Premium
ALTERED LIPID PEROXIDATION/GLUTATHIONE RATIO IN EXPERIMENTAL EXTRAHEPATIC CHOLESTASIS
Author(s) -
Panozzo M. P.,
Basso D.,
Balint L.,
Biasin M. R.,
Bonvicini P.,
Metus P.,
Infantoho D.,
Plebani M.
Publication year - 1995
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 - 10.1111/j.1440-1681.1995.tb01992.x
Subject(s) - lipid peroxidation , cholestasis , glutathione , chemistry , medicine , endocrinology , gpx4 , biochemistry , oxidative stress , enzyme , glutathione peroxidase
SUMMARY 1. Lipid peroxidation can occur in the presence of a cellular antioxidant‐oxidant imbalance, but the role of lipid peroxides in cholestasis is not well understood. 2. This study was undertaken in order to: (i) evaluate the behaviour of a product of lipid peroxidation (thiobarbituric acid‐reactive species), and of an important antioxidant tripeptide, reduced glutathione, in the course of experimental extrahepatic cholestasis; and (ii) ascertain whether there was a link between this aspect and the alterations in liver morphology. 3. Forty‐five male Sprague‐Dawley rats (250–300 g) were double bile duct ligated and followed from 1 to 28 days. At the end of each experimental period, blood and liver samples were collected for thiobarbituric acid‐reactive species and glutathione determinations. 4. Bile duct ligated rats showed a marked increase in liver weight which was related to cholestasis duration and to some anatomical alterations such as bile duct proliferation and dilation and liver fibrosis (periportal, perivenular, perineoductular and parenchymal). 5. An increase in serum lipid peroxidation was also observed but this was not linked to hepatic thiobarbiturie acid‐reactive species. Erythrocyte and hepatic glutathione decreased in relation to cholestasis duration. Serum lipid peroxides and erythrocyte glutathione were correlated with liver cell necrosis. 6. In conclusion, experimental extrahepatic cholestasis determines bile duct proliferation and fibrosis, the degree of which is directly related to the duration of cholestasis itself and to liver cell necrotic phenomena. Furthermore, extrahepatic cholestasis is associated with increased lipid peroxide formation and with a depletion of reduced glutathione both in the liver and in the erythrocytes. The alteration in the oxidative balance may be a contributory factor in necrotic liver cell phenomena.