Document Detail


Effects of zinc chloride on glutathione and glutathione synthesis rates in various lung cell lines.
MedLine Citation:
PMID:  11693178     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
B Wilhelm; U I Walther; B Fichtl
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Archives of toxicology     Volume:  75     ISSN:  0340-5761     ISO Abbreviation:  Arch. Toxicol.     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-11-05     Completed Date:  2002-03-19     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0417615     Medline TA:  Arch Toxicol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  388-94     Citation Subset:  IM    
Affiliation:
Walther Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians Universität Munchen, Munich, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Chlorides / toxicity*
Dose-Response Relationship, Drug
Enzyme Inhibitors / toxicity
Glutathione / biosynthesis*
Glutathione Reductase / antagonists & inhibitors,  metabolism
Humans
Lung / drug effects*,  metabolism
Oxidation-Reduction
Rats
Time Factors
Tumor Cells, Cultured
Zinc Compounds / toxicity*
Chemical
Reg. No./Substance:
0/Chlorides; 0/Enzyme Inhibitors; 0/Zinc Compounds; 70-18-8/Glutathione; 7646-85-7/zinc chloride; EC 1.8.1.7/Glutathione Reductase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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