Geetha Arumugam, Parameswari Somasundaram
P.G. Department of Biochemistry, Bharathi Women's College, North Chennai, 600 108.
Indian J Physiol Pharmacol. 2002 Jul;46(3):343-8.
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.
在体外评估了强力肝保护剂熊去氧胆酸（UDCA）的不同浓度对过氧化氢诱导的线粒体肿胀的影响，以探究该药物的作用机制。将羊肝线粒体等分试样与不同浓度的UDCA（0 - 600微克）预孵育，然后用过氧化氢（1 mM）诱导肿胀。在不同时间间隔评估肿胀情况，同时还评估脂质过氧化物、还原型谷胱甘肽状态。UDCA以剂量依赖的方式使过氧化氢诱导的肿胀最小化。在用过氧化氢处理的线粒体中，脂质过氧化物水平随时间升高，而在UDCA预处理中这种升高最小化。UDCA还能维持线粒体中还原型谷胱甘肽水平。UDCA对抗肝脏线粒体中施加的氧化应激。它减少脂质过氧化诱导的异常，如肿胀和硫醇基团耗竭，并且该药物的抗脂质过氧化功效可能与其亲水性有关，这可能保护易发生自由基介导反应的线粒体膜疏水区域。
