title: Myocardial toxicity of acute promyelocytic leukaemia drug-arsenic trioxide.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The present study was designed to investigate the toxic mechanism of arsenic in cardiac tissue at its clinically relevant concentrations.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala, India. harinairsbs@gmail.com
authors: V V
authors: VV
authors: Mathews
authors: M V S
authors: MV
authors: Paul
authors: M
authors: M
authors: Abhilash
authors: A
authors: A
authors: Manju
authors: S
authors: S
authors: Abhilash
authors: R H
authors: RH
authors: Nair
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000633:toxicity*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000378:metabolism; D001822:Body Burden; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase; D005982:Glutathione Transferase / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010087:Oxides / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D000077237:Arsenic Trioxide