Studies on curative efficacy of monoterpene eugenol on anti- leukemic drug arsenic trioxide induced cardiotoxicity.

BACKGROUND: Arsenic trioxide (As2 O3 ) is emerging as a frontline agent for the treatment of acute promyelocytic leukemia (APL) but the therapeutic application is limited by its toxicity. QT prolongation, torsades de pointes and sudden cardiac death have been implicated in the As2 O3 therapy. So eugenol is a monoterpene compound is well known for its antioxidant properties and protective effect on the cardiovascular system.

OBJECTIVE: In this study, the cardioprotective effect of eugenol on cardiac electrical conductivity, tissue electrolytes, myocardial markers, antioxidant system, lipid peroxidation and nitric oxide production was investigated in male Wistar rats treated with arsenic trioxide.

RESULTS: The Inductively coupled plasma emission spectroscopic (ICP-OES) analysis pointed out the accumulation of arsenic in heart tissue. The rats administered with arsenic trioxide (4mg/kg body wt) exhibited myocardial damage that was manifested by the elevation of cardiac markers (LDH, CK-MB) enzymes and deterioration in the antioxidant enzymes (GSH, GST, GPx). Combination treatment with eugenol (5mg/kg of body wt) upholds the tissue antioxidant level, Na+ /K+ - ATPase and Ca2+- ATPase activity and brings the cytosolic Ca2+, K+ and Na + levels near to normal value. Conjoined therapy with eugenol ameliorated the membrane peroxidation, restored the normal heart rate and rectified the prolongation of QT interval in the electrocardiogram. Histological examination of cardiac segments also supported the beneficial role of eugenol against arsenic-induced oxidative damages.

CONCLUSION: Our in vivo experimental findings suggest that monoterpenoid eugenol could be a potent and novel cytoprotective agent of clinical application against As2 O3 induced cardiotoxicity.