Effect of chronic acetaldehyde intoxication on ethanol tolerance and membrane fatty acids.

Recent studies have suggested that acetaldehyde participates directly in the pathogenesis of alcoholism. Its action has been attributed mainly to its physico-chemical properties. Results of direct intoxication of laboratory animals with acetaldehyde have been reported, but only for short periods of exposure and at high doses. These are probably not representative of the conditions found during alcohol intoxication. The pulmonary route of administration described here enables long term intoxication with acetaldehyde, at levels corresponding to values measured during chronic ethanol intoxication. Chronic administration of acetaldehyde during 3 weeks induced a metabolic tolerance to ethanol as tested by the sleeping time after a challenge dose of ethanol; behavioural tolerance (measured by blood alcohol levels on waking) was not observed. At the end of the intoxication, phospholipid fatty acids of erythrocyte and synaptosome membranes were also analysed. Small changes in levels of the shorter fatty acids were observed in the phosphatidyl-choline fraction. By comparison with the effects of ethanol on the same membrane preparations, only a small part of this effect can be attributed to acetaldehyde. The first metabolite of ethanol has, however, a sure effect on the pattern of fatty acid phospholipids.

Ethanol tolerance in the rat after inhalation of acetaldehyde for a period of 21 days.

Ethanol tolerance is related to alterations in fatty acid content and physical properties of membranes. Studies have suggested a specific role for acetaldehyde in the pathogenesis of alcoholism. We measured tolerance to EtOH and erythrocyte membrane fatty acid composition after intoxication by continuous inhalation of AcH vapor for a period of 21 days. Pathophysiological and nutritional parameters were compared between treated and pair weight controls. We showed that: intoxication with AcH is technically possible via the pulmonary route, producing plasma AcH levels comparable to those seen after ethanol intoxication. The dose of AcH needs to be increased progressively to maintain constant plasma levels this indicates metabolic tolerance. the AcH-intoxicated animals had a metabolic tolerance to EtOH. AcH intoxication led to alterations in fatty acid composition similar to those seen after EtOH intoxication, especially in the saturated/unsaturated ratio of the phosphatidyl-choline and phosphatidyl-inositol fractions. AcH probably plays a part in the phenomenon of tolerance to EtOH.