Protective effect of captopril against cisplatin-induced nephrotoxicity in rats.
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 (7.5 mg/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 (60 mg/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.
El-Sayed
El-Sayed M
el-SM
Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Nasr-City, Cairo, Egypt. elsayed200_1956@yahoo.com
Abd-Ellah
Mohamed F
MF
Attia
Sabry M
SM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents; D001806:Blood Urea Nitrogen; D002216:Captopril / Q000494:pharmacology*; D002945:Cisplatin; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D000970:Antineoplastic Agents; D019332:Endothelin-1; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D002216:Captopril; D003404:Creatinine; D005978:Glutathione; D002945:Cisplatin