Ahmet Ozer Sehirli

Protective effects of melatonin, vitamin E and N-acetylcysteine against acetaminophen toxicity in mice: a comparative study

Abstract: Acetaminophen (AA) is a commonly used analgesic and antipyretic drug; however, when used in high doses, it causes fulminant hepatic necrosis and nephrotoxic effects in both humans and experimental animals. It has been reported that the toxic effects of AA are the result of oxidative reactions that take place during its metabolism. In this study we investigated if melatonin, vitamin E or N‐acetylcystein (NAC) are protective against AA toxicity in mice. The doses of the antioxidants used were as follows: melatonin (10 mg/kg), vitamin E (30 mg/kg) and NAC (150 mg/kg). Blood urea nitrogen (BUN), serum creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in blood, and glutathione (GSH), malondialdehyde (MDA), oxidized protein levels and myeloperoxidase (MPO) activity in liver and kidney tissues were measured. BUN and serum creatinine, ALT and AST levels which were increased significantly following AA treatment decreased significantly after pretreatment with either vitamin E, melatonin or NAC; however, they were not reduced to control levels. ALT and AST levels were significantly higher at 4 hr compared with the 24 hr levels after AA administration. However, BUN and creatinine levels were significantly elevated only at 24 hr. GSH levels were reduced while MDA, MPO and oxidized protein levels were increased significantly following AA administration. These changes were reversed by pretreatment with either melatonin, vitamin E or NAC. Liver toxicity was higher at 4 hr, whereas nephrotoxicity appeared to be more severe 24 hr after treatment with AA. Vitamin E was the least efficient agent in reversing AA toxicity while melatonin, considering it was given as at lower dose than either vitamin E or NAC, was the most effective. This may be the result of the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes.

Curcumin Protects Against Ischemia/Reperfusion Injury in Rat Skeletal Muscle

BACKGROUND Curcumin has been shown to decrease ischemia-reperfusion (I/R) injury in kidney or brain tissues. In this study, the effects of curcumin were evaluated in skeletal muscle during I/R injury. MATERIALS AND METHODS Hind limb ischemia was induced by clamping the common femoral artery and vein. After 4 h ischemia, the clamp of the femoral vessels of animals was taken off and the animal underwent 2 h reperfusion. We measured plasma concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) using enzyme-linked immunosorbent assay (ELISA). The right gastrocnemius muscle was harvested and immediately stored at -30°C for the assessment of superoxide dismutase (SOD), catalase (CAT) activities, and measurement of glutathione (GSH), malondialdehyde (MDA), and protein oxidation (PO) levels. Curcumin (100 mg/kg), α-tocopherol, and normal saline (10 mL /kg1) were administered intraperitoneally 1 h prior reperfusion. RESULTS Plasma TNF-α or IL-1β levels increased significantly in I/R group. The plasma levels of these proinflammatory cytokines were reduced in curcumin group. Muscle tissues of I/R groups revealed significantly higher antioxidant enzyme (superoxide dismutase, glutathione peroxidase, catalase) activities, and increased levels of malondialdehyde, nitric oxide, and protein carbonyl content compared with the SHAM group. Levels of these parameters in muscle revealed significant reductions in the I/R + curcumin group compared witho the I/R group. Curcumin has more potent antioxidant activity than vitamin E in the skeletal muscle I/R. CONCLUSION In this study, protective effects of curcumin against skeletal muscle ischemia-reperfusion injury have been revealed. We underscore the necessity of human studies with curcumin that would be hypothetically beneficial preventing skeletal muscle I/R injury.

Protective effect of melatonin against ischemia/reperfusion -induced oxidative remote organ injury in the rat

PurposeOxygen free radicals are considered to be important components involved in the pathophysiological tissue alterations observed during ischemia/reperfusion (I/R). Based on the potent antioxidant effects of melatonin, we investigated the putative protective role of melatonin against I/R-induced oxidative remote organ injury.MethodsWistar albino rats were subjected to 1 h of infrarenal aortic occlusion followed by 1 h of reperfusion to induce I/R damage. Melatonin (10 mg/kg, s.c.) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period (I/R + Mel or I/R groups). At the end of the reperfusion periods, the rats were decapitated and hepatic, ileal, and lung tissue samples were removed for biochemical analyses of: malondialdehyde (MDA), an end product of lipid peroxidation; the glutathione (GSH) levels, a key antioxidant; and the myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to evaluate the liver function. The wet/dry lung weight ratio was calculated to determine the extent of lung damage.ResultsThe results revealed the occurrence of I/R-induced oxidative organ damage, as evidenced by increases in the MDA and MPO activity, and a decrease in GSH. Furthermore the AST, ALT levels, and the wet/dry lung weight ratio, which all increased due to I/R, were all observed to decrease after melationin treatment.ConclusionSince melatonin administration reversed these oxidant responses, it seems likely that melationin has a protective effect against oxidative organ damage induced by I/R.

