuronal structures in traumatic brain injury (TBI).
Study Design: Thirty rats were categorized as (1) control group (n=10), saline solution administered i.p. for 14 days, (2) TBI group (n=10), trauma induced by weight-drop model on brain, and (3) TBI+Resveratrol group (n=10), 15 minutes after injury the rats were given resveratrol (10 μmoL/kg/i.p.) for 14 days. At the end of the experiment the cerebellum was excised for routine paraffin tissue protocol. Blood samples were tested for serum biochemical markers (MDA, SOD, CAT, and GSH-x).
Results: SOD, GPx, and CAT values were lowest in the TBI group. MDA and histological scores of dilations in vessels, inflammation, degeneration in neurons, apoptosis in microglia, ADAMTS8, and GFAP expressions were highest in the TBI group. Sections of the control group showed normal cerebellar histology. The trauma group showed degenerated ganglion layer, pyknotic and apoptotic Purkinje cell nuclei. Vascular thrombus was seen in the substantia alba and substantia grisea. In the Trauma+Resveratrol group, most pa- thologies observed in the TBI group were improved. In the control group, GFAP protein was expressed in granular cells, axons, dendrites, Purkinje cells, and microglia cells. In the trauma group, increased GFAP expression was observed in glial processes, neurons, and Purkinje cells. In the Trauma+Resveratrol group, GFAP was expressed in molecular layer and glial processes. In the control group, ADAMTS-4 activity was observed in granulosa layer, glial cells, and Purkinje cells. In the trauma group, ADAMTS-4 expression was positive in Purkinje cells and glial cells. In the Trauma+ Resveratrol group, ADAMTS-4 was expressed in Purkinje cells, granular cells, and glial cells.
Conclusion: GFAP and ADAMTS-4 proteins may be involved in regeneration of damaged astroglial cells and other glial cells, Purkinje cells, and synaptic extensions. We suggest that antioxidative drugs such as resveratrol may be alternative target agents in neurological disease.
Keywords: ADAMTS-4, brain, cerebellum, GFAP, rat, resveratrol, traumatic brain injury
Hepatoprotective Effect of Aqueous Extracts of Some Medicinal Plant Mixtures ...IOSRJPBS
The rhizomes of Ginger (Zingiberofficinale), Turmeric (Curcuma longa), Licorice (Glycyrrhizaglabra), the bark of Cinnamon tree,(Cinnamomumzeylanicum) and the calyces of red Roselle (Hibiscus sabdariffa L.)are herbs used in thishepatoprotective studies. This study evaluates the hepatoprotective activity of water extract mixtures using carbon tetrachloride (CCl4)-induced liver injury in rats.In vitroantioxidant activity of plant water extracts was determined using DPPH. The water extractmixtures wereadministered for 10 days; on the 10thday all rats were challenged with CCl4 except control group animals. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin levels were determined to prove the hepatoprotectiveeffect.The enzyme activities were significantly increased in CCl4 treated rats. The four water extract mixtures exhibited significant (P<0.05)><0.05) increased in all the water extract mixtures used.
Protective effects of commelina benghalensis linn (root) extract on ethanol i...IJSIT Editor
The present study was undertaken to investigate the protective effect and possible mechanism of
alcoholic (AlE) and aqueous extract (AqE) from Commelina benghalensis root (CB) on EtOH-induced hepatic
injury in Wistar rat. Hepatotoxic parameters studied in vivo include serum transaminases (AST, and ALT),
ALP, bilirubin, protein, lipid profile (Cholesterol, triglyceride, VLDL and HDL) and level of antioxidants
together with histopathological examination. Liv 52® was used as a reference hepatoprotective agent
(5ml/kg-1b.w.). AlE and AqE (200 mg/kg-1b.w.) on oral administration decreased the level of AST, ALP, ALT,
bilirubin, cholesterol, triglyceride, VLDL, MDA and increased the level of protein, HDL and antioxidants (SOD,
GSH and CAT) in rats being treated with ethanol (EtOH). Pentobarbitone -induced sleeping time study was
carried out to verify the effect on microsomal enzymes Histopathological observations confirmed the
beneficial roles of MF against EtOH-induced liver injury in rats. Possible mechanism may involve their
antioxidant activity
Effects of Metformin, Pioglitazone and Aqueous Extract of Delonix Regia on Bl...iosrjce
The effects of Delonix regia extract (d200mg, d300mg, and d400mg), metformin (m8.3mg, m12.5mg
and m16.5mg), pioglitazone (p0.5mg, p0.7mg and p0.9mg) and combined formulation of metformin and extract
(m6.25d150mg) on glycated hemoglobin status in streptozotocin-induced diabetic Albino wistar rats. Diabetic
status of these rats was assessed by estimating fasting blood glucose levels. A total of 150 albino rats were used
for the investigation and were grouped into twelve groups of twelve rats each as follows; Group I: normal
control rats (NCR). Group II: Diabetic control rats (DCR). Group III: Diabetic rats treated with d200mg.
Group IV: Diabetic rats treated with d300mg. Group V: Diabetic rats treated with d400mg. Group VI: Diabetic
rats treated with m8.3mg. Group VII: Diabetic rats treated with m12.5mg. Group VIII: Diabetic rats treated
with m16.5mg. Group IX: Diabetic rats treated with p0.5mg. Group X: Diabetic rats treated with p0.75mg.
Group XI: Diabetic rats treated with p1.0mg. Group XII: Diabetic rats treated with m125d300mg each for male
and female respectively, for a total of 56 days. After every two weeks interval of treatment for eight weeks three
rats from each group were sacrificed and blood sample were collected and analyzed for various parameters.
The result obtained showed an elevated level of glycated hemoglobin in diabetic-induced wistar albino rats
compared with normal control rats. However, there was reversal of the effects when treated with the
drug/extract. Also there was reduction in the blood glucose level of the diabetic rats treated with metformin
(from 6.37±0.69 to 5.20±0.62mmol/l), pioglitazone (from 7.30±0.21mmol/l to 4.70±0.46), aqueous extract of
Delonixregia (from 8.20±0.81mmol/l to 6.10±0.60) and combined formulation of metformin and extract (from
7.81±0.34 to 4.80±0.17), at p<0.05 confidence level when compared with diabetic control rats in the various
weeks of treatment respectively
Nurun // Le contexte comme moteur de personnalisation Grégoire Baret
Les médias numériques évoluent et refaçonnent les logiques de personnalisation: intuitives, passives, évolutive, algorithmiques, auto-adaptatives… autant de barbarismes qui sont en fait de nouvelles formes de consommation automatisée de l'information. Sont-elles véritablement adaptées aux utilisateurs? Paradoxalement, quand la personnalisation du contenu se fait en fonction du contexte, ce n'est plus forcément l'utilisateur qui choisit...
