Abstract
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.
Highlights
Calories as stripped corn oil), high lipid (35% calories as stripped corn oil), or n-3 fatty acid supplementation
The severity of cholestatic liver injury in adults with primary biliary cirrhosis and in bile duct-ligated rats was related to increasing levels of dietary fat intake [7], a situation that may increase the substrate for lipid peroxidation, thereby making the liver more susceptible to oxidant stress [8]
The experiments conducted in this study demonstrate that peroxidative decomposition of mitochondrial lipids occurs in the chronically bile duct ligation and transection (BDL) rat model of cholestatic liver injury
Summary
Calories as stripped corn oil), high lipid (35% calories as stripped corn oil), or n-3 fatty acid (fish oil) supplementation. 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 severity of cholestatic liver injury in adults with primary biliary cirrhosis and in bile duct-ligated rats was related to increasing levels of dietary fat intake [7], a situation that may increase the substrate for lipid peroxidation (polyunsaturated fatty acids), thereby making the liver more susceptible to oxidant stress [8]. The aim of this study was to directly assess whether peroxidation of hepatic mitochondrial lipids is associated with cholestatic liver injury in the bile duct-ligated rat and.
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