The document discusses a study on the effects of the phosphodiesterase type-5 (PDE5) inhibitor tadalafil on liver ischemia/reperfusion injury in rats. The study found that tadalafil treatment before ischemia/reperfusion injury helped restore normal liver enzyme levels, reduced oxidative stress and inflammation in liver tissue, and decreased levels of tumor necrosis factor-alpha, interleukin-6, and intercellular adhesion molecule-1. Histological analysis also showed tadalafil treatment helped protect against liver damage. The findings suggest that modulating the inflammatory response may be one mechanism by which tadalafil provides hepatoprotection against ischemia/reperfusion injury.
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.
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
Objective: A spinal cord injury (SCI) is damage to the spinal cord either from trauma, loss of its normal blood supply, or compression from tumor or infection. In this study we focused on alterations in the bladder tissue with angiogenic and apoptotic aspects after spinal cord injury.
Study Design: Twenty Wistar Albino rats were categorized as control and SCI groups. At T7-T9 vertebras, a steel rod was dropped from 10 cm to create a spinal cord injury under anesthesia. Rats were decapitated and spinal tissue was processed to measure malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO).
Results: MDA, MPO, epithelial degeneration, vascular dilation, inflammation, VEGF, and APAF-1 expressions in the SCI group were statistically higher than those in the control group. GSH content of the SCI group was statistically lower than that in the control group. In the hematoxylin-eosin–stained sections of the control group, normal histology was observed in bladder tissue. In the SCI group, degeneration epithelial cells, thinned epithelium, increased fibrosis, dilated and congested blood vessels, and hyperplastic endothelial cells were observed. In the control group, VEGF expression was slightly observed in some epithelial cells and vascular cells. In the SCI group, VEGF expression was increased in inflammatory and vascular endothelial cells. For APAF-1 expression, the control group showed no expression. In the SCI group, APAF-1 expression was positive in degenerated epithelial cells and connective tissue cells.
Conclusion: It is thought that the urination reflex was affected due to increased inflammation in the bladder tissue, leading to alterations in the regulation and function of the muscles.
Objective: To investigate the immunohistochemical staining of hypoxia-inducible factor 1-alpha (HIF-1α) and Ki-67 expression in the placenta of pregnant women with placenta previa and placenta accreta.
Study Design: Thirty placentas (10 normotensive, 10 placenta previa, and 10 placenta accreta) were processed for routine histological tissue processing. The biochemical parameters of patients were recorded. Placentas were stained with hematoxylin-eosin and HIF-1α and Ki-67 immunostaining.
Results: Normal histology was observed in placentas of normotensive pregnant women. Placenta previa sections showed increased syncytial knots, intervillous hemorrhage, fibrin accumulation, and hyalinization. In placenta accreta sections, increased syncytial nodes, vascular dilation/congestion, fibrin accumulation, and hyalinization were observed. Normotensive placentas showed no HIF-1α expression. In placenta previa tissues, high HIF-1α expression was observed in vascular endothelial cells, villous stromal cells, and syncytial knots. High HIF-1α expression was recorded in villous stromal cells and cytotrophoblast cells in placenta accreta. In normotensive placental tissues, no Ki-67 expression was observed. In placenta previa sections, high Ki-67 expression was observed mostly in root villi stromal cells and some endothelial cells. High Ki-67 expression was observed mostly in villi stromal cells of placenta accreta.
Conclusion: It is thought that HIF-1α is an important regulatory gene in the development of villus in trophoblast invasion such as placenta accreta and previa, while Ki-67 will play a key role in the development of abnormal placenta with its stimulating effect on inflammatory cell development and angiogenesis in accreta and preeclampsia.
Bosentan Ameliorates Diabetic Angiopathy and Nephropathy in Streptozotocin-In...iosrjce
Angiopathy and nephropathy are serious problems encountered in management of diabetes mellitus.
Angiotensin II (AII) and endothelins (ETs) receptors play an important role in the pathogenesis of diabetic
complications. The purpose of this study was to investigate the possible renoprotective and antiangiopathic
effects of the non-selective endothelin (ET) receptor blocker bosentan in type 1 diabetic model of albino wister
rats. These rats were divided into four groups ( each group , N= 12 rats): control group (1), control group (2)
treated with bosentan (50 mg/kg/day), untreated diabetic group (3) and diabetic group (4) treated with
bosentan. Induction of type 1 diabetes mellitus in tested rats was performed by a single injection, in the tail vein,
of 35 mg/kg streptozotozin after overnight fast. Treatment with bosentan was continued for 12 weeks during
which the 24h urine volume, urinary albumin content, urine and plasma levels of creatinine as well as mean
non-invasive blood pressure (mean BP) were assessed at the end of each 4 weeks. At the end of the 12
th week
rats were sacrificed then the thoracic aortae were dissected for assessment of the vasorelaxant effect of
acetylcholine. Diabetic rats showed hyperglycemia, polyuria, albuminuria, elevated mean BP, reduced
response to vasorelaxant effect of ACh. Bosentan significantly reduced albuminuria and lowered elevated mean
BP. In addition the drug restored the normal values of creatinine clearance and improved vascular reactivity to
ACh. The present study suggested a possible renoprotective and aortic vasorelaxant effects by bosentan without
a significant effect on the control of blood glucose. The results of the present study was directed towards a
possible role of bosentan, as a drug acting on Endothelin receptors, in the improvement of diabetic angiopathy and nephropathy.
Search for atoxic cereals: a single blind, cross-over study on the safety of...Enrique Moreno Gonzalez
Cereals of baking quality with absent or reduced toxicity are actively sought as alternative therapy to a gluten-free diet (GFD) for patients with coeliac disease (CD). Triticum monococcum, an ancient wheat, is a potential candidate having no toxicity in in-vitro and exvivo studies. The aim of our study was to investigate on the safety of administration of a single dose of gluten of Tm in patients with CD on GFD.
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
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.
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
Objective: A spinal cord injury (SCI) is damage to the spinal cord either from trauma, loss of its normal blood supply, or compression from tumor or infection. In this study we focused on alterations in the bladder tissue with angiogenic and apoptotic aspects after spinal cord injury.
Study Design: Twenty Wistar Albino rats were categorized as control and SCI groups. At T7-T9 vertebras, a steel rod was dropped from 10 cm to create a spinal cord injury under anesthesia. Rats were decapitated and spinal tissue was processed to measure malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO).
