Modulation of cadmium chloride toxicity by sulphur amino acids in hepatoma cells.
Cadmium is a toxic metal and no effective antidote exists at present. The aim of this study was to examine whether sulphur amino acids, involved in glutathione synthesis, can modulate cadmium toxicity in vitro. Two hepatoma cell lines (HepG2 and HTC cells) were exposed to cadmium chloride (0-100 microM) for 8h in control media or in media containing 1mM of homocysteine, cysteine or cystathionine. Cell viability was then assessed with the neutral red assay. In order to assess the mechanism by which homocysteine and cysteine modulate cadmium toxicity their ability to scavenge reactive oxygen species was determined as well as the potential to increase intracellular glutathione levels. The ability of the sulphur amino acids to prevent cadmium uptake by HTC and HepG2 cells was also assessed. The results indicate that homocysteine and cysteine protect efficiently both cell lines from cadmium chloride toxicity whereas cystathionine protects efficiently HTC cells but not HepG2 cells. This effect was shown to be dependent on the dose of each amino acid and increased protection from cadmium was observed with increasing concentrations of homocysteine and cysteine. Both amino acids prevented the formation of reactive oxygen species only when they were administered together with cadmium chloride. In addition homocysteine and cysteine did not increase intracellular glutathione levels. The results indicate that the mechanism by which sulphur amino acids protect from cadmium toxicity in vitro is due to the reduced uptake of the metal by the cells possibly by direct binding to the -SH group of the amino acids.
Fotakis
George
G
Department of Pharmacy, Franklin Wilkins Building, 150 Stamford Street, King's College, London SE1 8WA, United Kingdom.
Timbrell
John A
JA
D019256:Cadmium Chloride / Q000378:metabolism / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D003540:Cystathionine / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology*; D019610:Cytoprotection; D005978:Glutathione / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D014407:Tumor Cells, Cultured
D006710:Homocysteine; D003540:Cystathionine; D005978:Glutathione; D019256:Cadmium Chloride; D003545:Cysteine