Gastrointestinal Disorders

TUDCA has been used to treat experimental gastrointestinal disorders. Inflammatory bowel diseases (IBDs) are immune-mediated disorders of the gastrointestinal tract that are chronically relapsing. ER stress mechanisms have been implicated in the pathogenesis of both acute and chronic conditions of intestinal inflammation. Chemical chaperones exhibit beneficial effects associated with ER stress mechanisms in the GI system by inhibiting the UPR. ER chaperone glucose regulated protein (GRP)78 releases three ER transmembrane proteins when unfolded proteins accumulate. This initiates the three branches of the UPR signaling
cascade. Research focusing on the regulation of classical UPR dependent genes like GRP78 and CHOP suggested that TUDCA could reduce ER stress and stabilize the UPR in intestinal epithelial cells. TUDCA was able to inhibit the activation of the early signaling steps in the three branches of UPR, preventing the formation and binding of activated transcription factors to the ERSE and UPRE elements of the GRP78 promoter for transcriptional activation. In this particular case, TUDCA acted as a potent chemical chaperone in the treatment of ER stress-associated diseases like IBD. In another study, researchers found that TUDCA reduced the damaging effects of taurodeoxycholic acid (TDCA) on fundus gastric mucosa. Bile acids, particularly deoxycholic acid, have been indicated to directly cause injury to the gastric mucosa. TDCA was studied in an amphibian model of gastric mucosa to assess the effects it has on inducing tissue damage, effects on electrical transepithelial parameters, acid secretion, and histology in absence or presence of TUDCA. TDCA caused a reduction in transepithelial potential difference and transepithelial resistance and a decrease in acid secretion from mucosal exposure. Neck cells were also affected by TDCA. TUDCA did not cause a significant change in electrical parameters and affected only oxyntic cells. A reduction in short circuit current and transepithelial resistance was observed with mucosal exposure to the combination of TUDCA and TDCA. The results suggested that TUDCA protected the gastric mucosa from the damaging effects of TDCA and that
TUDCA may play a role in treating gastritis associated with bile reflux.