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Lipoic acid increases glutathione production and enhances the effect of mercury in human cell lines.

Hultberg, Björn LU ; Andersson, Anders S LU and Isaksson, Anders LU (2002) In Toxicology 175(1-3). p.103-110
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... (More)
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. (Less)
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keywords
Non-U.S. Gov't, Thioctic Acid : metabolism, Thioctic Acid : toxicity, Support, Mercury : toxicity, Mercury : metabolism, Human, Homocysteine : metabolism, Hepatocytes : metabolism, Hepatocytes : drug effects, Hela Cells : metabolism, Hela Cells : drug effects, Glutathione : biosynthesis, Drug Synergism, Dithiothreitol : metabolism, Acetylcysteine : metabolism, Antioxidants : metabolism
in
Toxicology
volume
175
issue
1-3
pages
103 - 110
publisher
Elsevier
external identifiers
  • pmid:12049840
  • wos:000176251800010
  • scopus:0037076855
ISSN
0300-483X
DOI
10.1016/S0300-483X(02)00060-4
language
English
LU publication?
yes
id
8d48cdbe-e637-4dc7-b594-f1b97a943259 (old id 108668)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12049840&dopt=Abstract
date added to LUP
2007-07-05 10:36:57
date last changed
2017-06-18 04:34:08
@article{8d48cdbe-e637-4dc7-b594-f1b97a943259,
  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.},
  author       = {Hultberg, Björn and Andersson, Anders S and Isaksson, Anders},
  issn         = {0300-483X},
  keyword      = {Non-U.S. Gov't,Thioctic Acid : metabolism,Thioctic Acid : toxicity,Support,Mercury : toxicity,Mercury : metabolism,Human,Homocysteine : metabolism,Hepatocytes : metabolism,Hepatocytes : drug effects,Hela Cells : metabolism,Hela Cells : drug effects,Glutathione : biosynthesis,Drug Synergism,Dithiothreitol : metabolism,Acetylcysteine : metabolism,Antioxidants : metabolism},
  language     = {eng},
  number       = {1-3},
  pages        = {103--110},
  publisher    = {Elsevier},
  series       = {Toxicology},
  title        = {Lipoic acid increases glutathione production and enhances the effect of mercury in human cell lines.},
  url          = {http://dx.doi.org/10.1016/S0300-483X(02)00060-4},
  volume       = {175},
  year         = {2002},
}