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 between 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, the increased accumulation of copper, increased production of malondialdehyde (MDA), increased activity of glutathione peroxidase along with alterations in glutathione and glutathione disulfide concentrations was indicative of oxidative stress. The production of MDA was directly related to the level of copper in both areas of the brain indicating that excess copper may be the primary cause of DS neurotoxicity.
Delmaestro
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College of Pharmacy and Allied Health Professions, Toxicology Program, St. John's University, Jamaica, NY.
Trombetta
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LD
D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D004221:Disulfiram / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D008054:Lipid Peroxides; D008315:Malondialdehyde; D003300:Copper; D005979:Glutathione Peroxidase; D005978:Glutathione; D004221:Disulfiram