Ahmet Özer Şehirli

Melatonin protects against endosulfan‐induced oxidative tissue damage in rats

Abstract:  Endosulfan is a chlorinated cyclodiene insecticide which induces oxidative stress. In this study, we investigated the possible protective effect of melatonin, an antioxidant agent, against endosulfan (Endo)‐induced toxicity in rats. Wistar albino rats (n = 8) were administered endosulfan (22 mg/kg/day orally) followed by either saline (Endo group) or melatonin (10 mg/kg/day, Endo + Mel group) for 5 days. In other rats, saline (control group) or melatonin (10 mg/kg/day, Mel group) was injected for 5 days, following corn oil administration (vehicle of endosulfan). Measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were performed in liver and kidney. Furthermore, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine levels, lactate dehydrogenase (LDH) activity were measured in the serum samples, while tumor necrosis factor‐α (TNF‐α), interleukin‐β (IL‐β) and total antioxidant capacity (AOC) were assayed in plasma samples. Endosulfan administration caused a significant decrease in tissue GSH and plasma AOC, which was accompanied with significant rises in tissue MDA and collagen levels and MPO activity. Moreover, the proinflammatory mediators (TNF‐α and IL‐β), LDH activity, AST, ALT, creatinine and BUN levels were significantly elevated in the endosulfan‐treated rats. On the other hand, melatonin treatment reversed all these biochemical alterations induced by endosulfan. Our results suggest that oxidative mechanisms play an important role in endosulfan‐induced tissue damage and melatonin, by inhibiting neutrophil infiltration, balancing oxidant–antioxidant status and regulating the generation of inflammatory mediators, ameliorates oxidative organ injury as a result of endosulfan toxicity.

Melatonin protects against ischemic heart failure in rats

Ischemic injury, which occurs as a result of sympathetic hyperactivity, plays an important role in heart failure. Melatonin is thought to have antiatherogenic, antioxidant, and vasodilatory effects. In this study, we investigated whether melatonin protects against ischemic heart failure (HF). In Wistar albino rats, HF was induced by left anterior descending (LAD) coronary artery ligation and rats were treated with either vehicle or melatonin (10 mg/kg) for 4 weeks. At the end of this period, echocardiographic measurements were recorded and the rats were decapitated to obtain plasma and cardiac tissue samples. Lactate dehydrogenase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lysosomal enzymes (β‐D‐glucuronidase, β‐galactosidase, β‐D‐N‐acetyl‐glucosaminidase, acid phosphatase, and cathepsin‐D) were studied in plasma samples, while malondialdehyde and glutathione levels and Na+, K+‐ATPase, caspase‐3 and myeloperoxidase activities were determined in the cardiac samples. Sarco/endoplasmic reticulum calcium ATPase (SERCA) and caveolin‐3 levels in cardiac tissues were evaluated using Western blot analyses. Furthermore, caveolin‐3 levels were also determined by histological analyses. In the vehicle‐treated HF group, cardiotoxicity resulted in decreased cardiac Na+, K+‐ATPase and SERCA activities, GSH contents and caveolin‐3 levels, while plasma LDH, CK, and lysosomal enzyme activities and cardiac MDA and Myeloperoxidase (MPO) activities were found to be increased. On the other hand, melatonin treatment reversed all the functional and biochemical changes. The present results demonstrate that Mel ameliorates ischemic heart failure in rats. These observations highlight that melatonin is a promising supplement for improving defense mechanisms in the heart against oxidative stress caused by heart failure.

Caffeic acid phenethyl ester (CAPE) prevents methotrexate-induced hepatorenal oxidative injury in rats

Objectives  This study aimed to investigate the antioxidant and anti‐inflammatory effects of caffeic acid phenethyl ester (CAPE) on the methotrexate (MTX)‐induced hepatorenal oxidative damage in rats.

Protective Effects of Lycopene on Cerulein-Induced Experimental Acute Pancreatitis in Rats

BACKGROUND The purpose of our study was to evaluate the protective effect of the strong antioxidant and anti-inflammatory agent, lycopene, on oxidative stress in a rat model of cerulein-induced acute edematous pancreatitis. METHODS Sprague-Dawley rats were pretreated with lycopene (50 mg/kg, i.p.) or saline 15 min before cerulein was given 20 μg/kg (i.p.) at 1-h intervals within 4 h. Twelve hours after cerulein or saline injections, the animals were killed by decapitation. Blood samples were collected to analyze amylase, lipase, and proinflammatory cytokines (TNF-α and IL-1ß). Pancreatic tissues were taken for the determination of tissue glutathione (GSH) and malondialdehyde (MDA) levels, Na(+)/K(+)-ATPase, and myeloperoxidase (MPO) activities. Tissue samples were also examined histologically. RESULTS Acute pancreatitis caused significant decrease in tissue GSH levels and Na(+)/K(+)-ATPase activity, while pancreatic MDA levels and MPO activity were increased. Furthermore, TNF-α, IL-1ß, and amylase lipase levels were also significantly increased. On the other hand, lycopene pretreatment reserved all these biochemical indices as well as histopathologic alterations that were induced by cerulein. CONCLUSIONS According to the results, lycopene protects the pancreatic tissues from oxidative damage induced by cerulein, and this effect possibly involves the inhibition of neutrophil infiltration and lipid peroxidation. These results suggest that high dietary intake of tomatoes may have protective effects against acute pancreatitis.

