European review for medical and pharmacological sciences 2013-02-01

Myocardial toxicity of acute promyelocytic leukaemia drug-arsenic trioxide.

V V Mathews, M V S Paul, M Abhilash, A Manju, S Abhilash, R H Nair

Index: Eur. Rev. Med. Pharmacol. Sci. 17 Suppl 1 , 34-8, (2013)

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Abstract

Arsenic trioxide (As2O3) is an environmental toxicant as well as an effective anti cancer agent against many types of cancers. It is a promising drug for patients with relapsed acute promyelocytic leukaemia (APL), but its clinical efficacy is burdened by the serious cardiac toxicities.The present study was designed to investigate the toxic mechanism of arsenic in cardiac tissue at its clinically relevant concentrations.Experimental rats were administered with As2O3 2, 4 and 8 mg/kg body weight, orally for a period of 45 days. Cardiac toxicities were recorded by lipid peroxidation, activities of glutathione dependent antioxidant and antiperoxidative enzymes, cardiac arsenic accumulation and histopathological changes.In vivo studies revealed a significant rise in lipid peroxidation, decline in reduced glutathione, glutathione dependent antioxidant enzymes and antiperoxidative enzymes in the cardiac tissue of arsenic treated rats. The extent of free radical production was found increased with periodic rise in the arsenic concentration. The experimental group which received 8 mg/kg body weight of arsenic exhibited the highest deposition of arsenic in cardiac tissue. Light microscopic examination of cardiac tissues in arsenic treated rats has showed increased structural abnormalities like myocardial fibre swelling, capillary congestion and micro-haemorrhages.The study concludes that the mechanism of arsenic induced cardiac toxicity is associated with the accumulation of arsenic in tissue and the extent of free radical production.