The effects of bucillamine on glutathione and glutathione-related enzymes in the mouse.
The effect of bucillamine (BA) on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of high doses of BA (150-400 mg/kg) produced a dose-dependent depletion (20-44%) of hepatic GSH, which was similar in magnitude to that produced by equimolar doses of other sulphydryl drugs studied previously. GSH depletion after acute BA administration correlated well with the elevation of serum glutamic-pyruvic transaminase (SGPT) (6-9-fold increase above control). The increase in SGPT after chronic administration (7 days), although significantly higher than the controls, was however much less than after acute administration. The hepatic GSH concentrations of mice given 7 days of BA were similar to the controls, again correlating well with SGPT activity. Administration of BA (150-400 mg/kg) caused also a significant dose-dependent increase in the oxidized glutathione (GSSG) in blood by 2-7-fold, as well as a dose-dependent increase in blood glutathione S-transferase (GST) activity (2-13-fold). In an in vitro experiment, hepatic GST activity was activated by various concentrations of BA (1 microM-1mM). There was little or no effect on GSSG reductase and on glutathione peroxidase (GSH-Px) after acute administration of BA. Chronic administration of BA had no effect on hepatic GSSG reductase and GSH-Px, but GSSG reductase activity in blood was increased significantly by 4-fold. It is possible that BA may affect the redox status through auto-oxidation and oxidation with endogenous thiols such as glutathione, affecting GSH concentrations and the GSH/GSSG ratio in tissues and, thus, having both metabolic and toxicological consequences. Whether or not the induction of GST activity in vivo in blood and in vitro in liver enzyme preparations shared the same underlying mechanism(s) requires further investigation.
Yeung
J H
JH
Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T.
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase / Q000187:drug effects* / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects* / Q000378:metabolism; D005982:Glutathione Transferase / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010084:Oxidation-Reduction
D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D000410:Alanine Transaminase; D005978:Glutathione; D003545:Cysteine; C026535:bucillamine; D019803:Glutathione Disulfide