Results: MDA, MPO, epithelial degeneration, vascular dilation, inflammation, VEGF, and APAF-1 expressions in the SCI group were statistically higher than those in the control group. GSH content of the SCI group was statistically lower than that in the control group. In the hematoxylin-eosin–stained sections of the control group, normal histology was observed in bladder tissue. In the SCI group, degeneration epithelial cells, thinned epithelium, increased fibrosis, dilated and congested blood vessels, and hyperplastic endothelial cells were observed. In the control group, VEGF expression was slightly observed in some epithelial cells and vascular cells. In the SCI group, VEGF expression was increased in inflammatory and vascular endothelial cells. For APAF-1 expression, the control group showed no expression. In the SCI group, APAF-1 expression was positive in degenerated epithelial cells and connective tissue cells.
Conclusion: It is thought that the urination reflex was affected due to increased inflammation in the bladder tissue, leading to alterations in the regulation and function of the muscles.
Objective: To investigate the immunohistochemical staining of hypoxia-inducible factor 1-alpha (HIF-1α) and Ki-67 expression in the placenta of pregnant women with placenta previa and placenta accreta.
Study Design: Thirty placentas (10 normotensive, 10 placenta previa, and 10 placenta accreta) were processed for routine histological tissue processing. The biochemical parameters of patients were recorded. Placentas were stained with hematoxylin-eosin and HIF-1α and Ki-67 immunostaining.
Results: Normal histology was observed in placentas of normotensive pregnant women. Placenta previa sections showed increased syncytial knots, intervillous hemorrhage, fibrin accumulation, and hyalinization. In placenta accreta sections, increased syncytial nodes, vascular dilation/congestion, fibrin accumulation, and hyalinization were observed. Normotensive placentas showed no HIF-1α expression. In placenta previa tissues, high HIF-1α expression was observed in vascular endothelial cells, villous stromal cells, and syncytial knots. High HIF-1α expression was recorded in villous stromal cells and cytotrophoblast cells in placenta accreta. In normotensive placental tissues, no Ki-67 expression was observed. In placenta previa sections, high Ki-67 expression was observed mostly in root villi stromal cells and some endothelial cells. High Ki-67 expression was observed mostly in villi stromal cells of placenta accreta.
Conclusion: It is thought that HIF-1α is an important regulatory gene in the development of villus in trophoblast invasion such as placenta accreta and previa, while Ki-67 will play a key role in the development of abnormal placenta with its stimulating effect on inflammatory cell development and angiogenesis in accreta and preeclampsia.
Bosentan Ameliorates Diabetic Angiopathy and Nephropathy in Streptozotocin-In...iosrjce
Angiopathy and nephropathy are serious problems encountered in management of diabetes mellitus.
Angiotensin II (AII) and endothelins (ETs) receptors play an important role in the pathogenesis of diabetic
complications. The purpose of this study was to investigate the possible renoprotective and antiangiopathic
effects of the non-selective endothelin (ET) receptor blocker bosentan in type 1 diabetic model of albino wister
rats. These rats were divided into four groups ( each group , N= 12 rats): control group (1), control group (2)
treated with bosentan (50 mg/kg/day), untreated diabetic group (3) and diabetic group (4) treated with
bosentan. Induction of type 1 diabetes mellitus in tested rats was performed by a single injection, in the tail vein,
of 35 mg/kg streptozotozin after overnight fast. Treatment with bosentan was continued for 12 weeks during
which the 24h urine volume, urinary albumin content, urine and plasma levels of creatinine as well as mean
non-invasive blood pressure (mean BP) were assessed at the end of each 4 weeks. At the end of the 12
th week
rats were sacrificed then the thoracic aortae were dissected for assessment of the vasorelaxant effect of
acetylcholine. Diabetic rats showed hyperglycemia, polyuria, albuminuria, elevated mean BP, reduced
response to vasorelaxant effect of ACh. Bosentan significantly reduced albuminuria and lowered elevated mean
BP. In addition the drug restored the normal values of creatinine clearance and improved vascular reactivity to
ACh. The present study suggested a possible renoprotective and aortic vasorelaxant effects by bosentan without
a significant effect on the control of blood glucose. The results of the present study was directed towards a
possible role of bosentan, as a drug acting on Endothelin receptors, in the improvement of diabetic angiopathy and nephropathy.
Search for atoxic cereals: a single blind, cross-over study on the safety of...Enrique Moreno Gonzalez
Cereals of baking quality with absent or reduced toxicity are actively sought as alternative therapy to a gluten-free diet (GFD) for patients with coeliac disease (CD). Triticum monococcum, an ancient wheat, is a potential candidate having no toxicity in in-vitro and exvivo studies. The aim of our study was to investigate on the safety of administration of a single dose of gluten of Tm in patients with CD on GFD.
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
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.
A Thesis Submitted to the College of Medicine and the Committee of Postgraduate Studies of the University of Al-Mustansiriya in Partial Fulfillment of the Requirements for the Degree of Master of Science in Pharmacology
Efficiency of cape gooseberry in attenuating some biochemical disorders and o...Professor-Dr Hanaa Hassan
In conclusion, the present data indicated the efficacy of CG juice supplementation as an
anti-hepatocellular carcinoma in addition to its ability as a chemosensitizer for ADR treatment. This is
mediated by intracellular pathways, involving improvement the alterations in liver functions as well as
other aspects of HCC, the suppression of oxidative stress and modulation of antioxidant defense
mechanism. Thus, supplementation with edible CG may help in safe application of cancer technology
in medicine as well as in many other aspects of nowadays life. Fractionation guided evaluation could
help in the development of ideal anticancer in the near future.
Antioxidant-mediated up-regulation of OGG1 via NRF2 induction is associated ...Enrique Moreno Gonzalez
Estrogen metabolism-mediated oxidative stress is suggested to play an important role in estrogen-induced breast carcinogenesis. We have earlier demonstrated that antioxidants,
vitamin C (Vit C) and butylated hydroxyanisole (BHA) inhibit 17β-estradiol (E2)-mediated oxidative stress and oxidative DNA damage, and breast carcinogenesis in female August
Copenhagen Irish (ACI) rats. The objective of the present study was to characterize the mechanism by which above antioxidants prevent DNA damage during breast carcinogenesis.
Objective: To evaluate the results of the effect of nebivolol on tibial bone defect and graft application in new bone development in the rat.
