Polyamines and thiols in the cytoprotective effect of L-cysteine and L-methionine on carbon tetrachloride-induced hepatotoxicity.
The relationship between cellular glutathione (GSH), protein-SH levels, and lactate dehydrogenase (LDH), with respect to the effect of polyamines on the cytoprotective ability of L-cysteine and L-methionine, the most important components in the sulfur amino acid metabolic pathway, in carbon tetrachloride (CCl4)-induced toxicity in isolated rat hepatocytes was studied. CCl4 induced a LDH release and decreased cellular thiols and polyamines levels but treatment with L-cysteine and L-methionine reversed these decreases. Treating with methylglyoxal bis-(guanylhydrazone), MGBG, an irreversible inhibitor of S-adenosylmethionine decarboxylase, which is a key enzyme in spermidine and spermine biosynthesis, and therefore used to deplete cellular polyamines, prevented the protective effect of L-cysteine and L-methionine, but the addition of exogenous polyamines inhibited the influence of MGBG. These results suggest that the cytoprotective effect of L-cysteine and L-methionine in CCl4-induced toxicity were via maintenance of cellular polyamines, GSH and protein-SH concentrations and prevention of LDH leakage.
Chen
W
W
Department of Food and Nutrition, Faculty of Human Life Science, Osaka City University, Osaka, Japan.
Kennedy
D O
DO
Kojima
A
A
Matsui-Yuasa
I
I
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002478:Cells, Cultured; D003545:Cysteine / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000494:pharmacology; D008715:Methionine / Q000494:pharmacology*; D008935:Mitoguazone / Q000494:pharmacology; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000037:antagonists & inhibitors; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D008298:Maleates; D011073:Polyamines; D013438:Sulfhydryl Compounds; D012436:S-Adenosylmethionine; D008715:Methionine; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D005982:Glutathione Transferase; C014476:diethyl maleate; D005978:Glutathione; D003545:Cysteine; D008935:Mitoguazone