Antioxidant properties of tauroursodeoxycholic acid towards free radicals revisited

Antioxidant properties of tauroursodeoxycholic acid (TUDCA), a cytoprotective bile acid, toward free radicals-induced oxidation of lipids were studied in different model systems using EPR oximetry, EPR spin trapping and the FOX-2 method. Various generators of free radicals were tested: Victoria Blue as a type I sensitizer with minimal generation of singlet oxygen (Φ_Δ ≈ 0.2%), hydrophilic (Fe(III)-ADP) and hydrophobic (Fe(III)-8HQ) ferric ion complexes and thermolabile, hydrophilic azo compound (AAPH). The rate of free radicals-induced lipid peroxidation was shown to be reduced by TUDCA in the tested systems. The significant efficiency of TUDCA in retarding LOOH accumulation when lipid oxidation was induced by a hydrophobic ferric ion complex suggests that TUDCA is associated with membranes and operates most efficiently in a lipophilic environment. The efficiency of TUDCA to inhibit peroxidation of lipids induced by free radicals generated in a Fenton-type reaction suggests that the compound may chelate iron ions, thereby reducing their redox activity. Calculations performed using the DOCER algorithm support this hypothesis, indicating that the interaction energies of TUDCA with iron ions fall between those of the two reference models: 8HQ- and the ADP-iron ion complex. This confirms an intermediate interaction pattern.