Study Design: Thirty Wistar albino rats were divided into 3 groups. In the Control group, tibia bone defect was created without any treatment. In the Defect+ Graft group, allograft treatment was performed by forming a 6 mm tibial bone defect. In the Defect+Graft+ Nebivolol group, alloplastic bone graft was placed in the calvarial bone defect and then nebivolol (0.34 mg/mL solution/day) treatment was intraperitoneally applied for 28 days.
Results: Histopathological examination revealed inflammation in the defect area, congestion in the vessels, degeneration in collagen fibers, and an increase in osteoclast cells. There was an increase in inflammation and blood vessel structure in graft application, and osteoblastic activity matrix formation after reorganization nebivolol application in collagen fibers. Osteonectin expression was positive in the collagen fiber and matrix, starting in the Graft group, in osteoblasts, whereas in the Nebivolol group, osteoblasts increased in osteocytes and new bone formation.
Conclusion: Nebivolol is thought to have a positive effect on osteoinductive bone growth factors and contribute to the cell-matrix interaction, in addition to the supporting effect of the graft with its antioxidative effect.
Keywords: allograft; bone; bone regeneration; disease models, animal; nebivolol; orthopedic procedures; osteonectin; rats; tibia; tibial defect
Gongronema Latifolium A Plant with Cardioprotective Potentialsijtsrd
Gongronema latifolium GL has gained research interest in the field of Medicine. The present study investigated the cardioprotective potentials of the ethanolic and ethyl acetate fraction of the leaves extract of G.L. 18 Male Wistar rats were divided equally into three groups. Group 1 was the control group, and was administered 0.9 normal saline. Group 2 was administered 200mg kg ethanolic leaves extract of GL. Group 3 received 200mg kg ethyl acetate fraction of the leaves extract of GL. Administration was via oral gavage and lasted for 14 days. The rats were sacrificed under chloroform anaesthesia. Blood was collected via cardiac puncture, allowed to clot, and later centrifuged to get serum. Laboratory assays were done for serum concentrations of total cholesterol Tc , total triglycerides Tg , high density lipoprotein HDL-c , low density lipoprotein LDL , malondialedyde MDA , total antioxidant capacity TAC , and total plasma peroxide TPP . The heart, aorta, and kidneys were also harvested for organ weight and histological studies. Administration of GL extracts resulted in an increase p 0.001 serum concentrations of HDL-c and TAC, with a consequent reduction in the serum concentrations of Tg, LDL-c, VLDL, MDA, and TPP. There was no significant p 0.01 change in organ weights of the heart, aorta, and kidneys across the groups. Histology of the blood vessels showed intact layers across the groups. There was no derangement of cellular architecture in the heart and kidney. This study therefore concludes that Gongronema latifolium leaves extract is cardioprotective, and thus provides a basis for the use of this plant as an alternative for the prevention, management or control of cardiovascular diseases. Justin Atiang Beshel | Favour Nyoh Beshel | Clement Oshie Nku | Daniel Udofia Owu "Gongronema Latifolium: A Plant with Cardioprotective Potentials" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-2 , February 2019, URL: https://www.ijtsrd.com/papers/ijtsrd21431.pdf
Paper URL: https://www.ijtsrd.com/medicine/physiology/21431/gongronema-latifolium-a-plant-with-cardioprotective-potentials/justin-atiang-beshel
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...Enrique Moreno Gonzalez
High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is
mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas.
Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed highgrade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients.
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
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).
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.
A Thesis Submitted to the College of Medicine and the Committee of Postgraduate Studies of the University of Al-Mustansiriya in Partial Fulfillment of the Requirements for the Degree of Master of Science in Pharmacology
Efficiency of cape gooseberry in attenuating some biochemical disorders and o...Professor-Dr Hanaa Hassan
In conclusion, the present data indicated the efficacy of CG juice supplementation as an
anti-hepatocellular carcinoma in addition to its ability as a chemosensitizer for ADR treatment. This is
mediated by intracellular pathways, involving improvement the alterations in liver functions as well as
other aspects of HCC, the suppression of oxidative stress and modulation of antioxidant defense
mechanism. Thus, supplementation with edible CG may help in safe application of cancer technology
in medicine as well as in many other aspects of nowadays life. Fractionation guided evaluation could
help in the development of ideal anticancer in the near future.
Antioxidant-mediated up-regulation of OGG1 via NRF2 induction is associated ...Enrique Moreno Gonzalez
Estrogen metabolism-mediated oxidative stress is suggested to play an important role in estrogen-induced breast carcinogenesis. We have earlier demonstrated that antioxidants,
vitamin C (Vit C) and butylated hydroxyanisole (BHA) inhibit 17β-estradiol (E2)-mediated oxidative stress and oxidative DNA damage, and breast carcinogenesis in female August
Copenhagen Irish (ACI) rats. The objective of the present study was to characterize the mechanism by which above antioxidants prevent DNA damage during breast carcinogenesis.
Objective: To evaluate the results of the effect of nebivolol on tibial bone defect and graft application in new bone development in the rat.
Study Design: Thirty Wistar albino rats were divided into 3 groups. In the Control group, tibia bone defect was created without any treatment. In the Defect+ Graft group, allograft treatment was performed by forming a 6 mm tibial bone defect. In the Defect+Graft+ Nebivolol group, alloplastic bone graft was placed in the calvarial bone defect and then nebivolol (0.34 mg/mL solution/day) treatment was intraperitoneally applied for 28 days.
Results: Histopathological examination revealed inflammation in the defect area, congestion in the vessels, degeneration in collagen fibers, and an increase in osteoclast cells. There was an increase in inflammation and blood vessel structure in graft application, and osteoblastic activity matrix formation after reorganization nebivolol application in collagen fibers. Osteonectin expression was positive in the collagen fiber and matrix, starting in the Graft group, in osteoblasts, whereas in the Nebivolol group, osteoblasts increased in osteocytes and new bone formation.
Conclusion: Nebivolol is thought to have a positive effect on osteoinductive bone growth factors and contribute to the cell-matrix interaction, in addition to the supporting effect of the graft with its antioxidative effect.
