THE EFFECTS OF DISULFIRAM ON THE HIPPOCAMPUS AND CEREBELLUM OF THE RAT-BRAIN - A STUDY ON OXIDATIVE STRESS

The purpose of this investigation was to study the relationship betwee n disulfiram (DS) toxicity, lipid peroxidation, and copper in order to further elucidate the mechanisms of DS toxicity. Male Sprague-Dawley rats were dosed with either 375, 750 or 1500 mg/kg disulfiram via oral intubation for 1, 3 and 6 weeks. In the hippocampus and cerebellum, t he increased accumulation of copper, increased production of malondial dehyde (MDA), increased activity of glutathione peroxidase along with alterations in glutathione and glutathione disulfide concentrations wa s indicative of oxidative stress. The production of MDA was directly r elated to the level of copper in both areas of the brain indicating th at excess copper may be the primary cause of DS neurotoxicity.