Biochemical and Histopathological Inflections in Hepato-renal Tissues of Streptozotocin (STZ) Induced Diabetic Male Rats: Impact of Exogenous Melatonin Administration

S. Rai, Y. A. Hajam, M. Basheer, H. Ghosh
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引用次数: 14

Abstract

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.
链脲佐菌素(STZ)诱导的雄性糖尿病大鼠肝肾组织生化和病理变化:外源性褪黑素的影响
目的:探讨外源性褪黑素(MEL)对糖尿病大鼠模型肝肾组织的治疗作用。方法:采用链脲佐菌素(STZ)建立糖尿病大鼠模型。通过监测血糖水平确诊糖尿病,血糖水平高于250 mg/dl的动物被视为糖尿病,并分为6组。模型对照组、糖尿病组、糖尿病大鼠褪黑素治疗组、褪黑素本身组、糖尿病大鼠格列本脲(标准降糖药物)治疗组和单独格列本脲(标准对照)组。模型对照组给予0.5 ml (0.1 M)柠檬酸缓冲液,实验1个月。实验结束后,处死大鼠。采集血液,在3000转/分离心10分钟得到血清。血清保存在-800℃,用于进一步分析肝肾功能和血脂。称重肝脏和肾脏组织,用Bouin固定液固定,进行组织病理学研究。进一步处理组织脂质过氧化(LPO)、还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)。主要发现:与对照组和GLIBEN组相比,STZ诱导的糖尿病大鼠给予MEL后,肾脏和肝脏组织的脂质过氧化(TBARS)显著降低。此外,MEL还能抑制肝肾组织抗氧化酶参数超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、还原性谷胱甘肽(GSH)的降低。MEL治疗后肝功能指标(谷丙转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)及肾功能指标(尿素、尿酸、肌酐)均恢复正常。MEL进一步维持了大鼠血脂的正常水平,如甘油三酯、胆固醇、低密度脂蛋白和高密度脂蛋白(LDL, HDL)。从肝、肾细胞的细胞结构判断,肝、肾组织的组织结构得到了修复和恢复。结论:实验诱导的STZ雄性大鼠模型观察到外源性褪黑素对肝肾组织的损伤和损害,表明外源性褪黑素对肝肾组织具有保护作用。
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