mitoguazone and diethyl-maleate

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.

Topics: Animals; Carbon Tetrachloride; Cells, Cultured; Cysteine; Cytoprotection; Dose-Response Relationship, Drug; Glutathione; Glutathione Transferase; Hepatocytes; L-Lactate Dehydrogenase; Male; Maleates; Methionine; Mitoguazone; Polyamines; Rats; Rats, Sprague-Dawley; S-Adenosylmethionine; Sulfhydryl Compounds