Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
Environ Toxicol Pharmacol. 2008 Jul;26(1):49-55. doi: 10.1016/j.etap.2008.01.006. Epub 2008 Feb 3.
Cisplatin is an effective agent against various solid tumors. However, its nephrotoxicity been reported to be a dose-limiting factor for treating various types of tumors. The aim of this study was to determine the protective effects of ligustrazine on cisplatin-induced nephrotoxicity through tissue oxidant/antioxidant parameters, light microscopic evaluation, and tubular apoptosis in rats. Ligustrazine was administered in doses of 50 and 100mg/kg/day intraperitoneally (i.p.), for 7 consecutive days, starting 2 days before a single intraveneous dose of cisplatin (8mg/kg). Results revealed that treatment with cisplatin alone caused significant changes in the levels of urinary protein, urinary N-acetyl-beta-d-glucosaminidase, serum creatinine, blood urea nitrogen, and kidneys histopathological damages. All the aforementioned changes were effectively attenuated by ligustrazine. In addition, cisplatin caused increases in the levels of malondialdehyde, nitric oxide, nitric oxide synthase and decreases in the levels of reduced glutathione, glutathione-S-transferase, superoxide dismutase. These changes were restored to near normal levels by ligustrazine at 100mg/kg. In conclusion, ligustrazine has dose dependent protective effects against cisplatin-induced renal tubular toxicity.
顺铂是一种有效对抗各种实体瘤的药物。然而，其肾毒性已被报道为治疗各种类型肿瘤的剂量限制因素。本研究旨在通过组织氧化剂/抗氧化剂参数、光镜评估和管状细胞凋亡来确定川芎嗪对顺铂诱导的肾毒性的保护作用。川芎嗪以 50 和 100mg/kg/天的剂量腹腔内（i.p.）给药，连续 7 天，在单次静脉注射顺铂（8mg/kg）前 2 天开始。结果表明，单独使用顺铂会导致尿蛋白、尿 N-乙酰-β-D-氨基葡萄糖苷酶、血清肌酐、血尿素氮和肾脏组织病理学损伤水平的显著变化。川芎嗪可有效减轻所有上述变化。此外，顺铂会导致丙二醛、一氧化氮、一氧化氮合酶水平升高，还原型谷胱甘肽、谷胱甘肽-S-转移酶、超氧化物歧化酶水平降低。这些变化在 100mg/kg 时可通过川芎嗪恢复到接近正常水平。总之，川芎嗪对顺铂诱导的肾小管毒性具有剂量依赖性的保护作用。