Design, création de contenus et modèles publicitaires s'en voient profondément remis en cause. On doit apprendre à jongler avec la géo-localisaiton, le multi-écrans, l'agrégation de sources disparates, ou les mécaniques issues de médias sociaux.
> Comment cerner les fondamentaux qui redessinent l'expérience media?
> Comment personnaliser au mieux en fonction du contexte?
> Quel impact sur l'expérience utilisateur?
Now-a-days, food industries are highly competitive and gaining so much of hype due to the innovation in technology and standardization of managing it.
Now-a-days, food industries are highly competitive and gaining so much of hype due to the innovation in technology and standardization of managing it. This is a capability aspect industry which is more prone to customer's approach/ need rather than operations. Servicing more to the customers with extensive ideas and material availability makes this industry more engaged to the outside world. Managing and quickly adapting with the changes makes it more innovative and excellence for the forthcoming future. Merino Services provide the business with such a solution which not only deal with the challenges but also with the requirements of those challenges and minimizes the risks thereof.
Comparison of the Hypazotemic Effects of Erythropoietin and U-74389G on Urea ...asclepiuspdfs
Aim: This study calculated the hypazotemic capacities of two drugs as follows: The erythropoietin (Epo) and the antioxidant drug U-74389G. The calculation was based on the results of two preliminary studies, each one of which estimated the hypazotemic influence, after the respective drug usage in an induced hypoxia-reoxygenation animal experiment. Materials and Methods: The two main experimental endpoints at which the blood urea levels were evaluated the 60th reoxygenation min (for the groups A, C, and E) and the 120th reoxygenation min (for the groups B, D, and F). Especially, the groups A and B were processed without drugs, groups C and D after Epo administration whereas groups E and F after U-74389G administration. Results: The first preliminary study of Epo presented a nonsignificant hypazotemic effect by 1.25% ± 1.67% (P = 0.4430). The second preliminary study of U-74389G presented a significant hypazotemic effect by 5.81% ± 1.57% (P = 0.0005). These two studies were co-evaluated since they came from the same experimental setting. The outcome of the co-evaluation was that U-74389G has 4.632148-fold more hypazotemic potency than Epo (P = 0.0000). Conclusions: The antioxidant capacities of U-74389G enhance the acute hypazotemic properties presenting 4.632148-fold more intensive hypazotemia than Epo (P = 0.0000).
Evaluation of hepatoprotective agents - Hemant KanaseHemant Kanase
1. Introduction
2. Hepatotoxicity: Mechanism
3. Therapeutic strategies available – their limitations
4. In vivo models of liver damage
- Non-invasive model
a. Chemically induced hepatotoxicity
b. Drug-induced hepatotoxicity
c. Radiation-induced hepatotoxicity
d. Metal-induced hepatotoxicity
e. Diet-induced hepatotoxicity
Models of Acute Hepatitis
Models of chronic hepatitis
Models of fibrosis
Models of cholestasis
Models of steatosis
4. Problems faced with animal studies
5. In vitro models of liver damage
6. Advantages and disadvantages of in vitro models
7. Parameters of evaluation
8. Clinical Assessment
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).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
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.
Objective: To study the effects of resveratrol in neuronal structures in traumatic brain injury (TBI).
Study Design: Thirty rats were categorized as (1) control group (n=10), saline solution administered i.p. for 14 days, (2) TBI group (n=10), trauma induced by weight-drop model on brain, and (3) TBI+Resveratrol group (n=10), 15 minutes after injury the rats were given resveratrol (10 μmoL/kg/i.p.) for 14 days. At the end of the experiment the cerebellum was excised for routine paraffin tissue protocol. Blood samples were tested for serum biochemical markers (MDA, SOD, CAT, and GSH-x).
Results: SOD, GPx, and CAT values were lowest in the TBI group. MDA and histological scores of dilations in vessels, inflammation, degeneration in neurons, apoptosis in microglia, ADAMTS8, and GFAP expressions were highest in the TBI group. Sections of the control group showed normal cerebellar histology. The trauma group showed degenerated ganglion layer, pyknotic and apoptotic Purkinje cell nuclei. Vascular thrombus was seen in the substantia alba and substantia grisea. In the Trauma+Resveratrol group, most pa- thologies observed in the TBI group were improved. In the control group, GFAP protein was expressed in granular cells, axons, dendrites, Purkinje cells, and microglia cells. In the trauma group, increased GFAP expression was observed in glial processes, neurons, and Purkinje cells. In the Trauma+Resveratrol group, GFAP was expressed in molecular layer and glial processes. In the control group, ADAMTS-4 activity was observed in granulosa layer, glial cells, and Purkinje cells. In the trauma group, ADAMTS-4 expression was positive in Purkinje cells and glial cells. In the Trauma+ Resveratrol group, ADAMTS-4 was expressed in Purkinje cells, granular cells, and glial cells.
Conclusion: GFAP and ADAMTS-4 proteins may be involved in regeneration of damaged astroglial cells and other glial cells, Purkinje cells, and synaptic extensions. We suggest that antioxidative drugs such as resveratrol may be alternative target agents in neurological disease.
Keywords: ADAMTS-4, brain, cerebellum, GFAP, rat, resveratrol, traumatic brain injury
Hepatoprotective Effect of Aqueous Extracts of Some Medicinal Plant Mixtures ...IOSRJPBS
The rhizomes of Ginger (Zingiberofficinale), Turmeric (Curcuma longa), Licorice (Glycyrrhizaglabra), the bark of Cinnamon tree,(Cinnamomumzeylanicum) and the calyces of red Roselle (Hibiscus sabdariffa L.)are herbs used in thishepatoprotective studies. This study evaluates the hepatoprotective activity of water extract mixtures using carbon tetrachloride (CCl4)-induced liver injury in rats.In vitroantioxidant activity of plant water extracts was determined using DPPH. The water extractmixtures wereadministered for 10 days; on the 10thday all rats were challenged with CCl4 except control group animals. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin levels were determined to prove the hepatoprotectiveeffect.The enzyme activities were significantly increased in CCl4 treated rats. The four water extract mixtures exhibited significant (P<0.05)><0.05) increased in all the water extract mixtures used.
