Free radicals and not acetaldehyde influence the circulating levels of glutathione after acute or chronic alcohol abuse: in vivo and in vitro studies.
BACKGROUND
The oxidation of ethanol and acetaldehyde enhances the production of various free radicals involved in membrane lipoperoxidation, and decreases glutathione levels.


OBJECTIVE
We evaluated the effects of acute and chronic ethanol use in vivo, with or without the administration of S-adenosyl-methionine (SAME, 2 g I.v.), and the effects of ethanol and acetaldehyde in vitro, on the erythrocyte levels of malonyldialdehyde and glutathione, and of its principal synthesizing enzymes, gamma-glutamyl-cysteine-synthetase and glutathione-synthetase.


METHODS
Twelve healthy volunteers (age range 26-44 years, median 32 years) and 20 chronic alcohol abusers without liver disease (age range 26-57 years, median 44 years) were studied. Malonyldialdehyde was evaluated by thiobarbituric acid; glutathione and its enzymes by high performance liquid chromatography using a fluorescent detector.


RESULTS
In the healthy subjects, an acute load of ethanol induced a significant decrease in plasma levels of glutathione, which was inhibited by the infusion of S-adenosyl-methionine. In the erythrocytes of alcoholic patients, glutathione and glutathione-synthetase were decreased while malonyldialdehyde was increased. In vitro, acetaldehyde did not affect either the glutathione or the glutathione-related enzyme levels.


CONCLUSIONS
Our data suggest that the alterations in glutathione metabolism in the erythrocytes of alcoholics may be due principally to the production of free radicals, as supported by the high levels of malonyldialdehyde observed.
Loguercio
C
C
Second University of Naples, Italy.
Clot
P
P
Albano
E
E
Argenzio
F
F
Grella
A
A
De Girolamo
V
V
Delle Cave
M
M
Del Vecchio Bianco
C
C
Nardi
G
G
D000079:Acetaldehyde / Q000097:blood / Q000378:metabolism; D000208:Acute Disease; D000328:Adult; D000435:Alcoholic Intoxication / Q000097:blood / Q000378:metabolism; D000437:Alcoholism / Q000097:blood / Q000378:metabolism*; D002908:Chronic Disease; D004912:Erythrocytes / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000097:blood / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism
D005609:Free Radicals; D000431:Ethanol; D008315:Malondialdehyde; D005978:Glutathione; D000079:Acetaldehyde