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

Abstract

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.

Prevention of High-Dose Chemotherapy–Induced Cardiotoxicity in High-Risk Patients by Angiotensin-Converting Enzyme Inhibition

“…In several studies, both sulfydryland non-sulfydryl-containing ACEIs have been shown to be effective free radical scavengers, having an antioxidant effect on adriamycin-induced cardiotoxicity. 18,33 The mechanism by which enalapril prevents the development of cardiotoxicity remains uncertain. Hemodynamic abnormalities and systemic activation of RAS probably were not present in our population, given the normal LVEF observed at the time of patient randomization.…”

“…9 -12 Furthermore, data referring to experimental models suggest that the cardiac renin-angiotensin system (RAS) plays an important role in the development of anthracycline-induced cardiomyopathy and that treatment with ACEIs protects against chemotherapy-induced cardiotoxicity. [13][14][15][16][17][18][19] Hence, it is likely that a prophylactic strategy based on the use of ACEIs in selected high-risk patients could prevent cardiotoxicity.…”

Can short-term fasting protect against doxorubicin-induced cardiotoxicity?

“…Furthermore, the treatment significantly affected the proteome lysine acetylation status in the heart, inducing deacetylation (Figure 1), although the significance of this observation is currently unknown. Because previously published studies have reported that acute Dox treatment does affect many of these variables and processes [8][9][10][11][35][36][37] , we believe that complete fasting of the animals in our study may have exerted an unintended cardioprotective effect against the Dox-induced insult. However, further investigation is required to confirm our interpretation of the data.…”

Protective effect of Moringa peregrina seed oil against doxorubicin-induced hepatotoxicity in male mice

“…Inflammation is a major component in the pathogenesis of DOX toxicity that is orchestrated in part by endogenous and migrating leukocytes. Abd El-Aziz et al (2001) demonstrated that a 15 mg/kg single injection of DOX caused increased lipid peroxidation and produced reactive oxygen species in liver tissue, thus reduced the antioxidant defence mechanism. Dilatation of the blood sinusoids and degeneration may be due to this stress.…”