Effects of deoxycholic acid and its epimers on lipid peroxidation in isolated rat hepatocytes

We studied the effects of deoxycholic acid and its three epimers with beta -hydroxyl groups (3 alpha ,12 beta-, 3 beta ,12 alpha-, and 3 beta ,12 beta -dihydroxy-5 beta -cholan-24-oic acids), which were hydrophilic and less c ytotoxic, on lipid peroxidation to elucidate the relationship between struc tural features of bile acids and their effect on lipid peroxidation. Taurod eoxycholate markedly increased the production of thiobarbituric acid-reacti ve substances, end products of lipid peroxidation, in isolated rat hepatocy tes, whereas epimers of taurodeoxycholate did not. Deoxycholic acid inhibit ed mitochondrial NADH dehydrogenase and NADH:ferricytochrome c oxidoreducta se activities, leading to free radical generation, whereas epimers of deoxy cholic acid had no effect on mitochondrial enzymes. These findings suggeste d that hydrophobic bile acids cause lipid peroxidation by impairment of mit ochondrial function, leading to the generation of free radicals; and epimer ization of alpha -hydroxyl groups in the steroid nucleus to beta -hydroxyl groups results in a decrease of the toxic effects of deoxycholic acid on li pid peroxidation.