Keywords: allograft; bone; bone regeneration; disease models, animal; nebivolol; orthopedic procedures; osteonectin; rats; tibia; tibial defect
Gongronema Latifolium A Plant with Cardioprotective Potentialsijtsrd
Gongronema latifolium GL has gained research interest in the field of Medicine. The present study investigated the cardioprotective potentials of the ethanolic and ethyl acetate fraction of the leaves extract of G.L. 18 Male Wistar rats were divided equally into three groups. Group 1 was the control group, and was administered 0.9 normal saline. Group 2 was administered 200mg kg ethanolic leaves extract of GL. Group 3 received 200mg kg ethyl acetate fraction of the leaves extract of GL. Administration was via oral gavage and lasted for 14 days. The rats were sacrificed under chloroform anaesthesia. Blood was collected via cardiac puncture, allowed to clot, and later centrifuged to get serum. Laboratory assays were done for serum concentrations of total cholesterol Tc , total triglycerides Tg , high density lipoprotein HDL-c , low density lipoprotein LDL , malondialedyde MDA , total antioxidant capacity TAC , and total plasma peroxide TPP . The heart, aorta, and kidneys were also harvested for organ weight and histological studies. Administration of GL extracts resulted in an increase p 0.001 serum concentrations of HDL-c and TAC, with a consequent reduction in the serum concentrations of Tg, LDL-c, VLDL, MDA, and TPP. There was no significant p 0.01 change in organ weights of the heart, aorta, and kidneys across the groups. Histology of the blood vessels showed intact layers across the groups. There was no derangement of cellular architecture in the heart and kidney. This study therefore concludes that Gongronema latifolium leaves extract is cardioprotective, and thus provides a basis for the use of this plant as an alternative for the prevention, management or control of cardiovascular diseases. Justin Atiang Beshel | Favour Nyoh Beshel | Clement Oshie Nku | Daniel Udofia Owu "Gongronema Latifolium: A Plant with Cardioprotective Potentials" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-2 , February 2019, URL: https://www.ijtsrd.com/papers/ijtsrd21431.pdf
Paper URL: https://www.ijtsrd.com/medicine/physiology/21431/gongronema-latifolium-a-plant-with-cardioprotective-potentials/justin-atiang-beshel
ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grad...Enrique Moreno Gonzalez
High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is
mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas.
Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed highgrade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients.
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
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).
The role of curcumin in streptozotocin induced hepatic damage and the trans-d...Prof. Hesham N. Mustafa
Diabetic patients frequently suffer from non-alcoholic steatohepatitis. The current study aimed to investigate the role of curcumin and the response of hepatic stellate cells in streptozotocin (STZ)-induced hepatic damage. Sixty male rats were divided into three groups. The normal control injected with a citrate buffer vehicle and the diabetic control group which was injected intraperitoneally (IP) with a single-dose of streptozotocin (50mg/kg body weight) and a diabetic group was treated with an oral dose of curcumin at 80 mg/kg body weight daily for 60 days. Curcumin effectively counteracts oxidative stress-mediated hepatic damage and improves biochemical parameters. Alpha-smooth muscle actin (α-SMA) was significantly reduced, and insulin antibodies showed strong positive immunoreactivity with curcumin administration. These results optimistically demonstrate the potential use of curcumin, which is attributed to its antiradical/antioxidant activities and its potential β-cell regenerative properties. Also, it has the capability to encourage the trans-differentiation of hepatic stellate cells into insulin-producing cells for a period of time. In addition, as it is an anti-fibrotic mediator that inhibits hepatic stellate cell activation and the transition to myofibroblast-like cells, this suggests the possibility of considering curcumin's novel therapeutic effects in reducing hepatic dysfunction in diabetic patients.
Cerebral microdialysis reflects the neuroprotective effect of fractionated pl...Enrique Moreno Gonzalez
Cerebral edema is a well-recognized and potentially fatal complication of acute liver failure (ALF). The effectiveness of treatments that address intracranial hypertension is generally assessed by measuring intracranial pressure (ICP). The aim of this study was to determine the role of cerebral microdialysis in monitoring the efficacy of fractionated plasma separation and adsorption (FPSA) treatment for ALF. We hypothesized that in ALF cerebral microdialysis reflects the benefits of FPSA treatment on cerebral edema before ICP.
Whey protein products and their combination with L-methionine prevent liver f...iosrphr_editor
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).
Hepatoprotective effects of simvastatin on paracetamol -induced hepatic damag...iosrphr_editor
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).
Similar to Liver ischemia/reperfusion injury, a setting in which the functional mass is reduced and the role of PDE5 inhibitor (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.
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.
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
Immunohistochemical Study of the Ameliorative Effect of Vitamin E on Liver Re...Prof. Hesham N. Mustafa
The liver is almost unique in its capacity for regeneration after hepatectomy but the exact mechanisms are not yet fully clarified. Antioxidants have been shown to promote liver regeneration after major hepatectomy. The present study evaluated the ameliorative effect of vitamin E administration on the liver regeneration after different periods of partial hepatectomy (PH) in rats. Fifty-six adult male albino rats were divided into three groups: Control sham operated group; partially hepatectomized group which were divided into three subgroups sacrificed at 1day, 3 days and 7days after the operation respectively; Partially Hepatectomized group with vitamin E pretreatment before PH where the rats were given a daily oral dose of vitamin E until the time of sacrifice of the rats. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and labeling index were demonstrated. After PH, the PCNA positive hepatocytes and the PCNA labeling indices were significantly high after the 1st day and then much decreased after the 3rd day, to be followed by a slight increase at the 7th day. Vitamin E pretreatment in PH rats resulted in a decrease in PCNA positive cells and its labeling indices in the 1st day with a gradual increase in the 3rd and 7th days. Vitamin E has an inhibitory effect in the first 24 hours on liver regeneration followed by stimulatory effect at the third and seventh days after PH. These data indicated that vitamin E pretreatment has an important role in regulation and enhancement of liver regeneration after PH.
Keywords:
Immunohistochemistry; Labeling Index; Vitamin E; Partial Hepatectomy; PCNA
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
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
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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 ).
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
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MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
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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
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Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
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ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Liver ischemia/reperfusion injury, a setting in which the functional mass is reduced and the role of PDE5 inhibitor
1.
2. Liver ischemia/reperfusion injury, a
setting in which the functional mass
is reduced and the role of PDE5
inhibitor
ORIGINAL ARTICLE Eur. J. Anat. 23 (5): 325-332(2019)
Hesham N. Mustafa1
, Gehan A. Hegazy2,3
, Sally A. El Awdan4
, Aliaa Amr
Alamoudi2
1
Anatomy Department, Faculty of Medicine, King Abdulaziz University, Jeddah, KSA, 2
Clinical Biochemistry Depart-
ment, Faculty of Medicine, King Abdulaziz University, Jeddah, KSA, 3
Medical Biochemistry Department, National Re-
search Centre, Cairo, Egypt, 4
Pharmacology Department, National Research Centre, Cairo, Egypt
SUMARY
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 liver
enzymes 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.
