Effects of melatonin on streptozotocin-induced diabetic liver injury in rats (original) (raw)
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Oxidative stress in diabetic rats induced by streptozotocin: Protective effects of melatonin
Journal of Pineal Research, 1998
We have studied the effect of the administration of two doses of melatonin (melatonin 100 and melatonin 200 pgkg bw) on diabetes and oxidative stress experimentally induced by the injection of streptozotocin (STZ) in female Wistar rats. STZ was injected as a single dose (60 mg/kg i.p. in buffered citrate solution, pH 4.0) and melatonin (melatonin 100, 100 pg/kgJday i.p.; melatonin 200, 200 pg/kg/day i.p.) beginning 3 days before diabetes induction and continuing until the end of the study (8 weeks). The parameters analysed to evaluate oxidative stress and the diabetic state were a) for oxidative stress, changes of lipoperoxides (i.e., malondialdehyde, MDA) in plasma and erythrocytes and the changes in reduced glutathione (GSH) in erythrocytes and b) for diabetes, changes in glycemia, lipids (triglycerides: TG; total cholesterol: TC; HDL-cholesterol, HDL-c), percentage of glycosylated hemoglobin (Hb%), and plasma fructosamine. The injection of STZ caused significant increases in the levels of glycemia, percentage of glycosylated hemoglobin, fructosamine, cholesterol, triglycerides, and lipoperoxides in plasma and erythrocytes, whereas it decreased the levels of HDL-c and the GSH content in erythrocytes. The melatonin 100 dose reduced significantly all these increases, except the percentage of glycosylated hemoglobin. With regard to the decreases of plasma HDL-c and GSH content in erythrocytes, this melatonin dose returned them to normal levels. The melatonin 200 dose produced similar changes, though the effects were especially noticeable in the decrease of glycemia (55% vs. diabetes), percentage of hemoglobin (P < 0.001 vs diabetes), and fructosamine (3 1 % vs. diabetes). This dose also reversed the decreases of HDL-c and GSH in erythrocytes. Both doses of melatonin caused significant reduction of the percentage of glycosylated hemoglobin in those groups that were non-diabetic. These illustrate the protective effect of melatonin against oxidative stress and the severity of diabetes induced by STZ. In particular, this study confirms two facts: 1) the powerful antioxidant action of this pineal indole and 2) the importance of the severity of oxidative stress to maintain hyperglycemia and protein glycosylation, two pathogenetic Cornerstones indicative of diabetic complications. Melatonin reduces remarkably the degree of lipoperoxidation, hyperglycemia, and protein glycosylation, which gives hope to a promising perspective of this product, together with other biological antioxidants, in the treatment of diabetic complications where oxidative stress, either in a high or in a low degree, is present.
Journal of Clinical Research & Bioethics, 2016
Objective: To evaluate the therapeutic efficacy of exogenous melatonin (MEL) on hepato-renal tissue in a diabetic rat model. Methodology: Streptozotocin (STZ) was used to establish diabetic rat model. Diabetes was confirmed by monitoring the blood glucose level, animals having glucose level above 250 mg/dl were considered as diabetic and were divided into six different groups. Model control group, diabetic group, melatonin treatment to diabetic rats, melatonin per se group, glibenclamide (a standard hypoglycemic drug) treatment to diabetic rats and glibenclamide (standard control) alone respectively. The model control was given 0.5 ml (0.1 M) citrate buffer, experiment was conducted for one month. After the completion of experiment, rats were sacrificed. Blood was collected and centrifuged at 3000 rpm for 10 minutes to obtain the serum. Serum was kept at-800c for further analysis of liver and renal function tests and lipid profile. Liver and kidney tissues were weighed, fixed in Bouin's fixative for histopathological studies. Further tissues were processed for Lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Major findings: Administration of MEL to STZ induced diabetic rat showed a significant decrease of lipid peroxidation (TBARS) in kidney and liver tissue comparable to the control and GLIBEN group of rats. In addition MEL prevented the decrease in antioxidative enzyme parameters viz. superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) of hepato-renal tissues. Parameters of liver functions (alanine amino transaminase (ALT), aspartate amino transaminase (AST) and alkaline phosphatase (ALP) and renal function (urea, uric acid and creatinine) were noted restored following MEL treatment. MEL administration further maintained the normal levels of lipid profiles i.e., triglyceride, cholesterol, low and high density lipoprotein (LDL, HDL) to that of the control group of rats. Histological architecture of liver and kidney tissues were noted repaired and rescued as judged by cellularity of hepatocytes and renal cells. Conclusion: The present finding strongly indicates the protective effect of exogenous melatonin for hepato-renal tissues form the damages and impairment observed and noted in the experimentally induced STZ male rat model.
Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of diabetic rats
Journal of Pineal Research, 2001
Although melatonin has been established as a free radical scavenger and antioxidant, its effects in diabetes have not been thoroughly investigated. The purpose of this study, therefore, was to investigate the effects of melatonin administration on lipid peroxidation and antioxidant status in streptozotocin (STZ)-induced diabetes in rats. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) in erythrocytes and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were compared in 3 groups of 10 rats each [control non-diabetic rats (group I), untreated diabetic rats (group II) and diabetic rats treated with melatonin (group III)]. In the study groups, diabetes developed 3 days after intraperitoneal (i.p.) administration of a single 60-mg/kg dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10-mg/kg i.p. dose of melatonin per day. After 6 wk, the rats in groups II and III had significantly lower body weights and significantly higher blood glucose levels than the rats of group I (PB 0.001 and P B 0.001, respectively). There were no significant differences in body weight or blood glucose levels between groups II and III. MDA levels in untreated diabetic rats were higher than those in control group rats and in diabetic rats treated with melatonin (PB 0.01 and PB 0.05, respectively). However, MDA levels in diabetic rats treated with melatonin were not different from those of the control group. The GSH, GSH-Px and SOD levels of untreated diabetic rats were significantly lower than those of the control group (P B 0.02, P B0.002 and P B 0.05, respectively). In group III, however, melatonin prevented decreases in the thiol antioxidant and the associated enzymes, and so these levels were not significantly different from those in the control group. These results confirm the presence of oxidative stress in STZ-induced experimental diabetes and indicate the beneficial free radical-scavenging and antioxidant properties of melatonin.
Melatonin ameliorates oxidative damage in hyperglycemia-induced liver injury
Clinical & Investigative Medicine, 2012
Purpose: Melatonin (N-acetyl-5-methoxy-tryptamine) is synthesized mainly by the pineal gland and its antioxidant properties have been demonstrated both in short and long term studies. Our aim was to clarify the effects of hyperglycemia and to administer melatonin on lipid peroxidation, protein oxidation and oxidative DNA damage in rat. Methods: Malondialdehyde (MDA), protein carbonyl (PCO) and total thiol (T-SH) levels were determined in plasma and liver tissue, glutathione (GSH) levels in erythrocyte and liver tissue, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in plasma and liver. Thirty-eight male Wistar rats were divided into four groups: 1 - injected with saline (n = 8), 2 - injected with melatonin (n = 10), 3 - injected with STZ (65 mg/kg, i.p.) (diabetic group) (n = 10) and 4 - injected with melatonin (10 mg/kg/day, i.p.) and STZ (65 mg/kg, i.p.) (n = 10) for 8 weeks (diabetic+ melatonin group). Colorimetric methods were used to determine the level of the oxidative stress ...