Protective effects of commelina benghalensis linn (root) extract on ethanol i...IJSIT Editor
The present study was undertaken to investigate the protective effect and possible mechanism of
alcoholic (AlE) and aqueous extract (AqE) from Commelina benghalensis root (CB) on EtOH-induced hepatic
injury in Wistar rat. Hepatotoxic parameters studied in vivo include serum transaminases (AST, and ALT),
ALP, bilirubin, protein, lipid profile (Cholesterol, triglyceride, VLDL and HDL) and level of antioxidants
together with histopathological examination. Liv 52® was used as a reference hepatoprotective agent
(5ml/kg-1b.w.). AlE and AqE (200 mg/kg-1b.w.) on oral administration decreased the level of AST, ALP, ALT,
bilirubin, cholesterol, triglyceride, VLDL, MDA and increased the level of protein, HDL and antioxidants (SOD,
GSH and CAT) in rats being treated with ethanol (EtOH). Pentobarbitone -induced sleeping time study was
carried out to verify the effect on microsomal enzymes Histopathological observations confirmed the
beneficial roles of MF against EtOH-induced liver injury in rats. Possible mechanism may involve their
antioxidant activity
Effects of Metformin, Pioglitazone and Aqueous Extract of Delonix Regia on Bl...iosrjce
The effects of Delonix regia extract (d200mg, d300mg, and d400mg), metformin (m8.3mg, m12.5mg
and m16.5mg), pioglitazone (p0.5mg, p0.7mg and p0.9mg) and combined formulation of metformin and extract
(m6.25d150mg) on glycated hemoglobin status in streptozotocin-induced diabetic Albino wistar rats. Diabetic
status of these rats was assessed by estimating fasting blood glucose levels. A total of 150 albino rats were used
for the investigation and were grouped into twelve groups of twelve rats each as follows; Group I: normal
control rats (NCR). Group II: Diabetic control rats (DCR). Group III: Diabetic rats treated with d200mg.
Group IV: Diabetic rats treated with d300mg. Group V: Diabetic rats treated with d400mg. Group VI: Diabetic
rats treated with m8.3mg. Group VII: Diabetic rats treated with m12.5mg. Group VIII: Diabetic rats treated
with m16.5mg. Group IX: Diabetic rats treated with p0.5mg. Group X: Diabetic rats treated with p0.75mg.
Group XI: Diabetic rats treated with p1.0mg. Group XII: Diabetic rats treated with m125d300mg each for male
and female respectively, for a total of 56 days. After every two weeks interval of treatment for eight weeks three
rats from each group were sacrificed and blood sample were collected and analyzed for various parameters.
The result obtained showed an elevated level of glycated hemoglobin in diabetic-induced wistar albino rats
compared with normal control rats. However, there was reversal of the effects when treated with the
drug/extract. Also there was reduction in the blood glucose level of the diabetic rats treated with metformin
(from 6.37±0.69 to 5.20±0.62mmol/l), pioglitazone (from 7.30±0.21mmol/l to 4.70±0.46), aqueous extract of
Delonixregia (from 8.20±0.81mmol/l to 6.10±0.60) and combined formulation of metformin and extract (from
7.81±0.34 to 4.80±0.17), at p<0.05 confidence level when compared with diabetic control rats in the various
weeks of treatment respectively
Nurun // Le contexte comme moteur de personnalisation Grégoire Baret
Les médias numériques évoluent et refaçonnent les logiques de personnalisation: intuitives, passives, évolutive, algorithmiques, auto-adaptatives… autant de barbarismes qui sont en fait de nouvelles formes de consommation automatisée de l'information. Sont-elles véritablement adaptées aux utilisateurs? Paradoxalement, quand la personnalisation du contenu se fait en fonction du contexte, ce n'est plus forcément l'utilisateur qui choisit...
Design, création de contenus et modèles publicitaires s'en voient profondément remis en cause. On doit apprendre à jongler avec la géo-localisaiton, le multi-écrans, l'agrégation de sources disparates, ou les mécaniques issues de médias sociaux.
> Comment cerner les fondamentaux qui redessinent l'expérience media?
> Comment personnaliser au mieux en fonction du contexte?
> Quel impact sur l'expérience utilisateur?
Now-a-days, food industries are highly competitive and gaining so much of hype due to the innovation in technology and standardization of managing it.
Now-a-days, food industries are highly competitive and gaining so much of hype due to the innovation in technology and standardization of managing it. This is a capability aspect industry which is more prone to customer's approach/ need rather than operations. Servicing more to the customers with extensive ideas and material availability makes this industry more engaged to the outside world. Managing and quickly adapting with the changes makes it more innovative and excellence for the forthcoming future. Merino Services provide the business with such a solution which not only deal with the challenges but also with the requirements of those challenges and minimizes the risks thereof.
In a fast pace environment, where the technology changes in micro seconds, desire a change which needs to be forecast in the market. The equipment in these industries needs to be advanced and the changing of time plays a significant role in equipment life cycle.The solution needs to be specified enough that it can control the business as a whole. Planning and scheduling are the most efficient paths in industrial equipment and machinery vertical. Meeting up the solution and controlling the performance packed in one industry, Merino Services fulfill all the projects and operations that begin with different processes and ends up with another process.
Harris Interactive a constitué, avec France Télévisions, un panel de citoyens : 2017idées. Les citoyens sont invités à parler de politique, de l’actualité, des enjeux de la campagne… Harris Interactive s’appuie sur ce panel pour réaliser des enquêtes et des sondages pré-électoraux (relatifs à la l’élection présidentielle) dans le cadre de l’Emission Politique présentée par David Pujadas, Léa Salamé et Karim Rissouli, et diffusée sur France 2. Cette semaine, Harris Interactive a interrogé les Français sur leurs intentions de vote à la Présidentielle ainsi que sur les candidats de cette élection.
Dado la importancia de la relación que debe haber entre el padre y el hijo este estudio se refiere a la falta que hace un padre en la crianza de un niño, para que pueda tener un adecuado desarrollo psicosocial y físico. Por consiguiente, las figuras paternas, aquellas personas que fingen el rol de mamá y papá, se encargarán de lograr que el hijo, adquiera perspectivas propias y personales. Son la base que dará fuerza a superar cualquier obstáculo a través de la guía, el cuidado, el afecto y los límites que los niños necesitan.
