Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Taibah University, Madinah, Saudi Arabia.
Eur J Pharmacol. 2011 Oct 1;668(1-2):278-84. doi: 10.1016/j.ejphar.2011.06.051. Epub 2011 Jul 13.
Cisplatin is chemotherapeutic drug used in treatment of malignancies. However, its clinical utility is limited by nephrotoxicity. The purpose of present study is to investigate biochemical and molecular effects of alpha lipoic acid (ALA) to protect against cisplatin-induced nephrotoxicity in mice. Cisplatin (12 mg/kg/day) was administered i.p. for 4 days. Group of mice were given ALA (20 mg/kg/day) for 18 days. Another set were administered ALA for 4 days before and 14 days after cisplatin intoxication. The results obtained revealed that kidney/body weight ratio of cisplatin-treated mice was increased by +40%. ALA intake declined the ratio by -19%. Serum creatinine and urea levels were increased in cisplatin-treated mice by +375% and +69%, respectively. These changes were moved to normalcy upon ALA intake. Cisplatin treatment elevated malondialdehyde (MDA) by 27 fold and declined reduced glutathione (GSH) by -49%. Cisplatin decreased catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes by -47%, -49% and -59%, respectively. ALA decreased the MDA by -286% and increased the GSH, catalase, SOD and GPx levels by +60%, +81%, +90% and +38%, respectively. ALA increased mRNA expression of catalase, CuZn SOD and GPx genes near to normalcy compared to cisplatin-treated mice. Cisplatin-treated mice increased caspase-3-activity by +223%, nitric oxide (NO) by +74% and inducible nitric oxide synthase (iNOS) by 10 fold. ALA intake declined these changes by -43%, -45% and -73%, respectively. ALA may play renoprotective role on cisplatin-induced nephrotoxicity through antioxidant and antiapoptotic mechanisms combined with initiation of mRNA expression of antioxidant genes.
顺铂是一种用于治疗恶性肿瘤的化疗药物。然而，其临床应用受到肾毒性的限制。本研究旨在探讨α-硫辛酸（ALA）对预防顺铂诱导的小鼠肾毒性的生化和分子作用。顺铂（12mg/kg/天）腹腔注射给药 4 天。一组小鼠给予 ALA（20mg/kg/天）18 天。另一组在顺铂中毒前 4 天和后 14 天给予 ALA。结果表明，顺铂处理组小鼠的肾/体重比增加了+40%。ALA 摄入使该比值降低了-19%。顺铂处理组小鼠的血清肌酐和尿素水平分别升高了+375%和+69%。ALA 摄入使这些变化恢复正常。顺铂处理使丙二醛（MDA）增加了 27 倍，使还原型谷胱甘肽（GSH）降低了-49%。顺铂使过氧化氢酶、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）的活性分别降低了-47%、-49%和-59%。ALA 使 MDA 降低了-286%，使 GSH、过氧化氢酶、SOD 和 GPx 的水平分别增加了+60%、+81%、+90%和+38%。与顺铂处理组小鼠相比，ALA 使过氧化氢酶、CuZn SOD 和 GPx 基因的 mRNA 表达增加接近正常。顺铂处理组小鼠的 caspase-3 活性增加了+223%，一氧化氮（NO）增加了+74%，诱导型一氧化氮合酶（iNOS）增加了 10 倍。ALA 摄入使这些变化分别降低了-43%、-45%和-73%。ALA 通过抗氧化和抗凋亡机制以及启动抗氧化基因的 mRNA 表达，可能对顺铂诱导的肾毒性发挥肾保护作用。
