Cell lines

The human colonic epithelial cell line HT-29

Preparation Method

The human CEC line HT-29 were treated with dilutions of Taurodeoxycholic acid (TDCA). and IL-8 secretion was analyzed in the supernatant 24 h after stimulation.NF-kappa B binding activity was analyzed with EMSA, RelA translocation with immunofluorescence, and RelA-phosphorylation with Western blot analysis.

Reaction Conditions

1,500 μM Taurodeoxycholic acid for 24h.

Applications

Taurodeoxycholic acid induced IL-8 gene expression correlated with enhanced RelA phosphorylation, which was blocked by Ad5dnIKK beta.Taurodeoxycholic acid primarily induced IL-8 gene expression through RelA phosphorylation.

Animal models

C57Bl/6J mice

Preparation Method

Mice were fed a liquid diet with or without Taurodeoxycholic acid supplementation. After 6 days, the mice were injected with LPS (10mg/kg) to induce intestinal injury. Specimens were obtained 24 hours later and evaluated for intestinal apoptosis, crypt proliferation, and villus length. A separate cohort of animals were injected with LPS (25mg/kg) and followed 7 days for survival.

Dosage form

50mg/kg/day Taurodeoxycholic acid, oral gavage

Applications

Mice whose diet was supplemented with Taurodeoxycholic acid had significantly increased survival. After LPS-induced injury, mice supplemented with Taurodeoxycholic acid showed decreased intestinal apoptosis by both H&E and caspase-3. Dietary taurodeoxycholic acid supplementation alleviates mucosal damage and improves survival after LPS-induced intestinal injury. Taurodeoxycholic acid is protective of the intestinal mucosa by increasing resistance to injury-induced apoptosis, stimulating enterocyte proliferation and increasing villus length.

Taurodeoxycholic acid (TDCA) is one of the Bile salts, are normally found within the intestinal lumen. The primary function of bile salts is to aid in the absorption of lipids and lipid-soluble vitamins. However, recent studies have shown that bile salts have other biologic effects independent of their role in digestion^[1].

Several effects of bile acids (BAs) on colonic epithelial cells (CECs) have been described, including induction of proliferation and apoptosis. Taurodeoxycholic acid (TDCA) is capable of inducing classic NF-κB activation in hepatoma cells, and induced IL-8 expression in a dose- and time-dependent manner. that there seems to be a classical NF-κB-dependent and an independent pathway in BA-induced IL-8 expression in CECs^[2].

The bile salt taurodeoxycholic acid (TDCA) has been associated with increased growth of esophageal mucosa in a rabbit explant model. Taurodeoxycholic acid increased gallbladder eicosanoid release in a dose-related manner with 6-keto-PGF1 alpha and PGE2 release 10-fold higher than TXB2.These findings suggest that the increased release of gallbladder PGI2 and PGE2 described in animal models of cholecystitis may, in part, be related to increased gallbladder bile levels of taurodeoxycholic acid^[3].

References:
[1].Perrone EE, Chen C, et al. Warner BW, Sun CC, Alaish SM, Strauch ED. Dietary bile acid supplementation improves intestinal integrity and survival in a murine model. J Pediatr Surg. 2010 Jun;45(6):1256-65.
[2]. Mühlbauer M, Allard B, et al. Differential effects of deoxycholic acid and taurodeoxycholic acid on NF-kappa B signal transduction and IL-8 gene expression in colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2004 Jun;286(6):G1000-8.
[3]. Myers SI, Riva A, et al. Taurodeoxycholic acid stimulates rabbit gallbladder eicosanoid release. Prostaglandins Leukot Essent Fatty Acids. 1995 Jan;52(1):35-9.