Therapeutic and Chemopreventive Effects of Ursodeoxycholic Acid (UDCA): Potential Role in Patients with Barrett’s Esophagus

Abstract

Ursodeoxycholic Acid (UDCA) is widely used for the treatment of cholestatic liver
diseases. Major mechanisms of this action are protection of cholangiocytes against cytotoxicity
of hydrophobic bile acids, stimulation of hepatobiliary secretion, and protection of hepatocytes
against bile acid induced apoptosis. UDCA has also been shown to modulate mitochondrial
transmembrane potential and prevent increases in mitochondrial Reactive Oxygen Species
(ROS) production. Moreover, UDCA has been shown to have a chemopreventive role in mouse
models of colon cancer and in patients with primary sclerosing cholangitis and concomitant Inflammatory
Bowel Disease (IBD), low dose UDCA lowers the risk of IBD-associated colorectal
neoplasia. Our studies suggest that oral UDCA may protect against DNA damage induced by
hydrophobic bile acids such as Deoxycholic acid (DCA) in the metaplastic mucosa of patients
with Barrett’s esophagus. We have found that DCA induces carcinogenic DNA damage in Barrett’s
metaplasia. UDCA which counters the DNA damaging effects of DCA therefore might
have a role as a chemopreventive agent in Barrett’s metaplasia. Future clinical studies on the