À l’occasion de « l’Émission Politique » diffusée en direct jeudi 9 mars 2017 sur France 2, Harris Interactive a mis en place un dispositif permettant aux Français d’apprécier en temps réel la prestation de l’invité, Benoît Hamon, candidat à l’élection Présidentielle. Un échantillon représentatif de Français, invité à regarder «L’Émission Politique» a ainsi répondu à des questions sur cet invité. - http://harris-interactive.fr/opinion_polls/sondage-pour-lemission-politique-invite-benoit-hamon/
Conscience, anticipation, action : quelle posture des dirigeants d’entreprise face au vieillissement démographique ? -
Au 1er janvier 2050, si les tendances démographiques récentes se maintiennent, la France métropolitaine compterait, selon l’Insee, 70 millions d’habitants, soit 9,3 millions de plus qu’en 2005. En 2050, un habitant sur trois serait âgé de 60 ans ou plus, contre un sur cinq en 2005. Ainsi, la part des jeunes diminuerait, ainsi que celle de la population active. Ces évolutions démographiques vont nécessairement s’accompagner d’un changement des besoins des Français, de leurs attentes, de leur mode de vie et de consommation, voire d’une émergence d’une « silver économie ».
Face à ce constat, Malakoff Médéric a sollicité Harris Interactive pour réaliser une enquête auprès de dirigeants d’entreprises de 50 salariés et plus, afin de dresser un état des lieux de la perception par les entreprises de l’enjeu du vieillissement démographique, et de la façon dont elles s’y préparent. Plus précisément : les entreprises françaises ont-elles conscience de l’enjeu du vieillissement de la population ? Dans quelle mesure l’anticipent-elles ? Et quelles actions mettent-elles en œuvre pour y faire face ?
Baromètre Harris Interactive – 1ère vague
Harris Interactive présente les résultats de son étude sur les nouveaux moyens de paiements : quels concepts sont amenés à se démocratiser, à disparaitre ?
Cette étude permet d’établir un panorama des usages actuels du grand public en matière de moyens de paiement et surtout de mesurer son appétence pour 10 nouveautés : la carte bancaire sans contact, la carte titre restaurant, le paiement par sms, le paiement par QR Code, la carte bancaire sans contact, le paiement à distance via smartphone, les services de paiement en ligne, la carte prépayée rechargeable, les monnaies virtuelles et les monnaies locales.
http://harris-interactive.fr/?p=9080
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.
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.
Objective: To investigate the effect of sildenafil on reducing the impact of hepatic ischemia/reperfusion (HIR) injury established by Pringle maneuver on the heart of rats.
Study Design: Forty Wistar albino rats were divided into 4 groups: Sham (laparotomy only), Control (laparotomy following sildenafil application), IR (ischemia/reperfusion injured by HIR), and IR+SIL (injured by HIR following sildenafil application). Ischemia was developed by clamping the hepatoduodenal ligament for 30 minutes; then reperfusion was applied for 30 minutes. Sildenafil (single dose of 50 mg/kg) was administered by oral gavage for 15 minutes before ischemia. Blood samples of rats were collected from Sham and Control groups at 60 minutes and from IR and IR+SIL groups at 30 minutes after initiation of reperfusion for biochemical analysis. Meanwhile, heart tissues were sampled for biochemical analysis. Malondialdehyde (MDA) and total antioxidant capacity (TAC) in serum samples and TAC, total oxidative capacity (TOC), and oxidative stress index in heart tissues were examined biochemically.
Results: Serum MDA levels were elevated significantly in the IR and IR+SIL groups as compared to the sham group. Sildenafil treatment inhibited MDA increase considerably in the IR+SIL group as compared to the IR group. Serum TAC levels were elevated significantly in the sildenafil and control groups (compared with sham groups) and in the IR+SIL group (compared with the IR group). TAC levels detected in heart tissue increased significantly in the IR group as compared to the sham group; however, sildenafil treatment had no effect on this increase.
Conclusion: Heart tissue was affected by HIR. It was revealed that sildenafil treatment may prevent the oxidative stress via increasing serum TAC levels in both control and IR+SIL groups.
Background: Body of literature are becoming pronounced that pathological condition in one organ of the body might have an effect on other distal organs owing to the fact, that the entire body metabolism is orchestrated centrally.
Pathological events occurring in an organ are likely to be extended to other organs. Pretreatment that minimize these events are presumed to be beneficial to the extended organs.
Methods: Following 30 min of ischemia and 48 h of reperfusion in the kidney, rats under anesthesia were sacrificed and blood sample collected through cardiac puncture. Serum level of troponin I, and activities of total creatine kinase (CK), mass creatine kinase (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma –glutamyl transferase (GGT) were estimated spectrophotometrically.
Results: Serum troponin I increased to 0.031 ± 0.001 ng/ml in the ischemic group, and following pretreatment with Lmm (600mg/kg), serum level of troponin I decreased significantly to 0.021 ± 0.001 ng/ml (P<.05).><.05),><.05)><.05).
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
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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Ameliorating Effect of Frankincense on Red Blood Cells of Alloxan Induced-Dia...inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, 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.
Genotoxicity of Goji Berry (Lyciumbarbarum) In Vivo Mammalian Cellsinventionjournals
Lyciumbarbarum (Gojji berry) belongs to family Salonaceae which is found in China and Himalayan. This herb is used to prevent various diseases and in medical treatments as an alternative medicine being widely used for its antioxidant and revitalizing potential effects. In recent years, Gojji has become increasingly popular in Europe and North America as a "superfruit" and dietary supplement. The belief that herbal products do not bring any risk to health, is part of popular culture. However the term "natural" assigned to many products cannot assure no health risk. The aim of this study was to evaluate the possible genotoxic effects of aqueous extract of Lyciumbarbarum (Gojji berry) by micronucleus test and comet assay. Thirty Rattus norvegicus were divided into three equal groups: 1) experimental group, submitted to Gojji berry (200mg/kg orally); 2) positive control group (cyclophosphamide), and; 3) negative control group (distilled water). Micronucleus Tests were done by smear method of bone marrow cells performed after 48h for acute, and 72h for chronic exposure. The comet assay was performed on peripheral blood taken from the tail of each animal 4h, and 24h after intervention. Cytotoxicity was assessed by observing the DNA damage measuring the percentage of DNA in the tail (% DNA- measurement of the proportion of the total DNA present in the tail) and the tail moment (TM-tail length times the percentage of DNA in the tail), calculated by 100 nucleoids per animal and the presence of micronuclei in 2,000 polychromatic erythrocytes per animal. Analysis of variance (ANOVA) followed by Tukey test at 5% significance was used comparing the results. The data showed no significant difference in the frequency of DNA damage and the number of micronuclei between the experimental group and the negative control group. The results also suggest that the aqueous extract of Lyciumbarbarum (Gojji berry) at the dose of 200 mg/kg showed no genotoxic effect, which could, to a certain point, justifies its use.
