Department of Anatomy and Cell Biology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Anatomy and Cell Biology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Toxicology. 2020 Nov;444:152583. doi: 10.1016/j.tox.2020.152583. Epub 2020 Sep 8.
Extracellular matrix (ECM) exerts a major role in maintaining the structure and developmental processes of tissues. To form the tubular basement membrane in the kidney, sulfate proteoglycans, collagen, laminin, fibronectin, and other glycoproteins congregate in the ECM. As an insecticide, diazinon (DZN) may alter the proportion of ECM by cholinesterase activity inhibition and oxidative stress. The naturally, alpha-lipoic acid (ALA) plays an effective and therapeutic role in the treatment of toxicities and diseases in the body. In the current study, an attempt was made to evaluate the impacts of alpha-lipoic acid on the distribution of fibronectin and laminin in the renal tubules of male Wistar rats following exposure to diazinon. In this study, the animal groups comprised 30 adult male Wistar rats (almost three months old) randomly distributed into the following groups; control, DZN (40 mg/kg), DZN + ALA (40 mg/kg+100 mg/kg), ALA (100 mg/kg), and sham. The rats were anesthetized after six weeks. Blood sampling was performed, and kidneys were removed for immunohistochemistry study. Diazinon reduced the distribution of fibronectin and laminin and significantly inhibited cholinesterase activity in the renal tubules. Furthermore, urea and creatinine levels were higher in diazinon than in other groups. ALA in the co-treatment group enhanced cholinesterase activity and distribution of both glycoproteins in the renal tubules. Urea and creatinine levels were meaningfully diminished in the DZN + ALA group. The nephrotoxic effect of diazinon in vivo was the reduced distribution of laminin and fibronectin, probably induced by cholinesterase activity inhibition. As an antioxidant with specific properties, ALA reduces the nephrotoxic effects of diazinon by multifarious mechanisms.
细胞外基质 (ECM) 在维持组织的结构和发育过程中起着重要作用。硫酸乙酰肝素蛋白聚糖、胶原蛋白、层粘连蛋白、纤维连接蛋白和其他糖蛋白在 ECM 中聚集,以形成肾脏的管状基底膜。敌敌畏(DZN)作为一种杀虫剂,可能通过抑制胆碱酯酶活性和氧化应激来改变 ECM 的比例。天然的α-硫辛酸 (ALA) 在治疗体内毒性和疾病方面发挥着有效和治疗作用。在本研究中,尝试评估α-硫辛酸对暴露于敌敌畏后的雄性 Wistar 大鼠肾脏小管中纤维连接蛋白和层粘连蛋白分布的影响。在这项研究中,将 30 只成年雄性 Wistar 大鼠(大约三个月大)随机分为以下几组:对照组、DZN(40mg/kg)、DZN+ALA(40mg/kg+100mg/kg)、ALA(100mg/kg)和假手术组。六周后,大鼠被麻醉。进行血液取样,并取出肾脏进行免疫组织化学研究。敌敌畏降低了纤维连接蛋白和层粘连蛋白的分布,并显著抑制了肾小管中的胆碱酯酶活性。此外,尿素和肌酐水平在敌敌畏组中高于其他组。在联合治疗组中,ALA 增强了肾小管中两种糖蛋白的胆碱酯酶活性和分布。DZN+ALA 组的尿素和肌酐水平显著降低。敌敌畏在体内的肾毒性作用是层粘连蛋白和纤维连接蛋白分布减少,可能是由胆碱酯酶活性抑制引起的。作为一种具有特定性质的抗氧化剂,ALA 通过多种机制减轻敌敌畏的肾毒性作用。