Department of Biochemistry, the University of Nis Medical School, Nis, Serbia.
Drug Chem Toxicol. 2013 Apr;36(2):141-8. doi: 10.3109/01480545.2012.658919. Epub 2012 Mar 2.
Accumulation of hydrophobic bile acids (BAs) during cholestasis plays an important role in apoptosis initiation as well as oxidative stress increase in liver cells. Ursodeoxycholic acid (UDCA) acts as a protector in BA-induced cell injury.The aim of the study was to evaluate the effect of UDCA on oxidative stress level and DNase I and II activity caused by liver injury in bile duct ligation (BDL) rats.Wistar rats were divided in four groups: group 1, control (sham-operated); group 2, sham-operated and injected with UDCA (30 mg/kg); group 3,animals with BDL; and group 4,UDCA-treatedcholestatic rats. Animals were sacrificed after 9 days. Malondialdehyde (MDA; lipid peroxidation end-product) level and protein-molecule oxidative modification (carbonyl group content) significantly increased in BDL rat liver. Catalase (CAT) activity in liver tissue was found to be decreased in BDL rats. In addition, xanthine oxidase (XO) activity, which is thought to be one of the key enzymes producing reactive oxygen species, was found to be increased in the cholestatic group. The apoptotic effect in cholestasis was probably triggered by the increased activation of DNase I and II. The protective effect of UDCA on liver tissue damage in BDL rats, in comparison to cholestatic liver, were 1) decrease of MDA levels, 2) increased CAT activity, 3) reduced XO activity, and 4) effect on terminal apoptotic reaction, shown as a decrease in DNase I and II activity.Therefore, UDCA may be useful in the preservation of liver function in cholestasis treatment.
在胆汁淤积过程中，疏水性胆汁酸（BAs）的积累在细胞凋亡的启动以及肝细胞氧化应激的增加中起着重要作用。熊去氧胆酸（UDCA）在 BA 诱导的细胞损伤中起保护作用。本研究旨在评估 UDCA 对胆管结扎（BDL）大鼠肝损伤诱导的氧化应激水平和 DNA 酶 I 和 II 活性的影响。Wistar 大鼠分为四组：第 1 组，对照组（假手术）；第 2 组，假手术并注射 UDCA（30mg/kg）；第 3 组，BDL 动物；第 4 组，UDCA 治疗性胆郁积大鼠。动物在 9 天后被处死。BDL 大鼠肝组织丙二醛（MDA；脂质过氧化终产物）水平和蛋白质分子氧化修饰（羰基含量）显著增加。肝组织中过氧化氢酶（CAT）活性降低。此外，黄嘌呤氧化酶（XO）活性增加，XO 被认为是产生活性氧的关键酶之一，在胆郁积组中增加。在胆郁积中，凋亡效应可能是由 DNA 酶 I 和 II 的激活增加触发的。与胆郁积肝相比，UDCA 对 BDL 大鼠肝组织损伤的保护作用为：1）MDA 水平降低，2）CAT 活性增加，3）XO 活性降低，4）终末凋亡反应，表现为 DNA 酶 I 和 II 活性降低。因此，UDCA 可能对胆郁积治疗中的肝功能保护有用。