Protective Effects of Pycnogenol against Ischemia Reperfusion-Induced Oxidative Renal Injury in Rats

Introduction. Oxygen free radicals are involved in pathophysiology of ischemia/reperfusion (I/R) injury. This study was designed to assess the possible protective effect of pycnogenol (PYC) against I/R-induced oxidative renal damage. Materials and methods. Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. PYC (10 mg kg−1, i.p.) or saline was administered at 15 min prior to ischemia and immediately before the reperfusion period. At the end of the 3 h, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) activity were measured in the serum samples, while proinflammatory cytokines, TNF-α, IL-1β, and IL-6 levels were assayed in plasma samples. Kidney samples were taken for the determination of tissue malondialdehyde (MDA), glutathione (GSH) levels, Na+,K+-ATPase, and myeloperoxidase (MPO) activities, and the extent of tissue injury was analyzed microscopically. Results. Ischemia/reperfusion caused a significant decrease in tissue GSH level and Na+,K+-ATPase activity, which was accompanied with significant increases in the renal MDA level and MPO activity. Similarly, serum creatinine and BUN levels, as well as LDH and IL-1β, IL-6, and TNF-α levels, were elevated in the saline-treated I/R group as compared to saline-treated control group. On the other hand, PYC treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by I/R. Conclusions. Findings of the present study suggest that pycnogenol exerts renoprotective effects, via its free radical scavenging and antioxidant activities, that appear to involve the inhibition of tissue neutrophil infiltration.

Montelukast, a selective cysteinyl leukotriene receptor 1 antagonist, reduces cerulein-induced pancreatic injury in rats.

Objectives: This study was designed to evaluate the protective effect of the cysteinyl leukotriene receptor antagonist montelukast against pancreatic injury during acute pancreatitis. Methods: Acute pancreatitis was induced in rats by 20-&mgr;g/kg (intraperitoneal) cerulein given at 1-hour intervals within 4 hours. Montelukast was administered intraperitoneally at a dose of 10 mg/kg 15 minutes before the first cerulein injection. Six hours after the cerulein or saline injections, the animals were killed by decapitation. Blood samples were collected to analyze amylase, lipase, and the proinflammatory cytokines tumor necrosis factor &agr; and interleukin 1&bgr;. Pancreas tissues were taken for the determination of tissue glutathione and malondialdehyde levels and Na+,K+-adenosine triphosphatase and myeloperoxidase activities. The extent of tissue injury was analyzed microscopically. Results: Acute pancreatitis caused significant decreases in tissue glutathione level and Na+,K+-adenosine triphosphatase activity, which were accompanied with significant increases in the pancreatic malondialdehyde level, myeloperoxidase activity, and plasma cytokine level. On the other hand, montelukast treatment reversed all these biochemical indices and histopathological alterations that were induced by cerulein. Conclusions: These results suggest that cysteinyl leukotrienes may be involved in the pathogenesis of acute pancreatitis and that the cysteinyl leukotriene receptor antagonist, montelukast, might be of therapeutic value for treatment of acute pancreatitis.

Antioxidant and Anti-inflammatory Effects of Curcumin Against Hepatorenal Oxidative Injury in the Experimental Sepsis Model Created in Rats

BACKGROUND To investigate the effects of curcumin, an antioxidant and anti-inflammatory agent, on free oxygen radicals and lipid peroxidation in an experimental sepsis model, as well as to determine the role of curcumin in preventing hepatorenal tissue damage caused by sepsis. METHODS The rats were randomly divided into three groups (n=8) as follows: control group (group 1); sepsis group (group 2); and sepsis + curcumin group (group 3). Sepsis was created using the cecal ligation and perforation (CLP) method. Curcumin was administered intraperitoneally (200 mg/kg) in two equal doses just after the perforation and at twelve hours post-perforation. RESULTS Serum TNF-a and IL-1ß, and tissue MDA and MPO values were higher, whereas tissue GSH and Na+/K+-ATPase values were lower, in group 2 as compared to group 1. These values in group 3 were the inverse of those in group 2. As compared to group 1, histopathological evaluation of group 2 showed damaged hepatocytes, glomeruli, and tubules, whereas the damage was significantly reduced in group 3 as compared to group 2. CONCLUSION The strong antioxidant and anti-inflammatory effects of curcumin against potential hepatorenal damage were shown using an experimental sepsis model in rats.

