Ethanol-induced changes in the content of thiol compounds and of lipid peroxidation in livers and brains from mice: protection by thiazolidine derivatives.
Treatment of mice with ethanol for 5 days resulted in a drop of total glutathione in the liver, possibly due to an ethanol-stimulated increased conversion into L-cysteine. The levels of L-cysteine and the rate of lipid peroxidation were above control levels. Similar but less pronounced changes were observed with brain tissue. The continuation of the treatment with ethanol led to an adaptation in both tissues as assessed at days 10 and 15. These findings suggest induction of enzymes involved in the defence mechanisms against lipid peroxidation. However, at day 23 of treatment the levels of total glutathione and L-cysteine were reduced in the liver whereas lipid peroxidation was increased. Thus, a state of impaired defence mechanisms occurred during prolonged treatment. Interestingly, the concentration of total glutathione was increased in the brain suggesting protective mechanisms in this organ and possibly a supply from other organs. No increase of lipid peroxidation levels in the brain was observed. The substitution of the deficit of thiol compounds is a major problem because neither L-cysteine nor glutathione 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-dicarboxylic acid were sufficient to observe an increase of total glutathione and free L-cysteine levels and a decrease of lipid peroxidation in the liver. These findings demonstrate a new treatment for the tissue-damaging effects of chronic ethanol ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)
Wlodek
L
L
Institute of Medical Biochemistry, Jagiellonian University, Collegium Medicum/Krakow, Poland.
Rommelspacher
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H
D000437:Alcoholism / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D003545:Cysteine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008108:Liver Diseases, Alcoholic / Q000473:pathology*; D008111:Liver Function Tests; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D000975:Antioxidants; D013844:Thiazoles; D053778:Thiazolidines; D008315:Malondialdehyde; C003438:thiazolidine-4-carboxylic acid; D005978:Glutathione; D003545:Cysteine