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.