Genotoxicity of Goji Berry (Lyciumbarbarum) In Vivo Mammalian Cellsinventionjournals
Lyciumbarbarum (Gojji berry) belongs to family Salonaceae which is found in China and Himalayan. This herb is used to prevent various diseases and in medical treatments as an alternative medicine being widely used for its antioxidant and revitalizing potential effects. In recent years, Gojji has become increasingly popular in Europe and North America as a "superfruit" and dietary supplement. The belief that herbal products do not bring any risk to health, is part of popular culture. However the term "natural" assigned to many products cannot assure no health risk. The aim of this study was to evaluate the possible genotoxic effects of aqueous extract of Lyciumbarbarum (Gojji berry) by micronucleus test and comet assay. Thirty Rattus norvegicus were divided into three equal groups: 1) experimental group, submitted to Gojji berry (200mg/kg orally); 2) positive control group (cyclophosphamide), and; 3) negative control group (distilled water). Micronucleus Tests were done by smear method of bone marrow cells performed after 48h for acute, and 72h for chronic exposure. The comet assay was performed on peripheral blood taken from the tail of each animal 4h, and 24h after intervention. Cytotoxicity was assessed by observing the DNA damage measuring the percentage of DNA in the tail (% DNA- measurement of the proportion of the total DNA present in the tail) and the tail moment (TM-tail length times the percentage of DNA in the tail), calculated by 100 nucleoids per animal and the presence of micronuclei in 2,000 polychromatic erythrocytes per animal. Analysis of variance (ANOVA) followed by Tukey test at 5% significance was used comparing the results. The data showed no significant difference in the frequency of DNA damage and the number of micronuclei between the experimental group and the negative control group. The results also suggest that the aqueous extract of Lyciumbarbarum (Gojji berry) at the dose of 200 mg/kg showed no genotoxic effect, which could, to a certain point, justifies its use.
Genotoxicity of Goji Berry (Lyciumbarbarum) In Vivo Mammalian Cellsinventionjournals
Lyciumbarbarum (Gojji berry) belongs to family Salonaceae which is found in China and Himalayan. This herb is used to prevent various diseases and in medical treatments as an alternative medicine being widely used for its antioxidant and revitalizing potential effects. In recent years, Gojji has become increasingly popular in Europe and North America as a "superfruit" and dietary supplement. The belief that herbal products do not bring any risk to health, is part of popular culture. However the term "natural" assigned to many products cannot assure no health risk. The aim of this study was to evaluate the possible genotoxic effects of aqueous extract of Lyciumbarbarum (Gojji berry) by micronucleus test and comet assay. Thirty Rattus norvegicus were divided into three equal groups: 1) experimental group, submitted to Gojji berry (200mg/kg orally); 2) positive control group (cyclophosphamide), and; 3) negative control group (distilled water). Micronucleus Tests were done by smear method of bone marrow cells performed after 48h for acute, and 72h for chronic exposure. The comet assay was performed on peripheral blood taken from the tail of each animal 4h, and 24h after intervention. Cytotoxicity was assessed by observing the DNA damage measuring the percentage of DNA in the tail (% DNA- measurement of the proportion of the total DNA present in the tail) and the tail moment (TM-tail length times the percentage of DNA in the tail), calculated by 100 nucleoids per animal and the presence of micronuclei in 2,000 polychromatic erythrocytes per animal. Analysis of variance (ANOVA) followed by Tukey test at 5% significance was used comparing the results. The data showed no significant difference in the frequency of DNA damage and the number of micronuclei between the experimental group and the negative control group. The results also suggest that the aqueous extract of Lyciumbarbarum (Gojji berry) at the dose of 200 mg/kg showed no genotoxic effect, which could, to a certain point, justifies its use.
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.
Objective: Ischemia-reperfusion (I/R) leads to reactive oxygen species formation and cell death in kidney tissue with injury and organ transplantation. Simvastatin (SIM) is an antioxidant, anti-inflammatory, and anticoagulant agent. Alterations in I/R-induced acute kidney injury model with SIM treatment were analyzed.
Study Design: Wistar rats (n=28) were grouped into Sham, Ischemia, I/R, and I/R+SIM treated. Left rat kidney renal vessels were clamped for 60 minutes for ischemia, and the I/R group had 6 hours of reperfusion. 10 mg/kg SIM was given orally for 28 days. MDA, GSH, and MPO were analyzed. Kidney tissues were paraffin embedded, and primary antibodies TNF-α and caspase-3 were applied for immunohistochemistry.
Results: In the I/R group, intense inflammatory cell infiltration around the vessels and necrosis in the glomerular structures were observed. In the treated group, proximal and distal tubular cells were found to be close to normal. Immunoexpression of caspase-3 in the ischemia group was positive in degenerative glomeruli. In the treated group, TNF-α expression was negative in the glomerular structures. MDA and MPO levels were significantly increased in ischemia and I/R.
Conclusion: We suggest that SIM treatment improved kidney tissue structure and function in a model of I/R injury.
Keywords: caspase-3; immunohistochemistry; ischemia/reperfusion; kidney; MPO; simvastatin
2. 2 Integrative Cancer Therapies
Materials and Methods
Animals
A total of 48 male, 10-week-old Sprague-Dawley rats
(Harlan, Indianapolis, IN) were housed in the University of
Northern Colorado Animal Research Facility in 12-hour
light/dark conditions at thermoneutrality (21.0°C ± 1.0°C)
and fed rodent lab chow (Harlan Teklad 2016) and distilled
water ad libitum. The animal use protocol was approved by
the University of Northern Colorado Animal Care and Use
Committee and is in accordance with the Animal Welfare
Act. Initially, rats were randomly assigned to treadmill
exercise (TM, n = 23) or sedentary (SED, n = 25) conditions
for 10 weeks. Following the activity period, rats were ran-
domly assigned to receive either DOX or saline injections.
