title: Lipoic acid increases glutathione production and enhances the effect of mercury in human cell lines.
abstract: Thiols are known to influence the metabolism of glutathione. In a previous study (Toxicology 156 (2001) 93) dithiothreitol (DTT) did not show any effect on intra- or extracellular glutathione concentrations in HeLa cell cultures but increased the effects of mercury ions on glutathione concentrations, whereas monothiols such as N-acetylcysteine (NAC) or glutathione did not. In the present study, we have investigated the effects of thiols as well as the interaction between thiols and mercury ions in cultures of both HeLa and hepatoma cells. Furthermore, we have added alpha-lipoic acid (LA) to the previously used test panel of thiols, since it is metabolised intracellularly to a dithiol (dihydrolipoate). The present study shows that LA increased intra- and extracellular concentrations of glutathione in both HeLa and hepatoma cell cultures. In contrast to results for HeLa cells, the presence of DTT increased the intracellular glutathione concentration in hepatoma cells. No increase of glutathione concentrations was observed in hepatoma cell cultures in the presence of the monothiols (NAC, homocysteine or glutathione) tested, in agreement with previous findings in HeLa cell cultures. The presence of dithiols, either DTT or dihydrolipoate (the metabolite of LA), increased the effects of mercury ions on glutathione concentrations in hepatoma cells, whereas monothiols such as NAC or glutathione did not, in agreement with previous findings in HeLa cells. Thus, metabolic effects of mercury ions were observed in hepatoma cells as well as in HeLa cells at a lower concentration than the supposed toxicity threshold for mercury in blood.
authors.affiliation: Department of Clinical Chemistry, Institute of Laboratory Medicine, University Hospital Lund, S-22185 Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Hultberg
authors.forename: Anders
authors.initials: A
authors.lastname: Andersson
authors.forename: Anders
authors.initials: A
authors.lastname: Isaksson
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism*; D004229:Dithiothreitol / Q000378:metabolism; D004357:Drug Synergism; D005978:Glutathione / Q000096:biosynthesis*; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D008628:Mercury / Q000378:metabolism / Q000633:toxicity*; D008063:Thioctic Acid / Q000378:metabolism / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D006710:Homocysteine; D008063:Thioctic Acid; D008628:Mercury; D005978:Glutathione; D004229:Dithiothreitol; D000111:Acetylcysteine