Melatonin attenuates metabolic disorders due to streptozotocin-induced diabetes in rats
European Journal of Pharmacology, 2007
Enhanced oxidative stress and impairments in nitric oxide synthesis and bioavailability are of considerable importance in the pathogenesis of diabetic vascular diseases. The aim of the present work was to evaluate the metabolic effects of pharmacological doses of the melatonin, a known antioxidant, on streptozotocin-induced diabetic damage in rats. We investigated the indolamine's influence on the cellular redox-balance, nitric oxide (NO) level, and the activities of antioxidative defence enzymes, as well as the activities of enzymes involved in phase II detoxication and NADPH-generating pentose phosphate pathway. Blood glucose, glycated hemoglobin, bilirubin, as well as plasma alanine aminotransferase activities increased and body weight was reduced in rats with streptozotocin-induced (60 mg/kg, i.p.) diabetes (25 days). The NO level was markedly increased in diabetic plasma (by 50%) and aortic tissue (by 30%). The hyperglycemia resulted in reduced activities of glutathione peroxidase (by 25%), catalase (by 20%), glucose-6-phosphate dehydrogenase (by 55%) and transketolase (by 40%) in liver tissue of diabetic animals. Melatonin treatment (10 mg/kg, 18 days) did not influence the level of hyperglycemia or glycated hemoglobin and it had little effect on the activities of antioxidative enzymes. However, melatonin markedly reversed the activities of glucose-6-phosphate dehydrogenase and transketolase in liver tissue of diabetic rats. The most pronounced effect of the melatonin administration was the prevention of an increase in nitric oxide levels in blood plasma and aortic tissue during diabetes. In in vitro experiments, nitrosomelatonin formation in the presence of nitrosodonors was observed. This implies that melatonin might operate as an NO scavenger and carrier. Thus, melatonin treatment may have some beneficial effects in controlling diabetic vascular complications.
Protective effect of melatonin on β-cell damage in streptozotocin-induced diabetes in rats
Acta Histochemica, 2003
The aim of the present study was the evaluation of possible protective effects of melatonin against β-cell damage in streptozotocin-induced diabetes in rats. Malondialdehyde levels and glutathione peroxidase activity were measured in pancreatic homogenates. Pancreatic β-cells were examined by immunohistochemical methods. Streptozotocin was injected intraperitoneally at a single dose of 60 mg/kg for induction of diabetes. Melatonin (200 µg/kg/day, ip) was injected for 3 days prior to administration of streptozotocin; these injections were continued until the end of the study (4 weeks). Streptozotocin induced a significant increase in malondialdehyde levels (p < 0.01) and a significant decrease in glutathione peroxidase activity (p < 0.05) in pancreatic tissue. Degeneration of islet cells and weak immunohistochemical staining of insulin was observed in diabetic rats. Treatment of diabetic rats with melatonin markedly reduced malondialdehyde production (p < 0.05) and increased glutathione peroxidase activity (p < 0.01) without affecting hyperglycemia. Increased staining of insulin and preservation of islet cells were apparent in the melatonin-treated diabetic rats. These data suggest that melatonin treatment has a therapeutic effect in diabetes by reduction of oxidative stress and preservation of pancreatic β-cell integrity.
Protective effect of melatonin on beta-cell damage in streptozotocin-induced diabetes in rats
Acta histochemica, 2003
The aim of the present study was the evaluation of possible protective effects of melatonin against β-cell damage in streptozotocin-induced diabetes in rats. Malondialdehyde levels and glutathione peroxidase activity were measured in pancreatic homogenates. Pancreatic β-cells were examined by immunohistochemical methods. Streptozotocin was injected intraperitoneally at a single dose of 60 mg/kg for induction of diabetes. Melatonin (200 µg/kg/day, ip) was injected for 3 days prior to administration of streptozotocin; these injections were continued until the end of the study (4 weeks). Streptozotocin induced a significant increase in malondialdehyde levels (p < 0.01) and a significant decrease in glutathione peroxidase activity (p < 0.05) in pancreatic tissue. Degeneration of islet cells and weak immunohistochemical staining of insulin was observed in diabetic rats. Treatment of diabetic rats with melatonin markedly reduced malondialdehyde production (p < 0.05) and increased glutathione peroxidase activity (p < 0.01) without affecting hyperglycemia. Increased staining of insulin and preservation of islet cells were apparent in the melatonin-treated diabetic rats. These data suggest that melatonin treatment has a therapeutic effect in diabetes by reduction of oxidative stress and preservation of pancreatic β-cell integrity.