Experimental Design
Rats assigned to TM trained for 10 weeks using a progres-
sive training protocol on a motorized treadmill (Table 1).
An initial acclimation to the treadmill was performed at
week 0. Exercise duration and intensity (initial setting: 25
m/min, 0% slope, 20 min/session, 5 d/wk) gradually
increased until week 8, when it reached final conditions (30
m/min, 18% slope, 60 min/session, 5 d/wk).Acontrol group
(SED+SAL/10/12.5) remained sedentary (normal cage
activity) for 10 weeks. TM received bolus DOX (Sagent:
Schaumburg, IL) or saline injections 24 hours after the last
training session. Injections were administered intraperito-
neally according to milligram per kilogram body weight.
TM+10 and SED+10 animals received 10 mg/kg of DOX.
TM+12.5 and SED+12.5 animals received 12.5 mg/kg of
DOX. TM+SAL and SED+SAL animals received equiva-
lent volumes of saline. Animals were anesthetized with
heparinized sodium pentobarbital 72 hours after injections.
After a tail-pinch reflex was absent, animals were killed
humanely by aortic exsanguination, and the thymus was
excised.
Tissue Preparation
Rat thymus glands were isolated and maintained in ice-cold
phosphate buffered solution (PBS 1×) supplemented with
glucose. After cleansing and wet weight recording, the thy-
mus was briefly exposed (<10 s) to hypotonic PBS (10×) to
lyse any remaining red blood cells on the tissue and quickly
restored to 1× PBS. Lymphocytes were expressed from the
thymus by gently teasing organs between frosted-edge glass
slides into a cell culture dish containing 5 mL PBS. Slides
were rinsed with PBS over the collecting dish to ensure a
complete thymocyte delivery. After gentle mixing, 10 µL of
thymocytes in PBS were added to a polypropylene tube
with an equal volume of trypan blue (Sigma-Aldrich, St
Louis, MO). The blend of thymocyte solution/trypan blue
was thoroughly mixed via pipette and centrifuged before
being added to a hemocytometer slide for manual viable
cell count. An upright 10× microscope and CellSens soft-
ware (Olympus, Tokyo, Japan) were used to examine the
hemocytometer slide. Exclusion of trypan blue indicated
viable status, whereas inclusion staining denoted perfora-
tion of cell membranes in nonviable thymocytes.
Immediately after T-cell collection, thymus tissue was flash
frozen in liquid nitrogen and stored at −80°C until biochem-
ical analysis.
Lipid Peroxide Determination
Lipid peroxidation was assessed in thymic tissue as an indi-
cator of DOX-induced cellular oxidative damage.
Malondialdehyde and 4-hydroxyalkenals (MDA+4-HAE)
were determined using a commercially available kit (Oxis
International, Inc, Portland, OR). Thymic tissues were
homogenized in RIPA buffer and centrifuged at 3000g for
10 minutes. Supernatant was removed, and protein concen-
tration was analyzed using the Bradford protocol.16
Total
protein concentrations were standardized, and a 200-µL ali-
quot of each sample was added to 650 µL of N-methyl-2-
phenylinodole and briefly vortexed. Next, 150 µL of
methanesulfonic acid was added, vortexed, and incubated
(45°C) for 60 minutes. Following centrifugation at 15,000g
for 10 minutes, supernatant was transferred to a cuvette, and
absorbency was measured at 586 nm. A standard curve of
provided reagents and different concentrations of MDA
provided a linear regression analysis for MDA+4-HAE at r²
= 0.99990. All samples were run in duplicate, and if absor-
bency differed by >5%, samples were reassayed.
Statistical Analysis
All data are presented as mean ± standard error of the mean.
A 2-factor (Activity × Drug) ANOVA was performed to
determine differences in physical characteristics (body and
tissue masses), viable T-cell numbers, and MDA+4HAE
concentrations. When a significant difference was detected
between groups, a Bonferroni post hoc analysis determined
which groups differed. Significance was set at a P < .05
level. Statistical analyses were performed using the Prism
software package (GraphPad, LaJolla, CA).
Results
Animal Characteristics
All TM rats completed exercise training. Animal character-
istics are presented in Table 2. Body mass (BM) from the
SED+12.5 group was significantly less than that in SAL
groups. Rats receiving DOX displayed significant reduction
in BM, except TM+12.5. This group did not significantly
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3. Quinn et al 3
differ from the TM+SAL group. All rats receiving DOX
possessed significantly lower thymus masses than SAL ani-
mals, as seen in Figure 1. Thymus mass relative to BM was
also significantly lower in rats receiving DOX.
Thymocyte Viability
Figure 2 illustrates viable T-cell numbers between groups.
There was a significant drug effect observed (P = .0107) with
DOX administration decreasingT-cell numbers. No significant
exercise effect or interaction was observed, and post hoc test-
ing did not reveal any between-group differences (P > .05).
Lipid Peroxidation
As shown in Figure 3, a significant drug effect was observed
in MDA+4HAE levels (P < .0001), indicating that DOX
treatment elevated oxidative stress levels. A significant
activity effect (P < .0001) was seen, with chronic exercise
suppressing levels of lipid peroxidation. Additionally, a sig-
nificant interaction (P = .0385) was observed. TM+10
exhibited significantly less MDA+4HAE than SED+10 and
was not significantly different from SED+SAL. TM+12.5
thymus had significantly less MDA+4HAE than the
SED+12.5 as well.
Discussion
To our knowledge, this is the first study to examine the
effects of chronic exercise prior to DOX treatment on the
thymus. We examined changes in tissue mass, local T-cell
count, and MDA+HAE. Our main finding was that chronic
endurance exercise significantly reduced levels of oxidative
stress following DOX injections. This finding is in agree-
ment with previous studies suggesting that chronic exercise
elevates antioxidant enzyme levels and activity. However,
exercise did not prevent thymic involution and thymocyte
loss. Although T-cell number was not significantly different
between TM and SED animals receiving 10 mg/kg
(P = .1701), a trend of higher viable T-cell count with endur-
ance exercise was noted.
