EFFECT OF BILE-ACIDS ON LIPID-PEROXIDATION - THE ROLE OF IRON

The toxic effect of hydrophobic bile acids is claimed to be in part me diated by lipid peroxidation. Conversely, antioxidant properties of ta uroursodeoxycholic acid (TUDC), a hydrophilic bile acid, have been sug gested as a possible mechanism by which TUDC confers its beneficial ef fect in a variety of diseases. We have investigated the effect of taur odeoxycholic acid (TDC), a hydrophobic bile acid and TUDC on lipid per oxidation using a pure lipid system both in the presence and absence o f iron ions. Neither TDC nor TUDC showed any effect on spontaneous lip id peroxidation of phosphatidylcholine liposomes or sodium arachidonat e solution. This lack of effect excludes the possibility of direct pro oxidant or antioxidant properties for TDC and TUDC, Addition of ferrou s ions (0.1 mM) to the lipid system brought about a linear increase in lipid peroxidation with time. The presence of TDC caused an increase in the rate and extent of iron-stimulated lipid peroxidation. The prop ensity of bile acids to increase iron-induced lipid peroxidation was r elated to hydrophobicity of the individual bile acids, with the highes t effect observed with taurolithocholic acid, whereas TUDC did not hav e any influence. The TDC-induced increase in the iron-stimulated lipid peroxidation was concentration dependent. Addition of TUDC (10 mM) co mpletely abolished the effect of TDC (2 mM) on iron-induced lipid pero xidation. This finding suggests that TUDC does not function as an anti oxidant per se but may prevent lipid peroxidation caused by TDC. In co nclusion, only in the presence of iron ions, hydrophobic bile acids ma y enhance Lipid peroxidation. TUDC has no antioxidant activity per se but may counter the TDC-induced increase in iron-stimulated lipid pero xidation. (C) 1998 Elsevier Science Inc.