DNA protective and antioxidative effects of melatonin in streptozotocin-induced diabetic rats
TURKISH JOURNAL OF BIOLOGY, 2015
Diabetes mellitus is a chronic disease characterized by elevated blood sugar levels. In diabetic patients, oxidative stress induced by the presence of excessive free radicals is closely associated with chronic inflammation, leading to potential tissue damage. Melatonin (MEL) is a compound synthesized by the pineal gland and a scavenger of free radicals. The aim of this study was to research the effects of MEL on oxidative stress and its DNA protective effects in streptozotocin-induced diabetic rats. In total, 32 rats were equally divided into four experimental groups: control, melatonin, diabetic, and diabetic + melatonin. A single dose of streptozotocin (60 mg/kg) was given by intraperitoneal route to induce experimental diabetes. MEL (10 mg/kg daily) was administrated to rats by intraperitoneal route for 6 weeks. Oxidative stress parameters were evaluated in rat liver, kidney, brain, and pancreas tissues. Body weight, plasma glucose, and HbA 1c levels were studied. DNA damage was analyzed by comet assay in lymphocytes, while % tail DNA and mean tail moment parameters were evaluated. The study results indicate that the intraperitoneal administration of 10 mg/kg MEL over 6 weeks may cause amelioration in oxidative stress parameters against diabetes, leading to beneficial effects based on % tail DNA and mean tail moment parameters in rat lymphocytes.
Journal of diabetes and metabolic disorders, 2017
Diabetes mellitus (DM) is a serious chronic disease, with multiple complications including hepatopathy associated with imbalance of the oxidative status. The purpose of this study is to observe possible protective effects of vitamin-D and melatonin on glucose profile, antioxidant-oxidant status, lipid peroxidation, and histopathological protection of the liver in streptozotocin-induced diabetic rats. Eighty three male albino rats were divided into nine groups as follows:( = 10) Normal control rats;( = 8) were normal rats treated with melatonin only;( = 10) were normal rats treated with vitamin D only;( = 9) were diabetic rats, which received no medications;( = 8) were diabetic rat treated with insulin only;( = 10) were diabetic rats treated with melatonin only;( = 9) were diabetic rats treated with melatonin and insulin;( = 9) were diabetic rats treated with vitamin D only;( = 10) were diabetic rats treated with vitamin D and insulin. Two months post treatment, blood was collected t...
Asian Journal of Andrology, 2006
To examine the effects of melatonin treatment on lipid peroxidation (LPO) and the activities of antioxidant enzymes in the testicular tissue of streptozotocin (STZ)-induced diabetic rats. Methods: Twenty-six male rats were randomly divided into three groups as follows: group I, control, non-diabetic rats (n = 9); group II, STZ-induced, untreated diabetic rats (n = 8); group III, STZ-induced, melatonin-treated (dose of 10 mg/kg·day) diabetic rats (n = 9). Following 8-week melatonin treatment, all rats were anaesthetized and then were killed to remove testes from the scrotum. Results: As compared to group I, in rat testicular tissues of group II , increased levels of malondialdehyde (MDA) (P < 0.01) and superoxide dismutase (SOD) (P < 0.01) as well as decreased levels of catalase (CAT) (P < 0.01) and glutathione peroxidase (GSH-Px) (P > 0.05) were found. In contrast, as compared to group II, in rat testicular tissues of group III, levels of MDA decreased (but this decrease was not significant, P > 0.05) and SOD (P < 0.01) as well as CAT (P < 0.05) increased. GSH-Px was not influenced by any of the treatment. Melatonin did not significantly affect the elevated glucose concentration of diabetic group. At the end of the study, there was no significant difference between the melatonin-treated group and the untreated group by means of body and testicular weight. Conclusion: Diabetes mellitus increases oxidative stress and melatonin inhibits lipid peroxidation and might regulate the activities of antioxidant enzymes of diabetic rat testes. (Asian J Androl 2006 Sep; 8: 595-600) Effect of melatonin on diabetic rat testis http://www.asiaandro.com; aja@sibs.ac.cn