Adaramoye Oluwatosin, Akanni Olubukola, Adesanoye Omoloa, Labo-Popoola Owoola, Olaremi Olabanji
Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan.
Niger J Physiol Sci. 2012 Dec 18;27(2):137-44.
Metformin hydrochloride (MET) and glibenclamide (GB) are used in the management of Type 2 Diabetes (T2D). This study was designed to investigate the toxic effect of MET and GB in the Liver, kidney and testis of rats. Twenty one rats were divided into three groups of seven rats each; group 1 served as control, groups 2 and 3 received GB and MET at doses of 5 and 30 mg/kg, respectively, for 21 days by oral gavage. Results indicate that MET and GB treatment did not affect body weight-gain in the rats. Also, there were no treatment-related changes in the absolute and relative weights of liver, kidney, and testis in MET and GB-treated rats relative to controls. However, significant increase (p<0.05) in testicular lipid peroxidation levels were accompanied by reduction in epididymal sperm count and motility in MET and GB-treated rats, whereas sperm live/dead ratio was unaffected. Specifically, MET and GB decreased sperm count and motility by 34%, 31% and 25%, 28%, respectively. Activities of hepatic and renal superoxide dismutase (SOD) and catalase (CAT), serum alkaline phosphatase, lactate dehydrogenase and alanine aminotransferase were not significantly (p>0.05) affected in MET and GB-treated rats, whereas testicular SOD, CAT, glutathione, serum aspartate aminotransferase and conjugated bilirubin were markedly affected by MET treatment. Histopathological results showed marked necrosis, degeneration of seminiferous tubules and defoliation of spermatocytes in testis of MET-treated rats. Taken together, MET and GB induced lipid peroxidation, affected seminal qualities and decreased antioxidant status. These drugs may interfere with normal biochemical processes in testis and liver of the rats.
盐酸二甲双胍（MET）和格列本脲（GB）用于2型糖尿病（T2D）的治疗。本研究旨在调查MET和GB对大鼠肝脏、肾脏和睾丸的毒性作用。将21只大鼠分为三组，每组7只；第1组作为对照组，第2组和第3组分别以5 mg/kg和30 mg/kg的剂量经口灌胃给予GB和MET，持续21天。结果表明，MET和GB治疗不影响大鼠体重增加。此外，与对照组相比，MET和GB治疗组大鼠肝脏、肾脏和睾丸的绝对重量和相对重量没有与治疗相关的变化。然而，MET和GB治疗组大鼠睾丸脂质过氧化水平显著升高（p<0.05），同时附睾精子数量和活力降低，而精子活/死比率未受影响。具体而言，MET和GB分别使精子数量和活力降低了34%、31%和25%、28%。MET和GB治疗组大鼠肝脏和肾脏超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性、血清碱性磷酸酶、乳酸脱氢酶和谷丙转氨酶没有受到显著影响（p>0.05），而MET治疗显著影响了睾丸SOD、CAT、谷胱甘肽、血清谷草转氨酶和结合胆红素。组织病理学结果显示，MET治疗组大鼠睾丸出现明显坏死、生精小管变性和精母细胞脱落。综上所述，MET和GB诱导脂质过氧化，影响精液质量并降低抗氧化状态。这些药物可能干扰大鼠睾丸和肝脏的正常生化过程。
