Oxidative stress induced by the chemotherapeutic agent arsenic trioxide

Arsenic compounds have been used for medicinal purposes throughout history. Arsenic trioxide (As 2 O 3 ) achieved dramatic remissions in patients with acute promyelocytic leukaemia. Unfortunately, the clinical usefulness of As 2 O 3 has been limited by its toxicity. The present study was designed to investigate the toxic effects of As 2 O 3 at its clinical concentrations. Experimental rats were administered with As 2 O 3 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. As 2 O 3 -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 As 2 O 3 treatment. All these toxic effects were found increased with the increase in concentration of As 2 O 3 . The results of the study indicate that As 2 O 3 produced dose-dependant toxic side effects at its clinical concentrations.