Key words: Ischemia/reperfusion injury – Oxidati-
ve stress – Apoptosis – TNF-α – BCL-2
INTRODUCTION
Hepatic I/R (ischemia/reperfusion) injury is a
common complication following surgical procedu-
res such as liver resection and transplantation that
involves a variable period of ischemia, and may
result in complicated medical conditions such as
shock, trauma, or low cardiac output (Ye et al.,
2015). In addition, it may occur during liver surgery
when Pringle’s maneuver (ligation of the hepato-
duodenal ligament) to reduce blood loss is done
325
Submitted: 25 March, 2019. Accepted: 3 June, 2019.
Corresponding author: Dr. Hesham N. Mustafa, M.D. Depart-
ment of Anatomy, Faculty of Medicine, King Abdulaziz Universi-
ty, P.O. Box 80205, Jeddah 21589, Saudi Arabia.
E-mail: hesham977@hotmail.com
Authors’ contributions: All authors participated in the design
of this work and made equal contributions. All authors read and
approved the final manuscript
3. Liver ischemia/reperfusion injury and PDE5 inhibitor role
326
(Freitas et al., 2017).
Ischemia initiates a series of events that cause
necrosis and cellular dysfunction; the reperfusion
of blood flow can paradoxically generate more tis-
sue injury. Excessive inflammatory reaction is con-
sidered as a key mechanism. A complex cascade
of inflammatory mediators is activated by liver
ischemia and reperfusion (Zhai et al., 2011). I/R
injury is mediated by the activation of proinflamma-
tory cytokines such as TNF-α (tumor necrosis fac-
tor alpha), release of free radicals and the accu-
mulation of inflammatory cells, accumulation of
intracellular sodium and calcium, and induction of
hepatocyte apoptosis (Rao et al., 2013).
During hepatic I/R injury, many microvascular
and endothelial alternations occur as initiation of
coagulation cascade, variations in the molecular
vasoactive products such as endothelin (ET) and
NO (nitric oxide), and upregulation of endothelial
adhesion molecules such as ICAM-1 (intracellular
adhesion molecule-1). These alternations are sug-
gested targets for therapeutic strategies (Camara-
Lemarroy et al., 2014). Safe clearance of damaged
cells is the apoptosis (programmed cell death).
BCL-2 family are proteins that are considered as a
non-death signal (antiapoptosis) (Hegazy et al.,
2018).
Phosphodiesterase (PDE) inhibitors are the com-
pounds that inhibit the biosynthesis or actions of
PDEs. PDE inhibitors are currently widely used in
treatment of erectile dysfunction, as well as in pul-
monary arterial hypertension (Sawamura et al.,
2009). PDE inhibitors have protective effects on
myocardial muscles and vascular structures
(Korkmaz-Icoz et al., 2018). The effects of PDE
inhibitors have been widely studied in I/R in diffe-
rent organs. Moreover, PDE is the family of enzy-
mes that adjust the cellular levels of second mes-
sengers, cyclic adenosine monophosphate (cAMP)
and cyclic guanosine monophosphate (Reffelmann
and Kloner, 2009).
Tadalafil (TDF) is a selective and effective inhibi-
tor of PDE5 (phosphodiesterase type-5) that has
been broadly used in the treatment of erectile dys-
function due to its capability to prevent the break of
cGMP, which is the second messenger of NO
(nitric oxide) (Kucuk et al., 2012). The purpose of
this study was to declare the beneficial effect of
tadalafil on hepatic I/R-injury.
MATERIALS AND METHODS
Drugs
Tadalafil was purchased from Lilly Co. and given
via intraperitoneal injection with dose of 10 mg/kg
(Bektas et al., 2016).
Animals
Mature male Wistar albino rats, their weighs ran-
ging from 200 to 250g. They were obtained from
the Animal House. They were preserved in cages
with optimum temperature, 60% humidity under
12h dark and light cycles. Rats were provided
standard pellet diet and water for one week before
the experiment for adaptation.
Ethics Statement
This study was approved by the biomedical
Ethics Research Committee [Reference No 229-
19].
Experimental Design
Forty-eight rats were separated into four groups
(12 each) in this way; Sham group underwent
midline laparotomy only. Tadalafil group administe-
red Tadalafil 10 mg/kg intraperitoneal 45 min befo-
re sham operation (Bektas et al., 2016). Ischemia-
reperfusion (I/R) group, rats exposed to 60 min of
hepatic ischemia, then they were exposed to 60
min of reperfusion (Liu et al., 2016). Tadalafil+ I/R
group rats were subjected to a similar pattern of I/
R after the administration of Tadalafil 10 mg/kg, 45
minutes before ischemia (Bektas et al., 2016).
Surgical Procedure
All surgical procedures were performed under
complete aseptic conditions, and the anesthesia,
with combination of ketamine 100 mg/kg and xyla-
zine 10 mg/kg, administered through intraperito-
neal route (Savvanis et al., 2014). Rats were expo-
sed to midline abdominal incision, liver lobes and
the portal triad identified, and rats subjected to 60
minutes of hepatic ischemia by clamping the portal
triad with a micro-vascular clamp after the bifurca-
te of the right lobe, interrupting the portal triad flow
to the left and median lobes, inducing ischemia for
60 min, and after that the clamp removed to allow
60 min of reperfusion (Hueper et al., 2018). At the
end of the reperfusion period, the blood samples
were collected from the abdominal aorta and biop-
sies were taken from the ischemic hepatic lobes.
Collection for blood samples
Blood was centrifuged (700×g, 4°C, 20 min) for
assessment of liver enzymes.
Liver tissue Extracts
Liver was homogenized in phosphate buffer sali-
ne (PBS) [10%]. The first part was centrifuged at
15000 g for 10 min, and the supernatant was gat-
hered and kept at -80C° to measure oxidative
stress markers and inflammatory cytokines in liver
tissue homogenates. The second part was subjec-
ted to repeated freeze-thaw cycle twice in order to
break the cell membranes, then centrifuged at
5000×g for 5 min and kept at -80C° for the measu-
rement of the other parameters.
