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.