Kokate Dhananjay, Marathe Padmaja
Department of Pharmacology and Therapeutics, Seth GSMC and KEM Hospital, Acharya Donde Marg, Parel, Mumbai, Maharashtra, India.
Indian J Endocrinol Metab. 2024 Jan-Feb;28(1):47-54. doi: 10.4103/ijem.ijem_414_22. Epub 2024 Feb 26.
Diabetic nephropathy is a progressive condition and a leading cause of end-stage renal disease. Oxidative stress and inflammation play an important role in its pathogenesis. In pre-clinical studies, Montelukast had shown renoprotective and anti-oxidant properties, hence the study was planned to evaluate the effect of Montelukast in a Streptozotocin (STZ) induced model of diabetic nephropathy.
40 Wistar rats of either sex were randomly divided into four groups . 1. Vehicle control group, 2. Enalapril (5 mg/kg), 3. Montelukast low-dose (10 mg/kg) and 4. High-dose (20 mg/kg) group. On day 1, diabetes was induced using a single dose of STZ (60 mg/kg) intraperitoneally. Diabetes induction was verified based on fasting blood glucose (FBG) levels on day 7 and from day 8 to day 42, rats were given study drugs. FBG, serum creatinine, blood urea nitrogen (BUN) and urine microalbumin levels were assessed pre-study and post-study. Assessments of kidney malondialdehyde (MDA), reduced glutathione (GSH) and renal histopathology were carried out at the end of the study.
Montelukast 10 mg/kg group showed significantly lower urine microalbumin levels compared to the vehicle control group (p < 0.05). Montelukast 20 mg/kg group showed significantly lower levels of FBG, serum creatinine, BUN and urine microalbumin compared to the vehicle control group (p < 0.05). In addition, Montelukast 20 mg/kg group also showed better effects on kidney MDA and GSH levels (p < 0.05) and histopathological scores compared to the vehicle control group.
Montelukast showed a protective effect in the model of diabetic nephropathy because of its antioxidant effect.
糖尿病肾病是一种进行性疾病,是终末期肾病的主要原因。氧化应激和炎症在其发病机制中起重要作用。在临床前研究中,孟鲁司特已显示出肾脏保护和抗氧化特性,因此计划开展本研究以评估孟鲁司特在链脲佐菌素(STZ)诱导的糖尿病肾病模型中的作用。
40只Wistar大鼠(雌雄不限)被随机分为四组。1. 赋形剂对照组;2. 依那普利(5毫克/千克)组;3. 孟鲁司特低剂量(10毫克/千克)组;4. 高剂量(20毫克/千克)组。第1天,通过腹腔注射单剂量STZ(60毫克/千克)诱导糖尿病。根据第7天的空腹血糖(FBG)水平验证糖尿病诱导情况,从第8天至第42天,给大鼠服用研究药物。在研究前和研究后评估FBG、血清肌酐、血尿素氮(BUN)和尿微量白蛋白水平。在研究结束时进行肾脏丙二醛(MDA)、还原型谷胱甘肽(GSH)评估和肾脏组织病理学检查。
与赋形剂对照组相比,孟鲁司特10毫克/千克组的尿微量白蛋白水平显著降低(p < 0.05)。与赋形剂对照组相比,孟鲁司特20毫克/千克组的FBG、血清肌酐、BUN和尿微量白蛋白水平显著降低(p < 0.05)。此外,与赋形剂对照组相比,孟鲁司特20毫克/千克组对肾脏MDA和GSH水平(p < 0.05)以及组织病理学评分也显示出更好的效果。
孟鲁司特因其抗氧化作用在糖尿病肾病模型中显示出保护作用。