Hepatic biochemical parameters in serum
Serum ALT and AST were determined by using
colorimetric assay kits provided by Elabscience,
Houston, Texas, USA, (Catalogues E-BC-K235, E-
4. H. N. Mustafa et al.
327
BC-K236 respectively) in accordance with the ma-
nufacturer’s instructions.
Oxidative stress markers activities in liver tis-
sue homogenates
Estimation of MDA (malondialdehyde) and GSH
(reduced glutathione) levels utilizing colorimetric
assay kits (Catalogues No.MD 25 29, GR 25 11
respectively) according to the manufacturer’s ins-
tructions (Bio Diagnostic, Cairo, Egypt).
Assessment of hepatic cytokines in liver tissue
homogenates
TNF-α (Tumor necrosis factor-α) and IL-6
(interleukin 6) levels were measured using ELISA
(enzyme-linked immunosorbent assay) kit; (TNF-α:
catalogue number RAB0479 Sigma), RayBio Rat
IL-6 ELISA Kit: (IL6: catalogue number ELR-IL6-
001) in accordance with the manufacturer’s ins-
tructions. Measurement of ICAM-1 (Intercellular
Adhesion Molecule-1): quantitative determination
of ICAM-1 was determined by ELISA using Kit pro-
vided by RayBio Rat ICAM-1 (ICAM-1: catalogue
number ELR-ICAM1) according to the manufactu-
rer’s instructions.
Histopathological analysis
Paraffin sections of 5µm thickness prepared, for
each specimen, at least 3-5 slides stained with
Hematoxylin and Eosin (H&E) to examine hepatic
histoarchitecture, periodic acid-Schiff (PAS) to de-
monstrate the glycogen deposition in hepatocytes,
and Masson’s trichrome (MT) for distinguishing
collagen. The examination using Olympus BX53
microscope equipped with an Olympus DP73 ca-
mera (Olympus, Tokyo, Japan) (Mustafa, 2016).
Immunohistochemical study
Using the streptavidin-biotin-peroxidase techni-
que, the endogenous peroxidase activity was eli-
minated using 10% H2O2 for 15min. Sections were
incubated for 1h with primary antibody against
BCL-2 associated X (BAX) protein, a monoclonal
antibody (Dako, Carpinteria, CA, USA; dilution:
1:200; cytoplasmic), as a marker for apoptotic
death. They were similarly incubated with the pri-
mary antibody against tumor necrosis factor alpha
(TNF-α), a mouse monoclonal antibody (Dako; 5-
10 µg/ml; cytoplasmic), as a marker for inflamma-
tory cytokines. Sections were incubated for 20min
in DAB (3, 30-diaminobenzidine) chromogen and
counterstained with Mayer’s hematoxylin. Negative
control sections were prepared by omitting the pri-
mary antibody. Absence of staining was recog-
nized as a negative result (-), while the presence
of brown staining was recognized as a positive
result (+) (Hegazy et al., 2018).
Semi-quantitative assessment of the severity
of the liver damage using the following para-
meters: congestion, hepatocyte vacuolization, si-
nusoidal dilatation and congestion, central vein
dilatation, and loss of the glycogen deposition in
hepatocytes. Microscopic damage was scored as
no change (-), minimal (+), moderate (++), and
severe (+++), for each parameter, and was asses-
sed in a blinded manner (Sahin et al., 2013; Tas
Hekimoglu et al., 2013).
Morphometric analysis
About 30 sections were analyzed at magnifica-
tions ×200 and ×400 with the use of Image-Pro
Plus v6.0 (Media Cybernetics, Maryland, USA) for
area percentage of collagen and BCL-2 and the
optical density (OD) of TNF-α immunopositive cells
(Hegazy et al., 2018).
Statistical analysis
Quantitative data were expressed as mean and
standard deviation of different parameters between
treated groups. Data analyzed using One Way
Analysis of Variance (ANOVA) followed by Tukey’s
posthoc test. All statistical analysis was implemen-
ted using SPSS version 24. The values considered
significant when P<0.05 (Mustafa et al., 2017).
RESULTS
Effect of Tadalafil on survival rate and body
weight of different groups
Neither deaths nor significant changes in body
weight had been documented in each group.
Effect of Tadalafil on serum liver functions
Tadalafil succeeded in significant decrease in
serum levels of ALT in Tadalafil +I/R) when com-
pared with IR group. ALT is considered a vital
diagnostic marker for liver function and Tadalafil
reduced its level by near the normal level of Sham
group (Table 1). Moreover, Tadalafil induced signi-
ficant decrease in serum level of AST in (Tadalafil
+I/R) when compared with IR group (Table 1).
Groups
Sham
N=12
Tadalafil
N=12
I/R
N=12
Tadalafil +I/R
N=12
ALT (U/L) 293.00±71.39
304.33±57.90
1
P= 0.686
2
P= 0.000
491.75±85.35
1
P= 0.000
299.75±.53.26
1
P= 0.809
2
P= 0.000
AST (U/L) 260.50±58.77
268.83±50.59
1
P= 0.863
2
P= 0.000
791.25±126.37
1
P= 0.000
378.25±181.79
1
P= 0.018
2
P= 0.000
Table 1: Effect of Tadalafil on serum liver functions.
Values are Mean± SD: standard deviation. Comparison between groups done by ANOVA followed by LSD post hoc test. 1
P: compared to Sham group.
2
P: compared to I/R (group subjected to ischemia reperfusion injury).
ALT (Alanine transaminase), AST (Aspartate transaminase). U/L unit/ liter.
5. Liver ischemia/reperfusion injury and PDE5 inhibitor role
328
Effect of Tadalafil on TNF alpha, IL-6 and ICAM
-1 levels in liver tissue homogenate TNF alpha,
IL-6 and ICAM-1
Tadalafil achieved significant decrease in the
level of TNF alpha, IL-6 and ICAM-1 in (Icariin +I/
R) when compared with IR group (Table 2).
Effect of Tadalafil on some oxidative stress
markers in liver tissue homogenate
Tadalafil ameliorated oxidative stress by signifi-
cant reduction of lipid peroxidation, as indicated by
decrease of MDA levels, and restoring reduced
glutathione levels but still significantly different
from sham group (Table 3).
Histological Assessment
Tadalafil + I/R group showed majority of the he-
patocytes and blood sinusoids appear preserved
(Fig. 1, Table 4). Also, it showed noticeable incre-
ment in glycogen content in hepatocytes (Fig. 2,
Table 4). In addition, it showed decreased collagen
fibers around the portal areas as well as in the pe-
risinusoidal region (Fig. 3, Table 5).
