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AA Nanji, EK Yang, F Fogt, SM Sadrzadeh and AJ Dannenberg
Department of Pathology, New England Deaconess Hospital, Boston, Massachusetts, USA.
Lipid peroxidation may be important in the pathogenesis of alcoholic liver injury. We investigated the potential of medium chain triglycerides and vitamin E to decrease lipid peroxidation and reverse established alcoholic liver injury. Four groups (five rats/group) of male Wistar rats were studied. Rats in group 1 were fed a fish oil- ethanol diet for 6 weeks. Rats in groups 2, 3 and 4 were fed the fish oil-ethanol diet for 6 weeks before being switched to fish oil-dextrose (group 2), fish oil-dextrose plus vitamin E (group 3) or medium chain triglycerides-dextrose (group 4) diets for 2 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, fatty acid composition and cytochrome P450 2E1 activity. By 6 weeks, all rats developed fatty liver, inflammation and necrosis. After switching to the dextrose- containing diets, there was minimal histologic improvement in group 2, moderate improvement in group 3 and near normalization of the histology in group 4. Histologic improvement was associated with decreased lipid peroxidation and cytochrome P450 2E1 activity. Higher levels of polyunsaturated fatty acids were seen in groups 2 and 3 than in group 4. Our results indicate that a diet enriched in saturated (group 4) but not polyunsaturated (group 2) fatty acids effectively reverses alcoholic liver injury. Treatment with vitamin E also led to histologic improvement. These effects may be explained, at least in part, by down- regulation of lipid peroxidation. Other effects of medium chain triglycerides, such as their propensity for oxidation rather than esterification, may also be important.
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