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Glutathione, a first line of defense against cadmium toxicity

Journal Article · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6017125
; ;
Experimental modulation of cellular glutathione levels has been used to explore the role of glutathione in cadmium toxicity. Mice treated with buthionine sulfoximine (an effective irreversible inhibitor of ..gamma..-glutamylcysteine synthetase (EC 6.3.2.2) that decreases cellular levels of glutathione markedly) were sensitized to the toxic effects of CdCl/sub 2/. Mice pretreated with a sublethal dose of Cd/sup 2 +/ to induce metallothionein synthesis were not sensitized to Cd/sup 2 +/ by buthionine sulfoximine were protected against a lethal dose of Cd/sup 2 +/ by glutathione mono isopropyl ester (L-..gamma..-glutamyl-L-cysteinylglycylisopropyl ester), but not by glutathione. These results are in accord with studies that showed that glutathione mono esters (in contrast to glutathione) are efficiently transported into cells and converted intracellularly to glutathione. The findings indicate that intracellular glutathione functions in protection against Cd/sup 2 +/ toxicity, and that this tripeptide provides a first line of defense against Cd/sup 2 +/ before induction of metallothionein synthesis occurs. The experiment approach used here in which cellular levels of glutathione are described or increased seems applicable to investigation of other types of metal toxicity and of other glutathione-dependent biological phenomena.
Research Organization:
Cornell Univ Medical College, New York, NY
OSTI ID:
6017125
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 1:3; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL FUNCTIONS
CADMIUM
CADMIUM COMPOUNDS
DRUGS
ELEMENTS
FUNCTIONS
GLUTATHIONE
MAMMALS
METALS
MICE
ORGANIC COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RODENTS
TOXICITY
VERTEBRATES