REMOVED: Glutathione prevents cytochrome P450 3A induction by dexamethasone in primary cultures of rat hepatocytes

Richert, Lysiane; Binda, Delphine; Alexandre, Eliane; Bars, R; Martin, Hélène; Lasserre-Bigot, Dominique

doi:10.1016/j.tiv.2006.07.010

Cited by 1 publication

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“…As a consequence glutathione content of hepatic-derived cells seems to be less dependent on extracellular cys concentrations. Accordingly, Richert et al [21] found a two-to threefold increase in glutathione by NAC in hepatocytes only at 4 mmol/l or above. A differentiation of the NADC (or NAC) effectivity, allocated into complexing or antioxidative properties [22,23], seems to be interesting in the case of the zinc-mediated toxicity.…”

Section: Discussionmentioning

confidence: 97%

Enhancing Glutathione Synthesis can Decrease Zinc-Mediated Toxicity

Walther

Mückter

et al. 2008

Biol Trace Elem Res

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Zinc toxicity has been linked to cellular glutathione: A decrease in glutathione is followed by an increase in zinc-mediated toxicity. The question arises whether an increase in glutathione synthesis might decrease zinc-mediated cytotoxicity. We incubated five cell lines (hepatoma and lung-derived) with zinc chloride and 2 mmol/l N-acetyl-L-cysteine (NAC) to support glutathione synthesis. In all but one hepatic cell line, the glutathione content was increased by NAC as compared to the D-enantiomere NADC, whereas NADC did not increase GSH content as compared to not treated controls. In both alveolar epithelial cell lines, an increase in zinc tolerance was observed due to NAC as compared to NADC. In native fibroblast-like and the hepatoma cell lines, no changes in zinc tolerance were found due to NAC. In the fibroblast-like cells, zinc tolerance was increased due to NAC only after cellular glutathione had been previously decreased (by lowered cysteine concentrations in the medium). Enhancing glutathione synthesis can antagonize zinc-mediated toxicity in the alveolar epithelial cell lines, whereas some other characteristics than glutathione synthesis might be more important in other cell types. Furthermore, NAC acted as a GSH precursor only at cysteine medium concentrations of 10 micromol/l or below and therefore might be described as a poor cysteine repletor for glutathione synthesis.

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Section: Discussionmentioning

confidence: 97%