Objective: The present study was designed to investigate the chemoprotective efficacy of an L-cysteine-based oxovanadium (IV) complex, namely, oxovanadium (IV)-L-cysteine methyl ester complex (VC-IV) against cisplatin (CDDP)-induced renal injury in Swiss albino mice.

Methods: CDDP was administered intraperitoneally (5 mg/kg body weight) and VC-IV was administered orally (1 mg/kg body weight) in concomitant and 7 days pre-treatment schedule.

Results: CDDP-treated mice showed marked kidney damage and renal failure. Administration of VC-IV caused significant attenuation of renal oxidative stress and elevation of antioxidant status. VC-IV also significantly decreased serum levels of creatinine and blood urea nitrogen, and improved histopathological lesions. Western blot analysis of the kidneys showed that VC-IV treatment resulted in nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) through modulation of cytosolic Kelch-like ECH-associated protein 1. Thus, VC-IV stimulated Nrf2-mediated activation of antioxidant response element (ARE) pathway and promoted expression of ARE-driven cytoprotective proteins, heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1, and enhanced activity of antioxidant enzymes. Interestingly, VC-IV did not alter the bioavailability and renal accumulation of CDDP in mice.

Discussion: In this study, VC-IV exhibited strong nephroprotective efficacy by restoring antioxidant defense mechanisms and hence may serve as a promising chemoprotectant in cancer chemotherapy.

目的：本研究旨在研究基于L-半胱氨酸的氧钒（IV）复合物，即氧钒（IV）-L-半胱氨酸甲酯复合物（VC-IV）对顺铂（CDDP）诱导的化学保护作用。瑞士白化病小鼠的肾脏损伤。

方法：腹膜内给予CDDP（5 mg / kg体重），VC-IV口服给予（1 mg / kg体重），并同时进行7天的治疗。

结果：CDDP处理的小鼠显示出明显的肾脏损害和肾功能衰竭。VC-IV的使用显着减轻了肾脏的氧化应激并提高了抗氧化剂的状态。VC-IV还可以显着降低血清肌酐和血液尿素氮水平，并改善组织病理学病变。肾脏的Western印迹分析表明，VC-IV处理通过调节胞质Kelch样ECH相关蛋白1导致核因子E2相关因子2（Nrf2）的核易位。因此，VC-IV刺激了Nrf2介导的活化抗氧化反应元件（ARE）途径的表达，并促进了ARE驱动的细胞保护蛋白，血红素加氧酶1和NAD（P）H：醌氧化还原酶1的表达，并增强了抗氧化酶的活性。有趣的是，

讨论：在这项研究中，VC-IV通过恢复抗氧化防御机制表现出强大的肾脏保护功效，因此可能在癌症化疗中作为有希望的化学保护剂。