Oxidative stress induced by the chemotherapeutic agent arsenic trioxide

Arsenic compounds have been used for medicinal purposes throughout history. Arsenic trioxide (As₂O₃) achieved dramatic remissions in patients with acute promyelocytic leukaemia. Unfortunately, the clinical usefulness of As₂O₃ has been limited by its toxicity. The present study was designed to investigate the toxic effects of As₂O₃ at its clinical concentrations. Experimental rats were administered with As₂O₃ 2, 4 and 8 mg/kg body weight for a period of 45 days and the serum glucose, creatine kinase, lactate dehydrogenase, lipid peroxidation and antioxidant status were measured. As₂O₃-treated rats showed elevated serum glucose, creatine kinase and lactate dehydrogenase concentrations. Lipid peroxidation product malondialdehyde was found to be produced more in arsenic-treated rats. Reduced glutathione and glutathione-dependant antioxidant enzymes, glutathione-S-transferase and glutathione peroxidase, and the antiperoxidative enzymes, superoxide dismutase and catalase, concentrations were reduced with the As₂O₃ treatment. All these toxic effects were found increased with the increase in concentration of As₂O₃. The results of the study indicate that As₂O₃ produced dose-dependant toxic side effects at its clinical concentrations.