DOX is an antineoplastic agent used in a wide variety of
cancers. In spite of its efficacy combating cancerous cells,
accompanying side effects limit dosing. The most recog-
nized side effect accompanying DOX administration is car-
diotoxicity because DOX accumulates in cardiac cells and
undergoes redox cycling resulting in the formation of
ROS.5,17
ROS-associated damage occurs as peroxidizing of
Table 2. Physical Characteristics of Subjects.a
SED+SAL
(n = 8)
SED+10 mg/kg
(n = 8)
SED+12.5mg/kg
(n = 7)
TM+SAL
(n = 9)
TM+10 mg/kg
(n = 9)
TM+12.5 mg/kg
(n = 7)
Body mass (g) 432.8 ± 6.3 401.0 ± 10.8 375.9 ± 7.6b,c
441.9 ± 9.2 394.9 ± 16.3 422.6 ± 16.1
Δ Body mass (g) 2.8 ± 4.9 −38.7 ± 3.8b,c
−32.1 ± 8.5b,c
0.8 ± 2.9 −44.0 ± 6.4b,c
−26.9 ± 7.1b
Thymus mass (g) 265.7 ± 13.6 123.0 ± 10.3b,c
122.8 ± 15.7b,c
258.8 ± 17.6 113.1 ± 13.6b,c
116.4 ± 9.9b,c
Thymus/Body (mg/kg) 614.8 ± 35.3 282.7 ± 43.4b,c
319.1 ± 136.4b,c
556.5 ± 46.4 288.8 ± 29.9b,c
275.0 ± 20.3b,c
Abbreviations: SED, sedentary; SAL, saline treated; TM, treadmill trained; 10 mg/kg, 10 mg/kg doxorubicin treated; 12.5 mg/kg, 12.5 mg/kg doxorubicin
treated; Δ Body mass, change in body mass before and after injections.
a
Data are mean ± standard error of the mean.
b
Significantly different compared with sedentary/saline group (P < .05).
c
Significantly different compared with exercise/saline group (P < .05).
Figure 1. Thymus size comparison: A. SED+DOX; B. SED+SAL.
Abbreviations: SED, sedentary; DOX, doxorubicin; SAL, saline treated.
Table 1. Progressive Treadmill Training Protocol.
Week
1 2 3 4 5 6 7 8 9 10
Speed (m/min) 25 25 25 30 30 30 30 30 30 30
Incline (%) 0 0 0 3 6 9 12 15 18 18
Duration (minutes) 20 30 30 60 60 60 60 60 60 60
by guest on June 2, 2016ict.sagepub.comDownloaded from
4. 4 Integrative Cancer Therapies
the lipid constituting membranes, at the cellular, mitochon-
drial, and nuclear levels.18
Additionally, DOX intercalates
DNA and stabilizes topoisomerases, preventing synthesis
and replication. DOX-affected cells may undergo apoptotic
events with eventual cell death. Although cardiac tissue has
received a majority of the attention regarding associated
toxicity, DOX has also been shown to induce thymic invo-
lution and T-cell senescence.1
Additionally, isolated rat thy-
mocytes exposed to DOX undergo DNA fragmentation,
with subsequent increases in ROS scavenging enzyme
activities of superoxide dismutase (SOD) and catalase
activities.4
Although elevated antioxidant enzymes could
not prevent apoptosis, the stimulation of antioxidant
enzymes suggests that apoptosis may be partly a result of
free radical formations. In vitro exposure of murine lym-
phocytes to DOX induces rapid DNA degradation in mostly
noncycling cells, with greater cell death dependent on DOX
concentrations.19
The immune system functions to identify and eliminate
foreign antigens that enter the body.20
Leukocytes, or white
blood cells, originate in bone marrow, but mature in organs,
including the thymus, spleen, lymph nodes, and peripheral
lymphoid organs. Leukocytes that act directly on antigens
are B- and T-cells, with B-cells creating antibodies specific
to antigens and T-cells destroying targeted cells. B-cells
mature in bone marrow, whereas T-cells mature in the thy-
mus. T-cells, or thymocytes, are cytotoxic (CD8+
), helper
(response-enhancing, CD4+
), or regulatory (Treg) cells.
Various conditions of stress have been shown to decrease
T-cell number and lead to thymic involution, including anx-
iety, physical stress, and heat/cold exposure.21-24
Physical stress, such as exercise, may alter immunologi-
cal capacity. Nieman’s25
J-shaped model of exercise and
immunity suggests that exercise can enhance or reduce
immune function depending on frequency, duration, and
intensity of exercise performed. Evidence suggests that
strenuous acute bouts of exercise decrease circulating lym-
phocyte number while increasing apoptosis, as evidenced
by DNA fragmentation.26,27
Conversely, submaximal exer-
cise in mice demonstrates fewer apoptotic and higher num-
bers of viable T-cells compared with sedentary controls.28
Although peroxidation of lipids of cellular and mitochon-
drial membranes have been primarily implicated in the
induction of apoptosis, isolated rat nuclei exposed to DOX
also exhibit membrane peroxidation.29
In addition to ele-
vated ROS following strenuous exercise, increased gluco-
corticoids, intracellular Ca2+
, and inflammatory signals may
induce apoptosis during times of suppressed immune func-
tion.30
A rise in glucocorticoid release and intracellular Ca2+
levels may further induce apoptosis in lymphocytes.31
Glucocorticoids released in response to exercise, such as
cortisol, have been shown to induce pyknosis and DNA
fragmentation in isolated thymocytes.32
In accordance with the J-shaped model, studies examin-
ing response to chronic and acute endurance exercise have
revealed opposing lymphocytic effects. Chronic exercise
improved thymic structural quality and circulating lympho-
cyte populations, whereas acute, exhaustive bouts had
Figure 2. Graphical representation of viable T-cell number:
data are mean ± standard error of the mean. Significant drug
effect (P = .0107); no activity or interaction effect (P > .05).
Abbreviations: SED, sedentary; TM, treadmill trained; SAL, saline
treated; 10 mg/kg, 10 mg/kg doxorubicin treated; 12.5 mg/kg, 12.5 mg/kg
doxorubicin treated.
Figure 3. Graphical representation of lipid peroxidation in the
thymus: data are mean ± standard error of the mean.
Abbreviations: SED, sedentary; TM, treadmill trained; SAL, saline
treated; 10 mg/kg, 10 mg/kg doxorubicin treated; 12.5 mg/kg, 12.5 mg/kg
doxorubicin treated; DOX, doxorubicin.
a
Significantly different as compared with sedentary/saline group (P < .05).
b
Significantly different as compared with exercise/saline group (P < .05).
c
Significantly different as compared with sedentary/DOX 10-mg/kg group
(P < .001).
d
Significantly different as compared with sedentary/DOX 12.5-mg/kg
group (P < .01).
