A dose of
diquat below the amount injurious to
selenium-replete animals causes lipid peroxidation and massive liver
necrosis in
selenium-deficient rats. The current study was undertaken to characterize the lipid peroxidation with respect to the liver injury and to correlate the presence of several
selenoproteins with the protective effect of
selenium. Lipid peroxidation was assessed by measurement of
F2 isoprostanes.
Diquat caused an increase in liver and plasma F2 isoprotanes. A gradient of these compounds was detected across the liver in some animals, indicating that this organ was a source of some of the plasma
F2 isoprostanes. A time-course experiment showed that liver
F2 isoprostane concentration increased before plasma
alanine transaminase (ALT) levels rose.
Selenium-deficient rats were injected with
selenium doses from 2 to 50 micrograms/kg and studied 12 hours later. A dose of 10 micrograms/kg or more prevented
diquat-induced lipid peroxidation and liver injury. This dose increased plasma
selenoprotein P substantially, and a dose-response was present. Liver cellular and plasma
glutathione peroxidase activities remained below 2% of their values in control rats for all
selenium doses. In
selenium-deficient rats given
diquat, hepatic lipid peroxidation precedes hepatic
necrosis and could therefore be an important mechanism of the
necrosis.
Selenoprotein P levels were increased by
selenium injections, which protected against
diquat injury, but
glutathione peroxidase activity was not increased. This is consistent with
selenoprotein P being the mediator of the
selenium effect.