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 t he cytoprotective ability of L-cysteine and L-methionine, the most importan t components in the sulfur amino acid metabolic pathway, in carbon tetrachl oride (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. Tr eating with methylglyoxal bis-(guanylhydrazone), MGBG, an irreversible inhi bitor of S-adenosylmethionine decarboxylase, which is a key enzyme in sperm idine and spermine biosynthesis, and therefore used to deplete cellular pol yamines, prevented the protective effect of L-cysteine and L-methionine, bu t the addition of exogenous polyamines inhibited the influence of MGBG. The se results suggest that the cytoprotective effect of L-cysteine and L-methi onine in CCl4-induced toxicity were via maintenance of cellular polyamines, GSH and protein-SH concentrations and prevention of LDH leakage.