Dynamic aspects of glutathione and nitric oxide metabolism in
endotoxemic rats.
Minamiyama, Yukiko, Shigekazu Takemura, Keiko Koyama, Hidenori Yu,
Masafumi Miyamoto, and Masayasu Inoue.
Department of Biochemistry, Osaka City University Medical School,
1-4-54 Asahimachi, Abeno-ku, Osaka 545, Japan
APStracts 3:0068G, 1996.
Glutathione is one of the most abundant thiols in mammalian tissues
and plays important roles in the defense mechanism and detoxification
of various metabolites, such as reactive xenobiotics and free
radicals. Nitric oxide (NO) readily reacts with thiol compounds
thereby generating chemically stable S-nitrosothiols. Although
endotoxin has been known to induce NO synthase in various organs
particularly liver and spleen and enhances the production of NO,
correlation between NO and glutathione metabolism in endotoxemic
subjects remains to be elucidated. The present work examines the
changes in NO and glutathione metabolism in endotoxemic rats.
Administration of lipopolysaccharide (LPS) markedly decreased the
glutathione levels in plasma and bile, whereas it decreased the
hepatic level only slightly. NG- nitro-L-arginine (LNNA), a NO
synthase inhibitor, inhibited the LPS-induced decrease of glutathione
in plasma and bile. Administration of LPS increased the biliary
levels of [gamma]-glutamyltranspeptidase ([gamma]-GTP) without
affecting its SH levels. Acivicin, a [gamma]-GTP inhibitor, inhibited
the LPS-induced decrease of glutathione in plasma and bile without
affecting its hepatic levels. Analysis using L-buthionine sulfoximine
(BSO) revealed that the turnover of hepatic glutathione significantly
increased in LPS-treated rats by some LNNA inhibitable mechanism.
These results suggest that endotoxin might enhance the NO production
in the liver, and other tissues and significantly modulate the
interorgan metabolism of GSH.
Received 30 October 1995; accepted in final form 15 March 1996.
APS Manuscript Number G472-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 April 96