Laboratorio Dr. Fernando Cañas, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Pabellón Argentina, 2do. Piso, Ciudad Universitaria, 5000 Córdoba, Argentina.
Comp Biochem Physiol A Mol Integr Physiol. 2012 Aug;162(4):397-405. doi: 10.1016/j.cbpa.2012.04.016. Epub 2012 Apr 27.
High concentrations of sodium deoxycholate (NaDOC) produce toxic effects. This study explores the effect of a single high concentration of NaDOC on the intestinal Ca(2+) absorption and the underlying mechanisms. Chicks were divided into two groups: 1) controls and 2) treated with different concentrations of NaDOC in the duodenal loop for variable times. Intestinal Ca(2+) absorption was measured as well as the gene and protein expressions of molecules involved in the Ca(2+) transcellular pathway. NaDOC inhibited the intestinal Ca(2+) absorption, which was concentration dependent. Ca(2+)-ATPase mRNA decreased by the bile salt and the same occurred with the protein expression of Ca(2+)-ATPase, calbindin D(28k) and Na(+)/Ca(2+) exchanger. NaDOC produced oxidative stress as judged by ROS generation, mitochondrial swelling and glutathione depletion. Furthermore, the antioxidant quercetin blocked the inhibitory effect of NaDOC on the intestinal Ca(2+) absorption. Apoptosis was also triggered by the bile salt, as indicated by the TUNEL staining and the cytochrome c release from the mitochondria. As a compensatory mechanism, enzyme activities of the antioxidant system were all increased. In conclusion, a single high concentration of NaDOC inhibits intestinal Ca(2+) absorption through downregulation of proteins involved in the transcellular pathway, as a consequence of oxidative stress and mitochondria mediated apoptosis.
高浓度的脱氧胆酸钠（NaDOC）会产生毒性作用。本研究探讨了单一高浓度 NaDOC 对肠道 Ca(2+)吸收的影响及其潜在机制。将小鸡分为两组：1）对照组和 2）在十二指肠环中用不同浓度的 NaDOC 处理不同时间。测量肠道 Ca(2+)吸收以及参与 Ca(2+)细胞内途径的分子的基因和蛋白表达。NaDOC 抑制肠道 Ca(2+)吸收，且呈浓度依赖性。胆汁盐使 Ca(2+)-ATPase mRNA 减少，Ca(2+)-ATPase、钙结合蛋白 D(28k)和 Na(+)/Ca(2+)交换蛋白的蛋白表达也同样如此。NaDOC 产生氧化应激，如 ROS 生成、线粒体肿胀和谷胱甘肽耗竭所表明的那样。此外，抗氧化剂槲皮素阻断了 NaDOC 对肠道 Ca(2+)吸收的抑制作用。如 TUNEL 染色和线粒体中细胞色素 c 释放所表明的那样，胆汁盐还引发了细胞凋亡。作为一种代偿机制，抗氧化系统的酶活性均增加。总之，单一高浓度的 NaDOC 通过下调细胞内途径中涉及的蛋白来抑制肠道 Ca(2+)吸收，这是氧化应激和线粒体介导的细胞凋亡的结果。
