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Journal of Lipid Research, Vol 32, 1349-1357, Copyright © 1991 by Lipid Research, Inc.
Effect of dietary lipid and vitamin E on mitochondrial lipid peroxidation and hepatic injury in the bile duct-ligated rat
RJ Sokol, M Devereaux and RA Khandwala
Department of Pediatrics, University of Colorado School of Medicine, Denver.
To assess whether lipid peroxidation of hepatic mitochondria is associated
with cholestatic hepatic injury we examined the effect of bile duct
ligation (BDL) versus sham surgery on mitochondrial lipids of rats
maintained on one of seven diets. Diets included vitamin E- deficient (E-)
and vitamin E-sufficient (E+) combined with normal lipid (11.9% calories as
stripped corn oil), high lipid (35% calories as stripped corn oil), or n-3
fatty acid (fish oil) supplementation. Rats were killed 17 days after
surgery, mitochondria were isolated by differential centrifugation, and
lipid-conjugated dienes and thiobarbituric acid-reacting substances (TBARS)
were measured in mitochondrial lipids as indices of lipid peroxidation. BDL
resulted in significant increases in lipid peroxidation in all dietary
groups. The E- high lipid diets (with either corn oil or fish oil) were
associated with higher lipid peroxide and serum bilirubin values in BDL
rats compared to the normal lipid diets. Fish oil supplementation did not
ameliorate cholestatic or oxidative injury. Serum alanine aminotransferase,
bilirubin, alkaline phosphatase, and cholylglycine levels correlated
significantly with levels of mitochondrial conjugated dienes and TBARS.
These data suggest that free radical stress occurs during BDL in the rat
and may result in mitochondrial lipid peroxidation, and that diets high in
lipid may increase free radical damage to hepatic mitochondria. The role of
free radicals in cholestatic hepatic injury requires further investigation.

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Copyright © 1991 by the American Society for Biochemistry and Molecular Biology.
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