Immunohistochemical Assessment
I/R showed negative BCL-2 expression, while
Tadalafil + I/R showed positive BCL-2 expression
and area percentage of BCL-2 reactions was signi-
ficantly increased in Tadalafil + I/R group (Fig. 4,
Table 5). I/R group showed strong positive im-
munoreaction for TNF-α in the hepatocytes cyto-
plasm and in the sinusoids wall. Tadalafil + I/R
group showed weak immunoreaction for TNF- α in
in some hepatocytes cytoplasm and in the sinu-
soids wall. Optical density (OD) of TNF-α supports
the descriptive findings (Fig. 5, Table 5).
DISCUSSION
I/R is one of the clear components of liver injury
Groups
Sham
N=12
Tadalafil
N=12
I/R
N=12
Tadalafil+I/R
N=12
TNF-α
Pg/gm liver tissue
1330.25±103.33
1341.08±80.20
1
P= 0. 838
2
P= 0.000
1943.25±2.38
1
P= 0.000
1608.00±.86.76
1
P= 0.000
2
P= 0.000
IL–6
Pg/gm liver tissue
7.25±0.87
7.50±.0.15
1
P= 0.645
2
P= 0.000
28.75±2.38
1
P= 0.000
11.50±0.52
1
P= 0.000
2
P= 0.000
ICAM-1
Pg/gm liver tissue
9.75±0.45
9.65±0.44
1
P= 0.985
2
P= 0.000
39.75±0.2.01
1
P= 0.000
16.25±2.80
1
P= 0.000
2
P= 0.000
Table 2: Effect of Tadalafil on some inflammatory cytokines in liver tissue homogenate.
Values are Mean± SD: standard deviation. Comparison between groups done by ANOVA followed by LSD post hoc test. 1
P: compared to Sham group.
2
P: compared to I/R (group subjected to ischemia reperfusion injury). TNF-α (Tumor Necrosis Factor alpha), IL-6 (Interleuin-6), ICAM-1 (Intracellular
adhesion molecule-1). Pg/gm liver tissue (Picogram/gram liver Tissue).
Groups
Sham
N=12
Tadalafil
N=12
I/R
N=12
Tadalafil +I/R
N=12
Malondialdhyde (MDA)
(Nano mole /mg liver
tissue)
159.25±44.88
164.25±38.93
1
P= 0.744
2
P= 0.000
494.25±85.72
1
P= 0.000
215.25±40.35
1
P= 0.018
2
P= 0.000
Reduced Glutathione
(GSH)
(Micromole/gm liver
tissue)
19.50±1.3.80
19.92±3.18
1
P= 0. 828
2
P= 0.000
9.00±1.28
1
P= 0.000
15.50 ±3.50
1
P= 0.003
2
P= 0.000
Table 3: Effect of Tadalafil on some oxidative stress markers in liver tissue homogenate.
Values are Mean± SD: standard deviation. Comparison between groups done by ANOVA followed by LSD post hoc test. 1
P: compared to Sham group.
2P: compared to I/R (group subjected to ischemia reperfusion injury). TNF-α (Tumor Necrosis Factor alpha), IL-6 (Interleuin-6), ICAM-1 (Intracellular
a
dhesion molecule-1). Pg/gm liver tissue (Picogram/gram liver Tissue).
Sham
N=12
Tadalafil
N=12
I/R
N=12
Tadalafil + I/R
N=12
Congestion -- -- + --
Hepatocyte vacuolization and necrosis -- -- ++ +
Sinusoidal dilatation and congestion -- -- +++ ++
Central vein dilatation -- -- +++ ++
loss of the glycogen deposition in hepatocytes +++ +++ + ++
Table 4: Histopathological findings in the different study groups.
6. H. N. Mustafa et al.
329
that is evidenced in liver transplantation and liver
resection. Other conditions in which I/R occur is
sepsis, hepatic artery ligation, trauma and hemorr-
hagic shock (Liu et al., 2016). Liver I/R injury is
elicited by more than one mechanism, mainly the
oxidative stress that results in damage in various
organs. Injury in liver I/R consists of 2 phases. The
early phase is due to ischemia caused by lack of
oxygen, the late phase due to reperfusion and it is
characterized by the activation of Kupffer cells and
the release of various mediators (Peralta et al.,
2013).
The current study highlights the mechanism of
tadalafil toward the attenuation of liver ischemia.
Serum ALT and AST levels are widely used as
markers of liver cell damage. In this, tadalafil at a
dose of 10 mg/kg ameliorated hepatic I/R injury, as
demonstrated by reduction in AST and ALT levels,
ameliorated oxidative stress status and cytokines’
profile, in addition to decreased histopathological
alterations. These results are in conformity with
other studies that show the beneficial effects of
other phosphodiesterase inhibitors in depleting
elevated ALT and AST in I/R induced liver injury
Fig 1. A: Sham group showed polyhedral hepatocytes
radiating from the central vein (CV), with rounded ve-
sicular nuclei and acidophilic cytoplasm separated by
blood sinusoids (arrow). B: Tadalafil group showed
architecture being nearly similar to sham group. C: I/R
group showed majority of hepatocytes around the cen-
tral vein (CV) appear necrotic while the remaining ap-
peared vacuolated or with acidophilic cytoplasm and
dark nuclei. Also, disorganized hepatic architecture
around the central vein (CV). The central veins and the
blood sinusoids (arrow) are dilated and congested. D:
Tadalafil + I/R group showed most of the hepatocytes
and blood sinusoids (arrow) appear preserved. Some
hepatocytes appeared vacuolated or with acidophilic
cytoplasm and dark nuclei. The central vein (CV) and
some blood sinusoids are still dilated and congested
(H&E, Scale bar: 20 µm).
Fig 2. A: Sham group showed positive PAS reaction of
magenta staining in which glycogen is present within
hepatocytes. B: Tadalafil group showed nearly similar
to sham group. C: I/R group showed decreased glyco-
gen storage in hepatocytes. D: Tadalafil + I/R group
showed marked increment in glycogen content in
hepatocytes (PAS, Scale bar: 20 µm).
Fig 3. A: Sham group showed minimal collagen around
the central vein (arrow). B: Tadalafil group showed
minimal collagen fibers in the portal tract area (arrow).
