Effect of enlarged glutathione on zinc-mediated toxicity in lung-derived cell lines.
Zinc-mediated toxicity has been linked to cellular glutathione content in isolated cells. In addition, treatment of alveolar epithelial type II cells with glucocorticoids diminishes cellular glutathione content, and this is followed by an increase in zinc-mediated toxicity. The question arises whether an increase in glutathione synthesis might decrease zinc-mediated toxicity. For this purpose an administration of 200 micromol/l N-acetyl-L-cysteine (NAC) was given to the cells, while cysteine was used up to 100 micromol/l. Zinc-mediated toxicity was assessed by measuring protein synthesis inhibition and glutathione dependent parameters. De novo synthesis of glutathione was assessed as compared to controls by N-acetyl-D-cysteine (NADC) treatment. Comparing NAC and NADC treatment no differences in zinc-mediated toxicity were found. Furthermore only in one (of three) cell line tested a significant increase in GSH content by NAC as compared to NADC treatment was achieved. But even in this cell line no changes by zinc-mediated toxicity were found. It is concluded that the cell lines tested can use other sources of cys for glutathione synthesis. Furthermore the increased zinc-mediated toxicity due to hydrocortisone was abolished in the alveolar epithelial cell lines by the NADC/NAC treatment. It is therefore discussed that additionally to glutathione some other antioxidative defence mechanisms can influence zinc-mediated toxicity as well.
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Walther Straub-Institut für Pharmakologie und Toxikologie der Ludwig-Maximilians Universität München, Goethestr. 33, 80336 München, Germany. udo.walther@lrz.uni-muenchen.de
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Temrück
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D000111:Acetylcysteine / Q000633:toxicity*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000633:toxicity*; D005978:Glutathione / Q000096:biosynthesis*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007536:Isomerism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017967:Zinc Compounds / Q000378:metabolism / Q000633:toxicity*
D002712:Chlorides; D004338:Drug Combinations; D016166:Free Radical Scavengers; D017967:Zinc Compounds; C016837:zinc chloride; D005978:Glutathione; D006854:Hydrocortisone; D000111:Acetylcysteine