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-induced 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. Adriamycin produced significant elevation in thiobarbituric acid reactive substances (TBARS), which is an indicator of lipid peroxidation, and significantly inhibited the activity of superoxide dismutase (SOD) in heart and liver tissues, with a significant rise in the serum levels of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase isoenzyme (CK-MB) and lactic dehydrogenase (LDH), indicating acute cardiac 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 significantly reduced the TBARS concentration in both heart and liver and ameliorated the inhibition of cardiac and hepatic SOD activity. In addition, the ACE 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 against adriamycin-induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the limitation of culprit free radicals and the amelioration of oxidative stress.
Abd El-Aziz
M A
MA
Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Othman
A I
AI
Amer
M
M
El-Missiry
M A
MA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004317:Doxorubicin / Q000633:toxicity*; D004656:Enalapril / Q000494:pharmacology*; D005609:Free Radicals; D006321:Heart / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; D005609:Free Radicals; D004656:Enalapril; D004317:Doxorubicin; D002216:Captopril