Sodium deoxycholate inhibits chick duodenal calcium absorption through oxidative stress and apoptosis

• Published in: Comparative biochemistry and physiology. Part A, Molecular & integrative physiology Molecular & integrative physiology, 2012-08, Vol.162 (4), p.397-405
• Main Authors: Rivoira, María A., Marchionatti, Ana M., Centeno, Viviana A., Díaz de Barboza, Gabriela E., Peralta López, María E., Tolosa de Talamoni, Nori G.
• Format: Article
• Language: English
• Subjects: absorption; Animals; antioxidant activity; antioxidants; Antioxidants - metabolism; Antioxidants - pharmacology; Apoptosis; Avian Proteins - genetics; Avian Proteins - metabolism; bile salts; Ca2-transporting ATPase; calbindin; Calbindins; calcium; Calcium - metabolism; Chickens - metabolism; chicks; cytochrome c; Cytochromes c - metabolism; Deoxycholic Acid - pharmacology; Deoxycholic Acid - physiology; Duodenum - metabolism; Enterocytes - metabolism; enzyme activity; Gene Expression; genes; glutathione; Intestinal Absorption; Intestinal calcium absorption; Intestinal Mucosa - cytology; Intestinal Mucosa - enzymology; Intestinal Mucosa - physiology; messenger RNA; mitochondria; Mitochondria - metabolism; Oxidative Stress; Plasma Membrane Calcium-Transporting ATPases - genetics; Plasma Membrane Calcium-Transporting ATPases - metabolism; protein synthesis; quercetin; Quercetin - pharmacology; Reactive Oxygen Species - metabolism; S100 Calcium Binding Protein G - genetics; S100 Calcium Binding Protein G - metabolism; Sodium deoxycholate; Sodium-Calcium Exchanger - genetics; Sodium-Calcium Exchanger - metabolism; toxicity
• ISSN: 1095-6433; 1531-4332
• DOI: 10.1016/j.cbpa.2012.04.016

High concentrations of sodium deoxycholate (NaDOC) produce toxic effects. This study explores the effect of a single high concentration of NaDOC on the intestinal Ca2+ 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 Ca2+ absorption was measured as well as the gene and protein expressions of molecules involved in the Ca2+ transcellular pathway. NaDOC inhibited the intestinal Ca2+ absorption, which was concentration dependent. Ca2+-ATPase mRNA decreased by the bile salt and the same occurred with the protein expression of Ca2+-ATPase, calbindin D28k and Na+/Ca2+ 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 Ca2+ 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 Ca2+ absorption through downregulation of proteins involved in the transcellular pathway, as a consequence of oxidative stress and mitochondria mediated apoptosis.