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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #247161

Title: N-3 Polyunsaturated Fatty Acids are Selective Targets of Ethanol Withdrawal-Induced Lipid Peroxidation

item LONG, ERIC - University Of North Dakota
item ROSENBERGER, THAD - University Of North Dakota
item Picklo, Matthew

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/15/2009
Publication Date: 12/4/2009
Citation: Long, E.K., Rosenberger, T.A., Picklo, M.J. 2009. N-3 Polyunsaturated Fatty Acids are Selective Targets of Ethanol Withdrawal-Induced Lipid Peroxidation. Meeting Abstract. Poster No. 290.

Interpretive Summary:

Technical Abstract: Ethanol withdrawal is a potentially life-threatening neurological syndrome owing to decreased GABA transmission and increased glutamatergic transmission resulting in a pro-excitotoxic state. Previous data indicate that ethanol withdrawal may increase CNS lipid peroxidation particularly to the n-3 fatty acid, docosahexaenoate (DHA; 22:6; n-3). In order to further define the role of oxidative damage in ethanol withdrawal, we monitored levels glutathione adducts of 4-hydroxy-2-hexenal (GSHHE) and glutathione adducts of 4-hydroxy-2-nonenal (GSHNE) as biomarkers of lipid peroxidation of n-3 and n-6 PUFA in brain, respectively, using a highly-sensitive isotope dilution LC-MS/MS assay for GSHHE and GSHNE we developed. Male, Sprague-Dawley rats received an ethanol containing diet for six weeks followed by withdrawal for 0 to 7 days before killing and removal and dissection of the brain. Our results show that GSHHE content was significantly elevated (300%) in the cerebral cortex following 2 days of withdrawal with return to control values by 7 days post withdrawal. GSHNE content was unchanged in all brain regions (cortex, hippocampus, cerebellum) tested. Under control or ethanol conditions, levels of GSHHE were significantly greater (2-20-fold) than levels of GSHNE in these regions. In vitro, enzymatic experiments demonstrated no difference in the rate of formation of GSHHE or GSHNE adducts as a result of ethanol intoxication or withdrawal. However, the rate of formation of GSHHE adducts was significantly higher (~50%) than the formation of GSHNE adducts under all conditions and regions. Subsequent metabolism of GSHHE or GSHNE was not observed. Our results indicate that GSHHE adducts are a sensitive marker of oxidative damage to DHA in the brain as a result of ethanol withdrawal, that 4-hydroxy-hexenal is metabolized to the GSH adduct more efficiently than HNE, and support the findings that DHA is a selective target of oxidative damage in the brain. The extent to which pharmacologic therapy for withdrawal (e.g. benzodiazepines) inhibits ethanol withdrawal-induced lipid peroxidation is not known but needs more study.