Effects of silver in isolated rat hepatocytes.
Addition of silver nitrate or silver lactate to freshly isolated hepatocytes caused dose-dependent loss of cell viability, measured by trypan blue exclusion, at concentrations within 30-70 microM. Silver cytotoxicity was accompanied by a decrease in hepatic thiol concentration and an increase in lipid peroxidation. Treatment of hepatocytes with the reduced glutathione (GSH)-depleting agent diethylmaleate markedly increased their vulnerability to silver toxicity whereas protective effects were produced by the thiol-reducing agent, dithiothreitol. Both alpha-tocopherol, which protected from the onset of silver-associated lipid peroxidation, and the iron chelator agent, deferoxamine failed to prevent loss of cell viability. These data suggest that perturbation of intracellular thiol homeostasis may play a critical role in the mechanism underlying silver-induced lethal damage to isolated rat hepatocytes.
Baldi
C
C
Department of Internal Medicine, University of Pavia, Italy.
Minoia
C
C
Di Nucci
A
A
Capodaglio
E
E
Manzo
L
L
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012834:Silver / Q000633:toxicity*
D008054:Lipid Peroxides; D012834:Silver; D005978:Glutathione