Ursodeoxycholic and deoxycholic acids: Differential effects on intestinal Ca2+ uptake, apoptosis and autophagy of rat intestine

• NaDOC decreases and UDCA increases Ca2+ uptake by mature enterocytes. NaDOC triggers and UDCA decreases the apoptosis.
• NO content and iNOS protein are enhanced by NaDOC, which is avoided by UDCA.
• Autophagy is produced by NaDOC, which is also prevented by UDCA.

The aim of this work was to study the effect of sodium deoxycholate (NaDOC) and ursodeoxycholic acid (UDCA) on Ca2+ uptake by enterocytes and the underlying mechanisms. Rats were divided into four groups: a) controls, b) treated with NaDOC, c) treated with UDCA d) treated with NaDOC and UDCA. Ca2+ uptake was studied in enterocytes with different degrees of maturation. Apoptosis, autophagy and NO content and iNOS protein expression were evaluated. NaDOC decreased and UDCA increased Ca2+ uptake only in mature enterocytes. The enhancement of protein expression of Fas, FasL, caspase-8 and caspase-3 activity by NaDOC indicates triggering of the apoptotic extrinsic pathway, which was blocked by UDCA. NO content and iNOS protein expression were enhanced by NaDOC, and avoided by UDCA. The increment of acidic vesicular organelles and LC3 II produced by NaDOC was also prevented by UDCA. In conclusion, the inhibitory effects of NaDOC on intestinal Ca2+ absorption occur by decreasing the Ca2+ uptake by mature enterocytes. NaDOC triggers apoptosis and autophagy, in part as a result of nitrosative stress. In contrast, UDCA increases the Ca2+ uptake by mature enterocytes, and in combination with NaDOC acts as an antiapoptotic and antiautophagic agent normalizing the transcellular Ca2+ pathway.