C: I/R group showed increased deposition of collagen
fibers in the portal tract area (arrow) and in the peris-
inusoidal spaces. D: Tadalafil + I/R group showed de-
creased collagen deposition in the portal tract area
(arrow) and in the perisinusoidal spaces (Masson tri-
chrome, Scale bar: 20 µm).
Fig 4. A: Sham group showed positive BCL-2 expres-
sion (arrow). B: Tadalafil group showed positive BCL-2
expression (arrow). C: I/R group showed minimal BCL-
2 expression (arrow). D: Tadalafil + I/R group showed
decreased collagen deposition in the portal tract area
(arrow) (BCL-2, Scale bar: 20 µm).
7. Liver ischemia/reperfusion injury and PDE5 inhibitor role
330
(Genoves et al., 2014).
Cyclic nucleotides (cAMP and cGMP) are playing
a pivotal role in signal transduction in many phy-
siological processes, as they are working as se-
cond messengers. Their Intracellular levels are
controlled by adenylyl and guanylyl cyclases,
which are used for their synthesis while they are
degraded by PDEs (Gulati and Singh, 2014).
Reactive oxygen species (ROS) are considered
one of the main constituents involved in I/R. The
Cellular antioxidant enzymatic and non-enzymatic
defense system plays a main role in the mitigation
of tissue injury elicited by free radicals. Hepatic
cellular injury occurs because of the ROS's direct
effect on biological components (Sehitoglu et al.,
2015). Eradication of ROS in healthy cells is main-
tained by a protective scavenging system that eli-
minate the excessively released ROS as (CAT),
superoxide dismutase (SOD), and GSH. Oxidative
stress happens due to the excessive release of
ROS and the decreases antioxidant defense sys-
tem (Sheweita et al., 2015).
GSH is oxidized with the enzymatic effect of glu-
tathione peroxidase to remove the ROS, and hen-
ce release oxidized glutathione (GSSG) in the he-
patic cells, which explains the important role of
GSH in protection against oxidative stress (Peralta
et al., 2013).
During I/R, GSH decreases, as the release of
ROS consumes it, leading to further oxidation and
degradation of vital structures in the cell as lipids,
proteins and DNA (Hegazy et al., 2018). In this
study, tadalafil significantly elevated the depleted
GSH level attenuating the oxidative stress elicited
by I/R in rats. These results are in harmony with
previous studies that stated that PDE inhibitors
restoring GSH level (Luo et al., 2015). Lipid peroxi-
dation is another main mediator in the oxidative
stress produced in different organ injuries. Oxida-
tion of the lipids in cellular membranes lead to ce-
llular damage and the end-product in MDA
(Mustafa et al., 2015). In the present study, I/R
injury resulted in an excessive amount of MDA
levels in the liver. The liver MDA level was more
than that of the normal liver, which is in harmony
with other previous studies that showed the signifi-
cant elevation of MDA in ischemic liver (Cakir et
al., 2016).
Tadalafil significantly depleted the elevated MDA
levels in the liver of I/R rats, and attenuated the
lipid peroxidation effectively. From the main sour-
ces of ROS in I/R hepatic injury is the kupffer cells
and the polymorphonuclear neutrophils (Datta et
al., 2013), as their number and activity determines
the severity of oxidative activity. Moreover, the
activated Kupffer cells produce cytokines, espe-
cially TNF-α and IL-1β (Peralta et al., 2013).
In the current study, tadalafil is associated with
some sinusoidal dilatation. This can be attributed
to the fact that this drug is metabolized in the liver
via the cytochrome P450 system (CYP 3A4 and
2C9), and a toxic or immunogenic intermediate
may account for the rare instances of hepatic inju-
Fig 5. A: Sham group showed negative immunoreac-
tion for TNF-α protein expression in the cytoplasm of
hepatocytes (arrow). B: Tadalafil group showed mini-
mal immunoreaction for TNF-α (arrow). C: I/R group
showed strong positive immunoreaction for TNF-α in
the wall of blood sinusoids and in the cytoplasm of he-
patocytes (arrow). D: Tadalafil + I/R group showed
weak immunoreaction for TNF- α in the wall of blood
sinusoids and in the cytoplasm of some hepatocytes
(arrow) (TNF-α, Scale bar: 20 µm).
Sham
N=12
Tadalafil
N=12
I/R
N=12
Tadalafil + I/R
N=12
Area percent of
collagen
0.28 ± 0.04 0.31± 0.02
3.81± 0.98
1
P<0.001
2
P<0.001
1.21 ± 0.6
1
P<0.01
2
P<0.01
3
P<0.001
Area percentage of BCL
-2
4.76 ± 0.02
4.72 ± 0.05
2.32 ± 0.08
1
P<0.001
2
P<0.001
3.64 ± 0.04
1
P<0.001
2
P<0.001
3
P<0.001
Optical density (OD) of
TNF-α
0.84±0.03 0.95±0.01
6.22±0.41
1
P<0.001
2
P<0.001
2.51±0.12
1
P<0.001
2
P<0.001
3
P<0.001
1
P comparison with sham, 2
P comparison with Tadalafil, 3
P comparison with I/R group.
Table 5: Means±SD of the area percent of collagen and BCL-2 in the studied groups.
8. H. N. Mustafa et al.
331
ry (Graziano et al., 2017; Osayame and Ewek,
2011). In support of this, previous studies found
that the tadalafil may be associated with some cy-
toarchitectural distortion, occasional central vein
and portal vessels dilatation (Osayame and Ewek,
2011; Nna et al., 2015; Jarrar and Almansour,
2015).
Local and systemic inflammatory response elici-
ted by I/R is controlled mainly by released cytoki-
nes such as TNF-α, and affect significantly organ
injury (Rao et al., 2013). During hepatic I/R, leu-
kocyte recruitment is visible in liver injury, and ele-
vated expression of ICAM-1 in endothelial cells
promotes leukocyte adhesion and induces clot
formation that changes sinusoidal perfusion
(Camara-Lemarroy et al., 2014). Beside the in-
creased local expression of ICAM-1 after hepatic I/
R, increased expression of ICAM-1 in other distant
organs has been shown, and that explains the
multiorgan failure detected after I/R (Camara-
Lemarroy et al., 2014; Rao et al., 2013).
Conclusion
Tadalafil effects suggest that modulation of the
inflammatory response might be one of the me-
chanisms of tadalafil-mediated hepatoprotection.
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