Regional selectivity in ethanol-induced pro-oxidant events within the brain.
Several biochemical parameters that reflect the presence of excess levels of reactive oxygen species were modulated in the brains of rats exposed acutely or subchronically to ethanol. These parameters included depression of cytosolic glutathione (GSH) concentration and of glutamine synthetase levels. However, using these indices, there was a significant difference in susceptibility to ethanol in different brain regions. After dietary exposure to ethanol for 12 days, these indices were selectively depressed in the striatum but not in the cerebral cortex or cerebellum. Eighteen hours after a single acute dose of ethanol (4.5 g/kg body wt), the striatum was also the only one of these areas in which proteolytic activity was elevated by ethanol treatment. Two injections of acetaldehyde (300 mg/kg), given 18 and 2 hr prior to tissue preparation, caused a specific reduction of glutamine synthetase in the striatum and a decrease of GSH levels in both striatum and cerebellum. Taken together, the results suggest a distinctive vulnerability of the striatum to ethanol-promoted oxidative events. Rather than ethanol exerting effects directly, the metabolite acetaldehyde may be the primary agent responsible for these changes.
Department of Community and Environmental Medicine, University of California, Irvine 92715.
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D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005974:Glutamate-Ammonia Ligase / Q000187:drug effects / Q000378:metabolism; D007536:Isomerism; D008297:Male; D010084:Oxidation-Reduction; D010447:Peptide Hydrolases / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000633:toxicity*
D017382:Reactive Oxygen Species; D000431:Ethanol; D010447:Peptide Hydrolases; D005974:Glutamate-Ammonia Ligase