CONICET | Buscador de Institutos y Recursos Humanos

The intestinal Ca2+ absorption is inhibited by sodium deoxycholate (NaDOC) and is increased by ursodeoxycholic acid (UDCA). In this work, we studied the effect of both bile acids on the mitochondrial dynamics, redox state and energy metabolism of intestine. Adult male Wistar rats were used: 1) controls, 2) NaDOC treated, 3) UDCA treated and 4) NaDOC + UDCA treated. Mitochondria were isolated from the duodenum of each group of animals by differential centrifugation. Spectrophotometric methods were used to quantify the activities of Krebs cycle oxidoreductases, complexes from electron transport chain (ETC) and enzymes of the antioxidant system. Gene expressions of Mfn-2, Drp-1 (mitochondrial dynamics proteins) and Pgc-1alfa (protein of mitochondrial biogenesis) were determined by RT-PCR. Glutathione (GSH) content, superoxide anion levels (˙O2-) and protein carbonyl content were also assayed. Results were analyzed by one-way ANOVA and Bonferroni post hoc test. NaDOC decreased the total GSH content and inhibited the activities of the malate dehydrogenase (MDH), isocitrate dehydrogenase (ICDH), complex III (ETC) and the Pgc-1 alfa gene expression. The combined treatment blocked the inhibitory effects produced by NaDOC. The activity of SOD and the contents of superoxide anion (.O2-) and protein carbonyls were increased by NaDOC, effects that were avoided by UDCA. The activities of ICDH and complex II (ETC) were increased by UDCA alone. In conclusion, the combined treatment avoids the oxidative stress triggered by NaDOC and blocks the inhibitory effect of NaDOC on the enzymatic activities from the Krebs cycle, the complex III (ETC) and the mitochondrial biogenesis. The stimulatory effect of UDCA on the intestinal Ca2+ absorption would be through an increase in the mitochondrial energy metabolism produced by bile acid.