ETHANOL-INDUCED CHANGES IN THE CONTENT OF THIOL COMPOUNDS AND OF LIPID-PEROXIDATION IN LIVERS AND BRAINS FROM MICE - PROTECTION BY THIAZOLIDINE DERIVATIVES

WLODEK L ROMMELSPACHER H

L. Wlodek et H. Rommelspacher, ETHANOL-INDUCED CHANGES IN THE CONTENT OF THIOL COMPOUNDS AND OF LIPID-PEROXIDATION IN LIVERS AND BRAINS FROM MICE - PROTECTION BY THIAZOLIDINE DERIVATIVES, Alcohol and alcoholism, 29(6), 1994, pp. 649-657

50

INGLESE

Article

Substance Abuse

Alcohol and alcoholism → ACNP

0735-0414

29

6

1994

649 - 657

ISI

0735-0414(1994)29:6<649:ECITCO>2.0.ZU;2-C

Treatment of mice with ethanol for 5 days resulted in a drop of total glutathione in the liver, possibly due to an ethanol-stimulated increa sed conversion into L-cysteine. The levels of L-cysteine and the rate of lipid peroxidation were above control levels. Similar but less pron ounced changes were observed with brain tissue. The continuation of th e treatment with ethanol led to an adaptation in both tissues as asses sed at days 10 and 15. These findings suggest induction of enzymes inv olved in the defence mechanisms against lipid peroxidation. However, a t day 23 of treatment the levels of total glutathione and L-cysteine w ere reduced in the liver whereas lipid peroxidation was increased. Thu s, a state of impaired defence mechanisms occurred during prolonged tr eatment. Interestingly, the concentration of total glutathione was inc reased in the brain suggesting protective mechanisms in this organ and possibly a supply from other organs. No increase of lipid peroxidatio n levels in the brain was observed. The substitution of the deficit of thiol compounds is a major problem because neither L-cysteine nor glu tathione can be utilized for different reasons. Therefore, we treated mice with thiazolidine derivatives which can be regarded as 'frozen' L -cysteine. Two days of treatment with 2-methyl-thiazolidine-2,4-dicarb oxylic acid were sufficient to observe an increase of total glutathion e and free L-cysteine levels and a decrease of lipid peroxidation in t he liver. These findings demonstrate a new treatment for the tissue-da maging effects of chronic ethanol ingestion. However, the administrati on of the same dose of thiazolidine-4-carboxylic acid caused intoxicat ion with neurological symptoms, suggesting that not all thiazolidine d erivatives are suited for the treatment of the deficit of thiols.