Peres W, Tuñón M J, Collado P S, Herrmann S, Marroni N, González-Gallego J
Department of Physiology, University of León, Spain.
J Hepatol. 2000 Nov;33(5):742-50. doi: 10.1016/s0168-8278(00)80305-0.
BACKGROUND/AIMS: Our aim was to investigate whether the antioxidant quercetin might protect against liver injury in chronically biliary obstructed rats.
Secondary biliary cirrhosis was induced by 28 days of bile duct obstruction. Animals received quercetin at 75, 150 and 300 micromol x kg body wt(-1) x day(-1) i.p. through the experimental period or at 150 micromol x kg body wt(-1) x day(-1) i.p. for the last 2 weeks.
Bile duct obstruction resulted in a decrease in the activities of antioxidant enzymes. Liver oxidised/reduced (GSSG/GSH) glutathione ratio, hepatic and mitochondrial thiobarbituric acid reactive substances (TBARS) and collagen content were significantly increased and a marked fibrosis and bile ductular proliferation was observed. Quercetin corrected the reduction in glutathione concentration and partially prevented the increase in collagen concentration, TBARS and GSSG/GSH ratio. Treatment resulted in a significant preservation of the activities of antioxidant enzymes, a less pronounced fibrosis and a marked inhibition of bile ductular proliferation. Maximal effects were reached with the intermediate quercetin dose given for 2 or 4 weeks.
Quercetin reduces liver oxidative damage, ductular proliferation and fibrosis in biliary-obstructed rats. These effects suggest that it might be a useful agent to preserve liver function in patients with biliary obstruction.
背景/目的:我们的目的是研究抗氧化剂槲皮素是否能保护慢性胆管梗阻大鼠免受肝损伤。
通过28天的胆管梗阻诱导继发性胆汁性肝硬化。在实验期间,动物腹腔注射75、150和300微摩尔/千克体重×天的槲皮素,或在最后2周腹腔注射150微摩尔/千克体重×天的槲皮素。
胆管梗阻导致抗氧化酶活性降低。肝脏氧化型/还原型(GSSG/GSH)谷胱甘肽比值、肝脏和线粒体硫代巴比妥酸反应性物质(TBARS)以及胶原蛋白含量显著增加,并观察到明显的纤维化和胆管增生。槲皮素纠正了谷胱甘肽浓度的降低,并部分阻止了胶原蛋白浓度、TBARS和GSSG/GSH比值的增加。治疗导致抗氧化酶活性显著保留,纤维化减轻,胆管增生明显受到抑制。给予中间剂量的槲皮素2周或4周可达到最大效果。
槲皮素可减轻胆管梗阻大鼠的肝脏氧化损伤、胆管增生和纤维化。这些作用表明它可能是保护胆管梗阻患者肝功能的有用药物。