linoleic-acid and Substance-Withdrawal-Syndrome

Essential fatty acids (EFAs) are major structural components of the brain and through their effects on membrane properties can influence nerve conduction, transmitter release, and transmitter action. Prostaglandins (PGs) derived from EFAs have profound behavioral effects and are also able to modify conduction and transmitter function. Effects of alcohol on EFAs and PGs are therefore good candidates for explaining at least some of the actions of alcohol on brain function. Ethanol has three main known actions on EFA and PG metabolism: it reduces blood linoleic acid levels and induces or exaggerates EFA deficiency states; it blocks metabolism of linoleic acid to EFA metabolites which are known to be important in brain structure; and it enhances conversion of the linoleic acid metabolite, dihomo-gamma-linolenic acid, to PGE1. This review demonstrates that some of the short-term behavioral effects of ethanol and some of its long-term adverse effects on brain, liver, and other tissues may be partly explicable in terms of ethanol actions on EFA and PG metabolism. Modification of such metabolism by dietary and other means has already been shown to influence the effects of alcohol and alcohol withdrawal in both humans and animals. This promises to be a fruitful source of investigation with substantial implications for the understanding and treatment of alcoholism.

Topics: Alcoholism; Alprostadil; Animals; Drug Interactions; Ethanol; Fatty Acids, Essential; Fatty Acids, Unsaturated; Fatty Liver, Alcoholic; Female; gamma-Linolenic Acid; Guinea Pigs; Humans; Linoleic Acid; Linoleic Acids; Linolenic Acids; Lithium; Male; Mice; Oenothera biennis; Plant Oils; Prostaglandins; Rats; Research; Substance Withdrawal Syndrome

The identification of the main dieneconjugated "free-radical marker" in human serum led to a study of free-radical activity in chronic alcoholics. 66 patients were investigated immediately after alcohol withdrawal and over 1-4 weeks' follow-up. The control groups were 76 normal subjects, 78 patients with liver disease, 30 patients on long-term antiepileptic drug treatment, 9 pregnant women, and 99 unselected hospital patients. 82% of chronic alcoholics had a significantly higher than normal level of phospholipid-esterified 9,11 linoleicacid isomer in blood collected within 24 h of their last alcoholic drink. The levels fell to normal over the next 2-4 days but continued to decline within the normal range for 2-3 weeks. There was no rise in the level of the isomer in normal controls after an acute alcohol load. The results suggest that chronic alcoholism may induce a specific detoxifying mechanism which is activated by alcohol and which entails or depends on greatly increased free-radical activity.

Topics: Adolescent; Adult; Aged; Alcoholism; Cholesterol; Chromatography, High Pressure Liquid; Ethanol; Female; Free Radicals; Humans; Isomerism; Linoleic Acid; Linoleic Acids; Male; Middle Aged; Phospholipids; Reference Values; Substance Withdrawal Syndrome; Triglycerides