Effect of ursodeoxycholic acid on hydrogen peroxide induced lipid peroxidation in sheep liver mitochondria.

ABSTRACT

The effect of various concentrations of ursodeoxycholic acid (UDCA), a potent hepatoprotective agent on hydrogen peroxide-induced mitochondrial swelling was evaluated in vitro to find out the mechanism of action of the drug. Aliquots of sheep liver mitochondria were pre-incubated with various concentrations of UDCA [0-600 micrograms] and swelling was induced by hydrogen peroxide [1 mM]. Swelling was assessed at various time intervals and lipid peroxide, reduced glutathione status were also evaluated simultaneously. UDCA minimized hydrogen peroxide-induced swelling in a dose-dependent manner. Time-dependent elevation in the level of lipid peroxides was noted in mitochondria treated with hydrogen peroxide and this elevation was minimized in UDCA pre-treatment. UDCA also maintains the reduced glutathione level in mitochondria. UDCA acts against the oxidative stress imposed in liver mitochondria. It reduces lipid peroxidation-induced abnormalities such as swelling and thiol group depletion and the anti lipid peroxidative efficacy of the drug may be related to its hydrophilic nature which might protect the hydrophobic regions of the mitochondrial membranes which are prone for free radical-mediated reactions.