Effects of zinc chloride on glutathione and glutathione synthesis rates in various lung cell lines.
Zinc-mediated toxicity has been linked to cellular glutathione (GSH) contents. In this study, effects of zinc on cellular GSH content, glutathione reductase (GR) activity, and GSH synthesis were investigated. In all cell lines tested, decreases in cellular GSH content and GR activity as well as an increase in oxidized glutathione (GSSG) were found after incubation of cells with zinc chloride. These effects were dose- and time-dependent. Changes in GR activities were earliest affected and were most marked compared with the other parameters examined. Decrease of enzyme activity was not due to a decrease in the cosubstrate NADPH. In A549 and L2 cells, initial increases in GSH synthesis rates occurred up to about 175% of control. Later, GSH synthesis decreased to levels below controls. In 16Lu cells, GSH synthesis decreased after 2 h of zinc exposure. No transient increase was found in this cell line. Measurement of ATP content did not show any influence of zinc on cellular ATP. Lactate dehyrogenase leakage, a marker of a clear cytotoxic effect, occurred after 6 h of zinc treatment in the non-malignant cells examined, and after 16 h in malignant A549 cells. We assume the inhibition of GR activity and the associated increase of GSSG could possibly represent a main zinc-mediated toxic cellular effect.
Wilhelm
B
B
Walther Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians Universität Munchen, Munich, Germany.
Walther
U I
UI
Fichtl
B
B
D000818:Animals; D002460:Cell Line; D002712:Chlorides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000633:toxicity; D005978:Glutathione / Q000096:biosynthesis*; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured; D017967:Zinc Compounds / Q000633:toxicity*
D002712:Chlorides; D004791:Enzyme Inhibitors; D017967:Zinc Compounds; C016837:zinc chloride; D005980:Glutathione Reductase; D005978:Glutathione