title: Response of endogenous reduced glutathione through hepatic glutathione redox cycle to enhancement of hepatic lipid peroxidation with the development of acute liver injury in mice intoxicated with carbon tetrachloride.
abstract: In the liver of male ddY mice intoxicated once with carbon tetrachloride (CCl4), the change in lipid peroxide (LPO) level with the development of damage over a 24 hr period after i.p. treatment of the toxicant (1.0 mL/kg) was compared with the changes in reduced glutathione (GSH) and oxidized glutathione (GSSG) levels, GSSG/GSH ratio, and activities of the glutathione redox cycle-related enzymes such as Se-dependent glutathione peroxidase (Se-GSH-px), glutathione reductase (GSSG reductase), and glucose-6-phosphate dehydrogenase (G-6-PDH) and of Se-independent glutathione peroxidase (non-Se-GSH-px) with the development of damage during the same period. An apparent liver injury was observed 0.5 hr after CCl4 treatment and the injury progressed rapidly later than 8 hr, judging from the activities of serum transaminases, marker enzymes of liver cell damage. Hepatic LPO level slightly increased once during the first 4 hr after CCl4 treatment and a marked increase in the level occurred later than 12 h, while serum LPO level increased later than 12 h. Hepatic GSH level decreased rapidly during the first 4 hr after CCl4 treatment and the decreased level recovered slowly thereafter, although the recovered level did not reach the control level. Hepatic GSSG level rapidly increased once during the first 1 hr after CCl4 treatment and an increase in the level occurred again later than 12 h. Hepatic GSSG/GSH increased during the first 1 hr and later than 8 hr after CCl4 treatment, although the ratio was maintained above the control level later than 0.5 h. Hepatic Se-GSH-px activity increased during the first 2 hr after CCl4 treatment and later than 8 h, while hepatic non-Se-GSH-px activity increased during the first 1 hr but decreased below the control level at 8 and 12 h. Hepatic GSSG reductase activity decreased during the first 2 hr after CCl4 treatment but the decrease activity returned up to the control level at 8 h. Hepatic G-6-PDH activity increased rapidly during the first 2 hr after CCl4 treatment and the increase proceeded slowly thereafter. These results indicate that although hepatic lipid peroxidation is enhanced at early and progressed stages of liver injury in mice intoxicated once with CCl4, endogenous GSH through hepatic glutathione redox cycle can respond well to enhanced hepatic lipid peroxidation at an early stage of liver injury but not enough to enhanced hepatic lipid peroxidation at a progressed stage of liver injury.
authors.affiliation: Department of Biochemistry, School of Medicine, Fujita Health University, Aichi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nishida
authors.forename: Y
authors.initials: Y
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Kongo
authors.forename: I
authors.initials: I
authors.lastname: Ishiguro
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction
chemical_list: D002251:Carbon Tetrachloride; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D019803:Glutathione Disulfide