Mansour Mahmoud A, Al-Shabanah Othman A, El-Khashef Hassan A
Department of Pharmacology, College of Pharmacy, King Saud University, P.O Box 2457, Riyadh 11451, Saudi Arabia.
J Biochem Mol Biol. 2003 Jul 31;36(4):373-8. doi: 10.5483/bmbrep.2003.36.4.373.
Effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on the renal dysfunction that is induced by cisplatin (CDDP) were investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced renotoxicity, which was manifested by increasing the sensitivity of isolated urinary bladder rings to acetylcholine (ACh), together with a significant elevation of serum urea and creatinine, and a severe decrease in serum albumin. Moreover, renal dysfunction was further confirmed by a significant decrease of enzyme activities, such as glutathione peroxidase, GSH-Px (E.C 1.11.1.9), catalase (E.C 1.11.1.6), as well as a significant increase in lipid peroxides that were measured as malondialdhyde (MDA) in kidney tissue homogenates. The administration of L-arginine (70 mg/kg/d p.o in drinking water 5 d before and 5 d after the CDDP injection) significantly ameliorated the renotoxic effects of CDDP, as judged by restoring the normal responses of isolated bladder rings to Ach, and also by an improvement in a range of renal function indices, which included serum urea and creatinine concentrations and kidney weight. In addition, L-arginine prevents the rise of MDA, as well as a reduction of GSH-Px and catalase activities in kidney tissues homogenates. On the other hand, the administration of L-NAME (4 mg/kg/d p.o) resulted in no protection against renal dysfunction that was induced by CDDP treatment. The findings of this study suggest that L-arginine can attenuate kidney injury that is produced by CDDP treatment. In addition, L-arginine may be a beneficial remedy for CDDP-induced renal toxicity, and could be used to improve the therapeutic index of CDDP.
研究了L-精氨酸和NG-硝基-L-精氨酸甲酯（L-NAME）对顺铂（CDDP）诱导的肾功能障碍的影响。单次腹腔注射CDDP（7.5mg/kg）可诱导肾毒性，表现为离体膀胱环对乙酰胆碱（ACh）的敏感性增加，同时血清尿素和肌酐显著升高，血清白蛋白严重降低。此外，通过测定肾组织匀浆中谷胱甘肽过氧化物酶（GSH-Px，E.C 1.11.1.9）、过氧化氢酶（E.C 1.11.1.6）等酶活性的显著降低以及脂质过氧化物（以丙二醛，MDA衡量）的显著增加，进一步证实了肾功能障碍。在CDDP注射前5天和注射后5天，通过饮水给予L-精氨酸（70mg/kg/d），根据离体膀胱环对乙酰胆碱恢复正常反应以及一系列肾功能指标（包括血清尿素和肌酐浓度以及肾脏重量）的改善情况判断，L-精氨酸显著改善了CDDP的肾毒性作用。此外，L-精氨酸可防止肾组织匀浆中MDA的升高以及GSH-Px和过氧化氢酶活性的降低。另一方面，给予L-NAME（4mg/kg/d）未能对CDDP治疗诱导的肾功能障碍起到保护作用。本研究结果表明，L-精氨酸可减轻CDDP治疗所致的肾损伤。此外，L-精氨酸可能是治疗CDDP诱导的肾毒性的有益药物，可用于提高CDDP的治疗指数。
