Production of reactive oxygen species following acute ethanol or acetaldehyde and its reduction by acamprosate in chronically alcoholized rats

The salicylate trap method, combined with microdialysis, has been used to validate whether reactive oxygen species, particularly hydroxyl radicals, ((OH)-O-center dot), are generated in the hippocampus of male Wistar rats after acute intraperitoneal administration of either ethanol, 2 and 3 g/kg, or acetaldehyde, 200 mg, or during the initial stages of ethanol withdrawal after chronic ethanol intoxication. Salicylate (5 MM) was infused into the hippocampus via the microdialysis probe and the products of its metabolism by hydroxyl radical, particularly 2,3-dihydroxybenzoic acid (2,3-DHBA) as well as 2,5-dihydroxybenzoic acid (2,5-DHBA) assayed by HPLC (High Pressure Liquid Chromatography). Acetaldehyde, 200 mg/kg, and the higher acute dose of ethanol, 3 g/kg, induced transitory increases in 2,3-DHBA and 2,5-DHBA microdialysate content. At the cessation of four weeks of chronic ethanol intoxication, (by the vapour inhalation method), the mean blood alcohol level was 1.90 g/l. Significant increases of microdialysate 2,3-DHBA and 2,5-DHBA levels were assayed 3 h after alcohol withdrawal which were sustained for a further 5 and I h 40 min respectively. Oral administration of Acamprosate, 400 mg/kg/day, during the chronic ethanol intoxication procedure prevented the increased formation of 2,3- and 2,5-DHBA by comparison to rats chronically ethanol intoxicated alone. (c) 2005 Elsevier B.V All rights reserved.