Said Eman, Zaitone Sawsan A, Eldosoky Mohamed, Elsherbiny Nehal M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt; Department of Pharmacology & Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
Chem Biol Interact. 2018 Feb 1;281:111-120. doi: 10.1016/j.cbi.2017.12.030. Epub 2017 Dec 30.
Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. Moreover,it is amongst the most common causes of end-stage renal failure. Inflammation is a crucial player in both development and progression of DN. JAK2/STA3 is a pleotropic cascade reported to regulate diverse inflammatory events. Previous studies reported involvement of JAK2/STA3 signal transduction pathway in diabetes-associated renal injury. In the current study, the inhibitory effect of nifuroxazide (25 mg/kg/day, orally) against inflammatory condition associating diabetic kidney progression in rats was evaluated. The underlying hypothesis is mainly via the inhibitory effect of nifuroxazide on STAT3 signaling. Results revealed that nifuroxazide effectively inhibited STAT3 activation in diabetic male rats, improved glomerular filtration function, protected against diabetes-induced histopathological and ultramicroscopic structural alterations. Further, nifuroxazide treatment significantly reduced renal macrophage infiltration and fibrosis and decreased mRNA and protein levels of TNF-α and IL-18 in diabetic renal tissue. The current findings shed the light on nifuroxazide's efficacy as an alternative anti-inflammatory therapy to hinder the development and progression of DN in diabetic patients mainly via STAT3 inhibition.
糖尿病肾病（DN）是糖尿病的一种严重并发症。此外，它是终末期肾衰竭最常见的病因之一。炎症在DN的发生和发展过程中起着关键作用。JAK2/STA3是一种多效性级联反应，据报道可调节多种炎症事件。先前的研究报道JAK2/STA3信号转导通路参与了糖尿病相关的肾损伤。在本研究中，评估了硝呋太尔（25毫克/千克/天，口服）对大鼠糖尿病肾病进展相关炎症状态的抑制作用。潜在的假设主要是基于硝呋太尔对STAT3信号传导的抑制作用。结果显示，硝呋太尔可有效抑制糖尿病雄性大鼠的STAT3激活，改善肾小球滤过功能，预防糖尿病引起的组织病理学和超微结构改变。此外，硝呋太尔治疗显著减少了肾巨噬细胞浸润和纤维化，并降低了糖尿病肾组织中TNF-α和IL-18的mRNA和蛋白水平。目前的研究结果揭示了硝呋太尔作为一种替代性抗炎疗法的疗效，主要通过抑制STAT3来阻碍糖尿病患者DN的发生和发展。