Melatonin treatment protects against ischemia/reperfusion-induced functional and biochemical changes in rat urinary bladder

Abstract: Reactive oxygen metabolites play important roles in ischemia/reperfusion (I/R) injury in several systems. The aim of this study was to investigate the role of melatonin against I/R injury of the rat urinary bladder. The abdominal aorta was clamped to induce ischemia for 30 min, then the animals were subjected to 60 min of reperfusion. Melatonin (10 mg/kg, i.p.) or the vehicle (control 1% alcohol i.p.) was administered before I/R. After decapitation, the bladder was removed and the tissue was either used for functional studies or stored for measurement of products of lipid peroxidation (LP), glutathione (GSH) levels and myeloperoxidase activity (MPO). Bladder strips were suspended in oxygenated Tyrodes buffer at 37°C and isometric contractions to carbachol (CCh; 10−8–10−4 m) were recorded.

Effects of N-acetylcysteine on regeneration following partial hepatectomy in rats with nonalcoholic fatty liver disease.

PurposeTo investigate the effect of N-acetylcysteine on regeneration following partial hepatectomy in rats with nonalcoholic fatty liver disease (NAFLD).MethodsN-Acetylcysteine was given to seven rats with NAFLD (group 1); physiological saline was given to seven rats with NAFLD (group 2); and physiological saline was given to seven rats with a normal liver (group 3). We performed two-thirds hepatectomy in all rats and removed the remnant liver tissue 48 h later to measure the mitotic index (MI), proliferating cell nuclear antigen, glutathione (GSH), and malondialdehyde (MDA) levels.ResultsMitotic index values were significantly higher in group 1 than in groups 2 and 3, and higher in group 3 than in group 2. Proliferating cell nuclear antigen values were significantly higher in group 1 than in group 2, but no significant difference was found in comparison with group 3. Glutathione values in group 1 were significantly higher than in group 2 and MDA values in group 1 were lower than in group 2. There was no significant difference between groups 1 and 3 in GSH and MDA values, in both the two-thirds hepatectomy and 48-h tissues.ConclusionsN-Acetylcysteine enhanced regeneration after partial hepatectomy in rats with NAFLD. We believe that it exerted this effect through its influence on oxidative stress.

The effect of ursodeoxycholic acid on liver regeneration after partial hepatectomy in rats with non-alcoholic fatty liver disease

Aim:  To investigate the effect of ursodeoxycholic acid (UDCA) on liver regeneration following partial hepatectomy in rats with non‐alcoholic fatty liver disease (NAFLD).

The effect of betulinic acid on TNBS-induced experimental colitis

ABSTRACT: In this study we have investigated the possible protective effect of betulinic acid (BA) on colonic inflammation in rats. Colitis was induced in Sprague-Dawley rats of both sexes by intracolonic administration of 1 ml trinitrobenzene sulphonic acid (TNBS). Colitisinduced rats received orogastrically either betulinic acid (50 mg/kg/day) or vehicle (0.05% DMSO) for 3 days. At the 72nd hour of colitis induction, the rats were decapitated and trunk blood was collected for the measurement of TNF-, IL-1, lactate dehydrogenase (LDH) levels and total antioxidant capacity (AOC). The distal 8 cm of colon were scored macroscopically, and the degree of oxidant damage was evaluated by malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase activity (MPO), collagen content and by histological analysis. Generation of oxidants was evaluated by tissue luminol and lucigenin chemiluminescences (CL). Colitis caused significant increases in the colonic CL values, macroscopic damage scores, MDA, MPO and collagen levels, along with a significant decrease in tissue GSH level. Similarly, serum TNF-, IL-1, as well as LDH were elevated and AOC was reduced in the vehicle-treated colitis group as compared to control group. On the other hand, betulinic acid treatment reversed all these biochemical indices, as well as histopathological alterations induced by TNBS, suggesting that betulinic acid protects the colonic tissue via its radical scavenging and antioxidant activities. KEY WORDS: betulinic acid; colitis; oxidative damage; inflammation; trinitrobenzene sulphonic acid

