Potential protective role of angiotensin-converting enzyme inhibitors captopril and enalapril against adriamycin-induced acute cardiac and hepatic toxicity in rats

Captopril and enalapril-angiotensin-converting enzyme (ACE) inhibitors-were evaluated for their antioxidative protective action against adriamycin-ind uced cardiac and hepatic toxicity. Rats were treated with either captopril (10 mg kg(-1)) or enalapril (2 mg kg(-1)) intragastrically (i.g.) daily for 7 days before single intraperitoneal (i.p.) injection with adriamycin (15 mg kg(-1)). The animals were killed 30 h after adriamycin administration. A driamycin produced significant elevation in thiobarbituric acid reactive su bstances (TBARS), which is an indicator of lipid peroxidation, and signific antly inhibited the activity of superoxide dismutase (SOD) in heart and liv er tissues, with a significant rise in the serum levels of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kina se isoenzyme (CK-MB) and lactic dehydrogenase (LDH), indicating acute cardi ac toxicity. A single injection of adriamycin did not affect the cardiac or hepatic glutathione (GSH) content or cardiac catalase (CAT) activity, but hepatic CAT activity was elevated. Pretreatment with ACE inhibitors signifi cantly reduced the TBARS concentration in both heart and fiver and ameliora ted the inhibition of cardiac and hepatic SOD activity. In addition, the AC E inhibitors significantly improved the serum levels of GOT, GPT, CK-MB and LDH in adriamycin-treated rats. Thus, these results suggest that captopril and enalapril possess antioxidative potential that may protect the heart a gainst adriamycin-induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the limitation of culprit free radi cals and the amelioration of oxidative stress. Copyright (C) 2001 John Wile y & Sons, Ltd.