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5. Quinn et al 5
negative effects on the thymus, lymphocyte populations,
and other immune organs.33
Specifically, thymic tissues
express significantly elevated membrane lipid peroxidation
after mice were acutely run to exhaustion.27
Furthermore,
T-cells exhibited higher levels of intracellular Ca2+
and lipid
peroxidation after exercise.34
Navalta et al35
demonstrated
that exercise intensity affects circulating lymphocyte apop-
tosis, with significance occurring above 60% of VO2max in
untrained human subjects performing incremental treadmill
tests to exhaustion.
To determine training effects on lymphocyte apoptosis in
response to chronic training, Mooren et al36
compared
trained runners against poorly trained individuals and found
cell death induced by exercise in the poorly trained indi-
viduals. Enhanced serum antioxidant enzyme production
with chronic wheel running (10 months) in mice demon-
strated reduced ROS-induced apoptosis in immune cells.37
An increase in antioxidant enzymes through chronic exer-
cise training may attenuate ROS-induced damage seen in
lymphocytes.7
Additionally, 8 weeks of treadmill- and
swim-training induced significantly higher levels of CD4+
and CD8+
T-cells in the thymus of Sprague-Dawley rats.38
Although acute, exhaustive exercise may elevate glucocor-
ticoids, which initiate lymphocytic cell death, chronic sub-
maximal training may not trigger such levels.
It has been long known that exhaustive exercise in rats
induces significant thymic atrophy.21
Additionally, studies
demonstrate that lymphocyte apoptosis occurs immediately
following high-intensity exercise.26
Using a submaximal,
chronic training program, however, may enhance antioxi-
dant enzyme concentrations and alleviate ROS-related lym-
phocyte apoptosis without the negative side effects seen
with exhaustive bouts. Sugiura et al39
determined that 12
weeks of forced, submaximal running in mice (15 m/min)
significantly increased spleen and liver mass while slightly
enlarging thymic tissue compared with sedentary animals.
Using a swim-training model for 8 weeks, Pereira et al7
demonstrated that lipid peroxidation levels were signifi-
cantly decreased in thymus tissues versus sedentary con-
trols. Additionally, citrate synthase and GPX levels were
significantly elevated. Short-term exercise (3 weeks) in
hemodialysis patients does not restore T-cell numbers com-
parable to normal healthy individuals, but T-cell activity is
elevated when compared with sedentary hemodialysis
patients.40
It is suggested that chronic, moderate exercise
may increase total T-cell number with amplified activity.41
This study did not examine the effects of exercise intensity
with DOX treatment on thymic changes.
The thymus naturally reduces the size and total number
of T-cells in an age-dependent fashion, leading to decreased
immune resistance, referred to as immunosenescence.1,42
As
humans age, the number of cytotoxic CD8+
T-cells tend to
decrease with senescence. Moderate exercising older adults
exhibit greater proportions of CD8+
T-cells when compared
with sedentary individuals.43
Patients receiving chemother-
apy also have a suppressed immune system. As demon-
strated in this study, acute DOX treatment significantly
reduces size of thymic tissue and reduces viable T-cell num-
bers. There was an exercise effect, with endurance-trained
animals presenting significantly less thymic lipid peroxida-
tion when compared with sedentary paired groups.
Furthermore, the level of MDA+4HAE in endurance-
trained rats receiving 10 mg/kg DOX (TM+10) was not sig-
nificantly different from that in sedentary/saline animals
(SED+SAL). A significant drug effect was noted with DOX
treatment in total T-cell number, and prior exercise did not
significantly attenuate these losses. The addition of DOX-
induced thymus dysfunction may further compromise the
ability of patients to stave off further infections experienced
during treatment and shortly thereafter. A prior endurance
exercise program may reduce the thymic-related losses in
size and T-cell number.
Clinical implications of this study suggest that chroni-
cally trained individuals may demonstrate greater
immune response following chemotherapy treatment
than sedentary counterparts. Clearly, this study demon-
strates that DOX treatment results in significant thymic
atrophy. Production of naïve T-cells is governed by thy-
mus output and not replication of the circulating cell
pool.44
Thymic involution, or atrophy, results in decreased
T-cell development and thymopoiesis.45
Conversely,
increased size of thymus may complement T-cell produc-
tion and new antigen resistance in the time following
treatment. DeNardo et al46
suggest that, in addition to
increased macrophage number, an abundance of T-cells
indicate greater survival rate among breast cancer
patients. Additionally, Feng et al47
showed that mice in
an oxidative stress model exhibit significantly less T-cell
proliferation than controls. Exercise preconditioning
lowered markers of oxidative stress and may attenuate
decreased T-cell production following DOX treatment.
The optimal cumulative dose of DOX for induction of
congestive heart failure (CHF) has been established at
12.45 mg/kg in rats.48
The doses used (10 and 12.5
mg/kg) in this study may elicit outcomes similar to those
experienced in clinical settings. However, clinical admin-
istration of DOX is typically delivered in small doses
over the course of treatment. The single bolus injection
strategy is a limitation of the present study. Viable T-cell
numbers in this study may have been overestimated in
samples because of cells undergoing early stages of
apoptosis. During early apoptosis, cell membranes
remain intact and do not allow trypan blue entry into
cells. The early-apoptotic T-cells were not distinguished
in this study. Although this study did not examine circu-
lating thymocytes, animals had not exercised for 3 days
after injection, and lymphocyte circulation typically ele-
vates following stressful conditions.
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6. 6 Integrative Cancer Therapies
Conclusion
Data from the current study suggest significant decreases in
thymic lipid peroxidation with chronic endurance exercise
prior to DOX administration. Additionally, exercise precon-
ditioning may have contributed to an increasing trend in
T-cell count. Individuals who aerobically exercise at sub-
maximal intensities prior to chemotherapy may offset thy-
mocytic depressions typical with DOX treatment. The
observed depression in levels of MDA+4HAE may be
attributed to elevated antioxidant enzyme levels and activ-
ity associated with chronic endurance exercise training.
Acknowledgments
The authors wish to thank Gregory DeKrey for his technical con-
tribution to this investigation.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
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