PATHOGENESIS OF DIQUAT-INDUCED LIVER NECROSIS IN SELENIUM-DEFICIENT RATS - ASSESSMENT OF THE ROLES OF LIPID-PEROXIDATION AND SELENOPROTEIN-P

Citation
Rf. Burk et al., PATHOGENESIS OF DIQUAT-INDUCED LIVER NECROSIS IN SELENIUM-DEFICIENT RATS - ASSESSMENT OF THE ROLES OF LIPID-PEROXIDATION AND SELENOPROTEIN-P, Hepatology, 21(2), 1995, pp. 561-569
Citations number
34
Categorie Soggetti
Gastroenterology & Hepatology
Journal title
ISSN journal
02709139
Volume
21
Issue
2
Year of publication
1995
Pages
561 - 569
Database
ISI
SICI code
0270-9139(1995)21:2<561:PODLNI>2.0.ZU;2-4
Abstract
A dose of diquat below the amount injurious to selenium-replete animal s causes lipid peroxidation and massive liver necrosis in selenium def icient rats. The current study was undertaken to characterize the lipi d peroxidation with respect to the fiver injury and to correlate the p resence of several selenoproteins with the protective effect of seleni um. Lipid peroxidation was assessed by measurement of F-2 isoprostanes Diguat caused an increase in liver and plasma F-2 isoprostanes. A gra dient of these compounds was detected across the liver in some animals , indicating that this organ was a source of some of the plasma F-2 is oprostanes. A time-course experiment showed that liver F-2 isoprostane concentration increased before plasma alanine transaminase (ALT) leve ls rose. Selenium-deficient rats were in jected with selenium doses fr om 2 to 50 mu g/kg and studied 12 hours later. A dose of 10 mu g/kg or more prevented diquat induced lipid peroxidation and liver injury, Th is dose increased plasma selenoprotein P substantially, and a dose-res ponse was present. Liver cellular and plasma glutathione peroxidase ac tivities remained below 2% of their values in control rats for all sel enium doses. In selenium-deficient rats given diquat, hepatic lipid pe roxidation precedes hepatic necrosis and could therefore be an importa nt mechanism of the necrosis. Selenoprotein P levels were increased by selenium injections, which protected against diquat injury, but gluta thione peroxidase activity was not increased. This is consistent with selenoprotein P being the mediator of the selenium effect.