Effect of deoxycholic acid and ursodeoxycholic acid on lipid peroxidation in cultured macrophages.
Effect of deoxycholic acid and ursodeoxycholic acid on lipid peroxidation in cultured macrophages.
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脱氧胆酸和熊去氧胆酸对培养巨噬细胞脂质过氧化的影响。
作者：
P. Ljubuncic;B. Fuhrman;J. Oiknine;M. Aviram;A. Bomzon;Israel P Ljubuncic;Israel B Fuhrman;B. Rappaport;Israel M Aviram
背景技术背景：枯否细胞对于正常的肝脏稳态是必需的，并且当受到刺激时，它们分泌活性氧、一氧化氮、类花生酸和细胞因子。其中一些产物具有细胞毒性，攻击核酸、巯基蛋白或膜脂质，导致脂质过氧化。疏水性胆汁酸，如脱氧胆酸（DCA），可通过溶解膜和损害线粒体功能以及增加活性氧的产生来损伤肝细胞。目的：疏水胆汁酸可以刺激枯否细胞，以增加他们的能力，产生活性氧通过测量细胞脂质过氧化的假设进行了测试。由于亲水性胆汁酸熊去氧胆酸（UDCA）可阻断疏水性胆汁酸诱导的细胞现象，因此还假设UDCA可拮抗疏水性胆汁酸对巨噬细胞的激活，从而减弱其产生活性氧的能力。方法：将J-774A.1鼠巨噬细胞与单独的10（-5）M和10（-4）M（终浓度）DCA或单独的10（-4）M UDCA或10（-4）M 1：1摩尔比的DCA和UDCA混合物孵育24小时。在孵育期结束时，收集培养基，通过硫代巴比妥酸反应物质测定法测定培养基中的丙二醛（MDA）含量，测定细胞脂质过氧化反应。结果：10（-5）M和10（-4）M DCA可增加培养的巨噬细胞的MDA生成。10（-4）M UDCA单独使用不增加MDA的生成，但阻断DCA的过氧化作用。结论：疏水性胆汁酸在肝脏滞留后，可氧化激活枯否细胞产生活性氧。由于UDCA可以阻断这种作用，UDCA的有益作用部分与其作为抗氧化剂的能力有关。
BACKGROUND: Kupffer cells are essential for normal hepatic homeostasis and when stimulated, they secrete reactive oxygen species, nitric oxide, eicosanoids, and cytokines. Some of these products are cytotoxic and attack nucleic acids, thiol proteins, or membrane lipids causing lipid peroxidation. Hydrophobic bile acids, such as deoxycholic acid (DCA), can damage hepatocytes by solubilising membranes and impairing mitochondrial function, as well as increasing the generation of reactive oxygen species. OBJECTIVES: The hypothesis that hydrophobic bile acids could stimulate Kupffer cells to increase their capacity to generate reactive oxygen species by measuring cellular lipid peroxidation was tested. Because the hydrophilic bile acid, ursodeoxycholic acid (UDCA) can block hydrophobic bile acid induced cellular phenomena, it was also hypothesised that UDCA could antagonise macrophage activation by hydrophobic bile acids to blunt their capacity to generate reactive oxygen species. METHODS: J-774A.1 murine macrophages were incubated for 24 hours with either 10(-5) M and 10(-4) M (final concentration) DCA alone, or 10(-4) M UDCA alone, or a mixture of 10(-4) M 1:1 molar ratio of DCA and UDCA. At the end of the incubation period, the culture medium was collected for determination of cellular lipid peroxidation by measuring the malondialdehyde (MDA) content in the medium with the thiobarbituric acid reactive substances assay. RESULTS: 10(-5) M and 10(-4) M DCA increased MDA generation by cultured macrophages. 10(-4) M UDCA alone did not increase MDA generation but blocked the peroxidative actions of DCA. CONCLUSIONS: Hydrophobic bile acids, after their hepatic retention, can oxidatively activate Kupffer cells to generate reactive oxygen species. Because UDCA can block this action, the beneficial effect of UDCA is, in part, related to its ability to act as an antioxidant.
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影响因子：
158.5
作者：
JOHNSTON, RB
通讯作者：
JOHNSTON, RB
DOI：
--
发表时间：
1995-02
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
R. Botla;J. Spivey;H. Aguilar;S. Bronk;G. Gores
通讯作者：
R. Botla;J. Spivey;H. Aguilar;S. Bronk;G. Gores
胆汁酸诱导 HCO3-(-)rich 胆汁过多的机制。
影响因子：
25.7
作者：
Anwer,MS
通讯作者：
Anwer,MS
影响因子：
6.5
作者：
D. Heuman
通讯作者：
D. Heuman
DOI：
10.1073/pnas.87.4.1620
发表时间：
1990-02-01
影响因子：
11.1
作者：
BECKMAN, JS;BECKMAN, TW;FREEMAN, BA
通讯作者：
FREEMAN, BA