顺-二氯二氨铂（II）（顺铂，Cis）被广泛用于治疗多种类型的癌症。它有许多重要的毒性副作用，其中最重要的之一是肾毒性。氯丙唑盐酸盐（Clem）作为TRPC5通道最有效的抑制剂，已在Cis引起的肾毒性动物模型中进行了测试。将大鼠分为以下组别：对照组；Cis（8mg / kg）；Cis + 1mg / kg Clem；Cis + 5mg / kg Clem；Cis + 10mg / kg Clem。使用组织病理学和生化分析检测肾脏损伤。通过酶联免疫吸附测定确定尿素氮（UUN），肌酐，尿中中性粒细胞胶体酶相关脂联素（NGAL），血清过氧化氢酶（CAT）和丙二醛（MDA）水平。使用比色法研究总抗氧化状态（TAS）和总氧化状态（TOS）。使用Western blot分析检测nephrin，synaptopodin和Rac家族小GTP酶1（RAC1）表达。发现Cis引起组织病理学改变，包括管型变性，淤血，出血，玻璃样管型，球囊塌陷和凋亡细胞死亡。 Clem 1mg / kg和5mg / kg剂量减轻了组织病理学改变。在Cis施用组中，UUN，肌酐和NGAL水平升高，而所有剂量的Clem降低了这些水平。CAT和TAS水平下降，而TOS和氧化应激指数水平在Cis处理组中升高。 1mg / kg和5mg / kg的Clem剂量对氧化应激具有抗氧化作用。Cis通过增加MDA水平诱导脂质过氧化。所有剂量的Clem降低了MDA水平。Cis降低了nephrin和synaptopodin的表达，而所有剂量的Clem增加了它们的表达。所有剂量的Clem都成功抑制了RAC1表达。Clem通过阻塞TRPC5钙通道，在减少Cis引起的毒性方面具有极佳的改善作用。 ©2023 Wiley Periodicals LLC.

Cis-diamminedichloroplatinum (II) (cisplatin, Cis) is widely employed to treat several types of cancer. It has many important toxic side effects; one of the most important of which is nephrotoxicity. Clemizole hydrochloride (Clem) as the most potent inhibitor of TRPC5 channels was tested in an animal model of Cis-induced nephrotoxicity. Rats were divided into the following groups: control; Cis (8 mg/kg); Cis + 1 mg/kg Clem; Cis + 5 mg/kg Clem; Cis + 10 mg/kg Clem. Kidney injury was detected by histopathological and biochemical analysis. Urine urea nitrogen (UUN), creatinine, urine neutrophil gelatinase-associated lipocalin (NGAL), serum catalase (CAT), and malondialdehyde (MDA) levels were determined by enzyme-linked immunosorbent assay. Total antioxidant status (TAS) and total oxidant status (TOS) were studied using a colorimetric assay. Nephrin, synaptopodin, and Rac family small GTPase 1 (RAC1) expressions were detected by Western blot analysis. Cis was found to induce histopathological alterations, including tubular degeneration, congestion, hemorrhage, hyaline casts, glomerular collapse, and apoptotic cell death. Clem at a dose of 1 and 5 mg/kg attenuated histopathological alterations. UUN, creatinine, and NGAL levels increased in the Cis-administered group, while all doses of Clem decreased in those. CAT and TAS levels decreased, while TOS and oxidative stress index levels increased in the Cis-treated group. A dose of 1 and 5 mg Clem showed antioxidant effects against oxidative stress. Cis induced lipid peroxidation by increasing MDA levels. All doses of Clem reduced MDA levels. Nephrin and synaptopodin expressions were decreased by Cis, and all doses of Clem increased that. All doses of Clem successfully depressed RAC1 expression. Clem showed a highly ameliorating effect on toxicity caused by Cis by blocking TRPC5 calcium channels.© 2023 Wiley Periodicals LLC.