Effects of Deoxycholic Acid and Its Epimers on Lipid Peroxidation in Isolated Rat Hepatocytes.

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We studied the effects of deoxycholic acid and its three epimers with β-hydroxyl groups (3α, 12β-, 3β, 12α-, and 3β, 12β-dihydroxy-5β-cholan-24-oic acids), which were hydrophilic and less cytotoxic, on lipid peroxidation to elucidate the relationship between structural features of bile acids and their effect on lipid peroxidation. Taurodeoxycholate markedly increased the production of thiobarbituric acid-reactive substances, end products of lipid peroxidation, in isolated rat hepatocytes, whereas epimers of taurodeoxycholate did not. Deoxycholic acid inhibited mitochondrial NADH dehydrogenase and NADH: ferricytochrome c oxidoreductase activities, leading to free radical generation, whereas epimers of deoxycholic acid had no effect on mitochondrial enzymes. These findings suggested that hydrophobic bile acids cause lipid peroxidation by impairment of mitochondrial function, leading to the generation of free radicals; and epimerization of α-hydroxyl groups in the steroid nucleus to β-hydroxyl groups results in a decrease of the toxic effects of deoxycholic acid on lipid peroxidation.
社団法人日本生化学会の論文