Clinical Study of Ursodeoxycholic Acid in Barrett's Esophagus Patients

Prior research strongly implicates gastric acid and bile acids, two major components of the gastroesophageal refluxate, in the development of Barrett’s esophagus (BE) and its pathogenesis. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to protect esophageal cells against oxidative stress induced by cytotoxic bile acids. We conducted a pilot clinical study to evaluate the clinical activity of UDCA in patients with BE. Twenty-nine BE patients received UDCA treatment at a daily dose of 13–15 mg/kg/day for six months. The clinical activity of UDCA was assessed by evaluating changes in gastric bile acid composition and markers of oxidative DNA damage (8-hydroxydeoxyguanosine, 8OHdG), cell proliferation (Ki67), and apoptosis (cleaved caspase 3, CC3) in BE epithelium. The bile acid concentrations in gastric fluid were measured by liquid chromatography-mass spectrometry. At baseline, UDCA (sum of unchanged and glycine/taurine conjugates) accounted for 18.2% of total gastric bile acids. Post UDCA intervention, UDCA increased significantly to account for 93.39% of total gastric bile acids (p<0.0001). The expression of markers of oxidative DNA damage, cell proliferation, and apoptosis was assessed in the BE biopsies by immunohistochemistry. The selected tissue biomarkers were unchanged after 6 months of UDCA intervention. We conclude that high dose UDCA supplementation for six months resulted in favorable changes in gastric bile acid composition but did not modulate selected markers of oxidative DNA damage, cell proliferation, and apoptosis in the BE epithelium

Clinical Study of Ursodeoxycholic Acid in Barrett's Esophagus Patients

Prior research strongly implicates gastric acid and bile acids, two major components of the gastroesophageal refluxate, in the development of Barrett’s esophagus (BE) and its pathogenesis. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to protect esophageal cells against oxidative stress induced by cytotoxic bile acids. We conducted a pilot clinical study to evaluate the clinical activity of UDCA in patients with BE. Twenty-nine BE patients received UDCA treatment at a daily dose of 13–15 mg/kg/day for six months. The clinical activity of UDCA was assessed by evaluating changes in gastric bile acid composition and markers of oxidative DNA damage (8-hydroxydeoxyguanosine, 8OHdG), cell proliferation (Ki67), and apoptosis (cleaved caspase 3, CC3) in BE epithelium. The bile acid concentrations in gastric fluid were measured by liquid chromatography-mass spectrometry. At baseline, UDCA (sum of unchanged and glycine/taurine conjugates) accounted for 18.2% of total gastric bile acids. Post UDCA intervention, UDCA increased significantly to account for 93.39% of total gastric bile acids (p<0.0001). The expression of markers of oxidative DNA damage, cell proliferation, and apoptosis was assessed in the BE biopsies by immunohistochemistry. The selected tissue biomarkers were unchanged after 6 months of UDCA intervention. We conclude that high dose UDCA supplementation for six months resulted in favorable changes in gastric bile acid composition but did not modulate selected markers of oxidative DNA damage, cell proliferation, and apoptosis in the BE epithelium