Does alfa lipoic acid prevent liver from methotrexate induced oxidative injury in rats

PURPOSE To determine the antioxidant and anti-inflammatory effects of alfa lipoic acid (ALA) on the liver injury induced by methotrexate (MTX) in rats. METHODS Thirty two rats were randomly assigned into four equal groups; control, ALA, MTX and MTX with ALA groups. Liver injury was performed with a single dose of MTX (20 mg/kg) to groups 3 and 4. The ALA was administered intraperitonealy for five days in groups 2 and 4. The other rats received saline injection. At the sixth day the rats decapitated, blood and liver tissue samples were removed for TNF-α, IL-1β, malondialdehyde, glutathione, myeloperoxidase and sodium potassium-adenosine triphosphatase levels measurement and histological examination. RESULTS MTX administration caused a significant decrease in tissue GSH, and tissue Na+, K+ ATPase activity and which was accompanied with significant increases in tissue MDA and MPO activity. Moreover the pro-inflammatory cytokines (TNF-α, IL- β) were significantly increased in the MTX group. On the other hand, ALA treatment reversed all these biochemical indices as well as histopathological alterations induced by MTX. CONCLUSION Alfa lipoic acid ameliorates methotrexate induced oxidative damage of liver in rats with its anti-inflammatory and antioxidant effects.

Beneficial effects of alpha lipoic acid on cerulein-induced experimental acute pancreatitis in rats

BACKGROUND The present study aimed to determine the effects of alpha lipoic acid (ALA) on blood and tissue biochemical parameters, as well as tissue histopathology, in an experimental rat model of cerulein-induced acute pancreatitis (AP). METHODS Three groups consisting of eight rats each were used, as follows: Group 1, controls; Group 2, cerulein-induced pancreatitis group treated with saline; and Group 3, cerulein-induced pancreatitis group treated with ALA. AP was induced by intraperitoneal administration of cerulein (20 µg/kg) 4 times at 1-hour intervals. The animals were decapitated 12 hours after the last dose of cerulein. Blood amylase, lipase, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α levels, pancreas tissue glutathione (GSH) and malondialdehyde (MDA) levels, as well as myeloperoxidase (MPO) and Na+-K+-ATPase activity were measured. Pancreatic tissue samples were also evaluated histopathologically under a light microscope. RESULTS While plasma amylase, lipase, IL-1ß, and TNF-α levels, and tissue MDA and MPO levels significantly increased in rats with cerulean-induced AP, tissue GSH and Na+-K+-ATPase activity significantly reduced. These changes were reversed and improved with ALA treatment. CONCLUSION Our findings suggest that ALA may significantly reduce morbidity and mortality by preventing organ dysfunction induced by free radicals in the pancreas.

The effects of citalopram and low-dose risperidone on memory and anxiety in rats subjected to chronic immobilization stress

ABSTRACT OBJECTIVES: Many clinical reports describe the beneficial effects of low-dose atypical antipsychotic added to the antidepressants in the management of anxiety disorders. The aim of this study was to evaluate the effect of low-dose atypical antipsychotic when added to antidepressant treatment on cholinergic M1 receptor expression in the hippocampus and amygdale region in learning and cognitive disorders caused by anxiety. METHODS: The treatments were administered by using different test models on memory, learning, and anxiety, as well as the effect on muscarinic M1 receptor expression levels were assessed. Citalopram (10 mg/kg/sc) and combination [citalopram and risperidone (1 mg/kg/sc)] treatments were applied after stress induction using the immobilization model in rats. Animals groups were randomly divided as: control, stress, stress + citalopram, and stress + combination treatment group. Rats in stress groups were immobilized in cages for 4 h a day for 15 days. On days 1–5, groups were subjected to Morris water maze (MWM), open field, and elevated plus maze (EPM) tests. RESULTS: MWM test results have shown that citalopram induces an anxiolytic effect. Low-dose risperidone treatment has increased the antidepressant-like activity of citalopram in all tests. In OFT the number of squares that rats were circulating on the plane was increased and the time spent by the rats on the maze platform was also increased in MWM. In addition to this, the time spent by the rats on the open arms of the EPM test were also increased. Since the combined treatment increased the discovery of the environment and the active behaviour in tests; all those reflected the increase in general activity. Findings also suggest that treatments may play an effective role in altering the expression level of M1 receptors which are effective in learning and recalling information in the amygdale and the hippocampus. Combination treatment has been shown to provide a meaningful correction of stress-induced memory and learning functions. CONCLUSIONS: These findings indicate that combination treatment may help reduce the stress-induced impairments in cognitive functions.