Ahamad Rizwan, Bhandari Uma, Nabi Sayima, Sharma Shweta
Department of Pharmacology, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi-110062, India.
Iran J Basic Med Sci. 2024;27(11):1447-1455. doi: 10.22038/ijbms.2024.78221.16908.
Nephropathy is the most common comorbidity linked to T2D. The present study aimed to examine the potential of saroglitazar in the context of a high-fat diet and low-dose streptozotocin-induced diabetic nephropathy in Wistar rats.
Molecular docking simulation investigations were conducted on the ligand-binding region of type IV collagen and Kidney injury molecule-1 (KIM-1), using saroglitazar and fenofibrate as the subjects. The rats were fed either a conventional rodent diet or a high-fat diet for two weeks. Following a two-week period, the rats given an HFD were administered with a low-dose of STZ (35 mg/kg, IP). Rats with experimentally induced diabetes were categorized into five groups: normal control; diabetic control; HFD+STZ+saroglitazar (2 mg/kg); HFD+STZ+saroglitazar (4 mg/kg); HFD+STZ+fenofibrate (100 mg/kg) treated orally for 21 days with continuation on HFD. After 21 days, rats were kept on fasting overnight, blood and urine was acquired for various biochemical analysis. Animals were sacrificed, and kidney tissues were removed for histopathological studies.
investigation showed a substantial affinity between saroglitazar and fenofibrate with KIM-1 and type IV collagen. Saroglitazar produced a significant (<0.01) reduction in weight of the body, serum blood sugar, albumin, creatinine, and BUN levels. Further, saroglitazar significantly (<0.01) reduced the KIM-1 and type IV collagen levels in the urine of diabetic rats. Histopathological results showed improvement in tubular degeneration, necrosis, and dilatation of Bowman's space in kidney tissue.
Saroglitazar attenuated renal injury by improving renal function in HFD+STZ-induced DN in Wistar rats.
肾病是与2型糖尿病相关的最常见合并症。本研究旨在探讨在高脂饮食和低剂量链脲佐菌素诱导的Wistar大鼠糖尿病肾病背景下，沙罗格列扎的作用潜力。
以沙罗格列扎和非诺贝特为研究对象，对IV型胶原和肾损伤分子-1（KIM-1）的配体结合区域进行分子对接模拟研究。大鼠喂养常规啮齿动物饲料或高脂饮食两周。两周后，给予高脂饮食的大鼠腹腔注射低剂量链脲佐菌素（35 mg/kg）。将实验性诱导糖尿病的大鼠分为五组：正常对照组；糖尿病对照组；高脂饮食+链脲佐菌素+沙罗格列扎（2 mg/kg）；高脂饮食+链脲佐菌素+沙罗格列扎（4 mg/kg）；高脂饮食+链脲佐菌素+非诺贝特（100 mg/kg），口服给药21天，并继续给予高脂饮食。21天后，大鼠隔夜禁食，采集血液和尿液进行各种生化分析。处死动物，取出肾脏组织进行组织病理学研究。
研究表明，沙罗格列扎和非诺贝特与KIM-1和IV型胶原之间具有显著亲和力。沙罗格列扎使体重、血清血糖、白蛋白、肌酐和尿素氮水平显著降低（<0.01）。此外，沙罗格列扎显著降低（<0.01）糖尿病大鼠尿液中的KIM-1和IV型胶原水平。组织病理学结果显示，肾脏组织的肾小管变性、坏死和鲍曼间隙扩张有所改善。
在高脂饮食+链脲佐菌素诱导的Wistar大鼠糖尿病肾病中，沙罗格列扎通过改善肾功能减轻了肾损伤。
