Motawi Tarek K, Ahmed Samia A, A Hamed Manal, El-Maraghy Shohda A, M Aziz Wessam
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Therapeutic Chemistry Department, National Research Centre, Dokki, Cairo, Egypt.
J Biomed Res. 2019 Apr 22;33(2):113-121. doi: 10.7555/JBR.31.20160028.
The study aimed to explore the prophylactic effect of melatonin, rowatinex; a naturally occurring renal drug, and its combination on diabetic nephropathy in type 2 diabetic rats. Diabetes was induced by intraperitoneal injection of a single dose of streptozotocin (50 mg/g body weight). Three days before diabetes induction, rats were daily treated with melatonin, rowatinex and their combination continuously for 8 weeks. Evaluation was done through measuring blood urea nitrogen (BUN), serum uric acid, serum creatinine, urine creatinine, creatinine clearance, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), total antioxidant capacity (TAC), kidney injury molecule-1 (KIM-1), heat shock protein-70 (HSP-70), caspase-3, transforming growth factor β1 (TGFβ1), DNA degradation by the comet assay and total protein contents. Histopathologic study was also done for the kidney and the pancreas. Drastic changes in all measured parameters of the diabetic rats were observed. Treatment with melatonin and rowatinex showed amelioration to variable degrees. In conclusion, melatonin showed the most potent effect on protecting rats from deleterious action of diabetic nephropathy followed by its combination with rowatinex.
该研究旨在探讨褪黑素(一种天然存在的肾脏药物)、罗瓦替丁及其组合对2型糖尿病大鼠糖尿病肾病的预防作用。通过腹腔注射单剂量链脲佐菌素(50 mg/g体重)诱导糖尿病。在诱导糖尿病前三天,大鼠每天连续接受褪黑素、罗瓦替丁及其组合治疗8周。通过测量血尿素氮(BUN)、血清尿酸、血清肌酐、尿肌酐、肌酐清除率、一氧化氮(NO)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、总抗氧化能力(TAC)、肾损伤分子-1(KIM-1)、热休克蛋白-70(HSP-70)、半胱天冬酶-3、转化生长因子β1(TGFβ1)、彗星试验检测DNA降解以及总蛋白含量进行评估。还对肾脏和胰腺进行了组织病理学研究。观察到糖尿病大鼠所有测量参数都发生了剧烈变化。褪黑素和罗瓦替丁治疗均显示出不同程度的改善。总之,褪黑素对保护大鼠免受糖尿病肾病的有害作用效果最为显著,其次是其与罗瓦替丁的组合。