Protective effect of captopril against cisplatin induced nephrotoxicity in rats

ABSTRACT

This study has been initiated to determine whether captopril, an angiotensin-converting enzyme [ACE] inhibitor containing sulfhydryl [-SH] group can protect against cisplatin-induced nephrotoxicity in rats. A single dose of cisplatin [7.5mg/kg bwt] injected i.p. caused a significant increase in blood urea nitrogen [BUN] and creatinine levels amounting to 402% and 573%, respectively with a marked elevation in lipid peroxides measured as malondialdehyde [MDA] content [54%], accompanied by a significant decrease in reduced glutathione [GSH] content [27%] of kidney tissue as compared to control group. In addition, there were marked increases in kidney tissue content of nitric oxide [NO] [43%] and plasma endothelin-1[ET-1] [37%]. On the other hand, administration of captopril [60mg/kg bwt, i.p.] 1 h before cisplatin protected the kidney as indicated by restoration of BUN, creatinine, MDA, GSH, NO and ET-1. These results indicate that captopril, an ACEI, has a protective effect against cisplatin-induced damage to kidney. This reflects the beneficial role of captopril in treatment of renovascular hypertention and congestive heart failure; an effect that may be related to its free radicals scavenging and antioxidant effects which are sulfhydryl dependent