Efficacy of Pentoxifylline and Tadalafil in Rat Model of Ischemic ColITIS

ABSTRACT Objective: The aim of this study is to investigate the efficacy of tadalafil against pentoxifylline in rat model of ischemic colitis (IC). Material-Methods: Thirty-two Wistar albino rats were subjected to laparotomy and left colon devascularization to create an IC model and then randomly placed into four groups. Group-1 (sham group) was administered 0.9% NaCl following laparotomy, group 2 (control group) was administered 0.9% NaCl following induced IC, group 3 was given pentoxifylline (n = 8), and group 4 was given tadalafil. On the third day; macroscopic findings, Gomellas ischemic area and Wallace scoring, histopathological analysis, and Chiu scoring were performed, and malondialdehyde (MDA) measurement in ischemic colon tissue was carried out through chemical analysis. Results: Significant differences were observed in acidic fluid, bowel dilatation, and serosal change (p < .05). The ischemic area measured 63.3 mm2 in the control group, 2.8 mm2 in the pentoxifylline group (p = .0001), and 2.4 mm2 (p = .0001) in the tadalafil group. A significant difference was seen between the sham group and the control and pentoxifylline groups (p < .01), in terms of Wallace score and Chiu classification. Similarly, a significant difference was determined between the control group and pentoxifylline and tadalafil groups (p < .01), but no significant difference was established between the pentoxifylline group and tadalafil group (p = .33). MDA measurement was found on an average to be 63.7 in the control group, 22.7 in group 3 and 22.8 in group 4 (p = 001). Conclusion: Although tadalafil is superior to pentoxifylline, both drugs are considered to have positive effects.

Captopril protects against burn-induced cardiopulmonary injury in rats

BACKGROUND This study was designed to determine the possible protective effect of captopril treatment against oxidative damage in heart and lung tissues induced by burn injury. METHODS Under ether anesthesia, the shaved dorsum of Wistar albino rats was exposed to 90°C water bath for 10 seconds. Captopril was administered intraperitoneally (10 mg/kg) after the burn injury and repeated twice daily. In the sham group, the dorsum was dipped in a 25°C water bath for 10 seconds. At the end of the 24 hours, echocardiographic recordings were performed, then animals were decapitated and heart and lung tissue samples were taken for the determination of tumor necrosis factor-α (TNF-α) as a pro-inflammatory cytokine, malondialdehyde and glutathione levels and myeloperoxidase, caspase-3, and Na+,K+-ATPase activity in addition to the histological analysis. RESULTS Burn injury caused significant alterations in left ventricular function. In heart and lung tissues, TNF-α and malondialdehyde levels and myeloperoxidase and caspase-3 activities were found to be increased, while glutathione levels and Na+, K+-ATPase activity were decreased due to burn injury. Captopril treatment significantly elevated the reduced glutathione level and Na+, K+-ATPase activity, and decreased cytokine and malondialdehyde levels and myeloperoxidase and caspase-3 activities. CONCLUSION Captopril prevents burn-induced damage in heart and lung tissues and protects against oxidative organ damage.

nNOS expression in the brain of rats after burn and the effect of the ACE inhibitor captopril

OBJECTIVE To investigate the role of endogenous neuronal nitric oxide synthase (nNOS) on brain injury after burn and the effects of the captopril. METHODS Wistar albino rats (200-250 g) were exposed on the dorsal surface to 90°C (burn) or 25°C (sham) water for 10 s. The ACE group was treated with intraperitoneal 10 mg/kg captopril immediately after burn and this treatment was repeated twice daily. At the end of the 24 h brain samples were taken. nNOS was studied in brain areas by immunohistochemistry. RESULTS There was no difference between the cerebellar and hypothalamic areas the nNOS expression of all groups. nNOS expression increased in the frontal cortex, striatum and midbrain in the burn group compared to the control group. In the frontal cortex, nNOS expression significantly decreased after ACE inhibitor treatment (p<0.05). The striatal nNOS of the ACE group significantly increased when compared to the control group (p=0.001). In the midbrain of the animals, nNOS decreased in the ACE group. Hippocampal nNOS expression did not change after burn and significantly increased after ACE inhibitor therapy (p<0.05). CONCLUSIONS Our data showed that the pathophysiological events following burn appear to be related to an acute inflammatory reaction which is associated with nNOS in the frontal cortex, striatum and midbrain, and captopril treatment abrogates the nNOS response in the frontal cortex and midbrain.