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Time‐Course Of Changes In Hepatic Lipid Peroxidation And Glutathione Metabolism In Rats With Carbon Tetrachloride‐Induced Cirrhosis
Author(s) -
Cabré M,
Camps J,
Paternáin Jl,
Ferré N,
Joven J
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03322.x
Subject(s) - lipid peroxidation , glutathione , carbon tetrachloride , glutathione peroxidase , cirrhosis , medicine , endocrinology , chemistry , antioxidant , gpx4 , biochemistry , enzyme , organic chemistry
SUMMARY 1. The aims of the present study were to assess: (i) the temporal relationships between hepatic lipid peroxidation, changes in the glutathione detoxification system and the onset/development of cirrhosis in CCl 4 ‐treated rats; and (ii) the effects of oral zinc administration on these parameters. 2. Cirrhosis was induced in 120 rats by intraperitoneal injections of CCl 4 twice a week over 9 weeks. One hundred and twenty additional animals were used as controls. Both groups were further subdivided to receive either a standard diet or one supplemented with zinc. Subsets of 10 animals each were killed at weeks 1, 2, 3, 5, 7 and 9 from the start of the study. 3. Induction of cirrhosis produced a decrease in the components of the hepatic glutathione anti‐oxidant system: glutathione transferase activity decreased from week 1, the concentration of reduced glutathione (GSH) decreased from week 5 and glutathione peroxidase (GPx) activity decreased from week 7. This impairment was chronologically related to an increase in free radical generation. Hepatic lipid peroxidation was significantly correlated with GPx activity ( r = – 0.47; P < 0.001) in CCl 4 ‐treated rats. Zinc administration did not produce any significant improvement of the hepatic glutathione system. 4. In conclusion, cirrhosis induction in rats by CCl 4 administration produced a decrease in the hepatic glutathione anti‐ oxidant system that was related to an increase in free radical production. Furthermore, zinc supplementation produced a reduction in the degree of hepatic injury and a normalization of lipid peroxidation, but not an improvement of the hepatic GSH anti‐oxidant system.