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Protective effects of glycoursodeoxycholic acid in Barrett's esophagus cells.

Abstract：

:Barrett's esophagus (BE) is a premalignant condition associated with the development of esophageal adenocarcinoma (EAC). Previous studies have implicated hydrophobic bile acids and gastric acid in BE and EAC pathogenesis. In this study, we tested the hypothesis that DNA damage, cytotoxicity and oxidative stress induced by bile acids and gastric acid can be attenuated by the cytoprotective, hydrophilic bile acid glycoursodeoxycholic acid (GUDCA). Non-dysplastic BE cells were exposed for 10 min to pH 4 and/or bile acid cocktail or to pH 4 and a modified cocktail consisting of a mixture of bile acids and GUDCA. DNA damage was evaluated by the comet assay; cell viability and proliferation were measured by trypan blue staining and the MTS assay; reactive oxygen species (ROS) were measured using hydroethidium staining; oxidative DNA/RNA damage was detected by immunostaining with antibody against 8-OH-dG; thiol levels were measured by 5-chloromethylfluorescein diacetate (CMFDA) staining; and the expression of antioxidant proteins was evaluated by western blotting. DNA damage and oxidative stress were significantly increased, while thiol levels were decreased in BE cells treated with pH 4 and bile acid cocktail compared with cells treated with pH 4 alone or untreated cells. Bile acids and low pH also significantly decreased cell proliferation. Expression of the antioxidant enzymes, MnSOD and CuZnSOD, was elevated in the cells treated with bile acids and low pH. When GUDCA was included in the medium, all these effects of pH 4 and bile acids were markedly reduced. In conclusion, treatment of BE cells with acidified medium and a bile acid cocktail at physiologically relevant concentrations induces DNA damage, cytotoxicity, and ROS. The cytoprotective bile acid, GUDCA, inhibits these deleterious effects by inhibiting oxidative stress.

journal_name

Dis Esophagus

journal_title

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus

authors

Goldman A,Condon A,Adler E,Minnella M,Bernstein C,Bernstein H,Dvorak K

doi

10.1111/j.1442-2050.2009.00993.x

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

83-93

issue

eissn

1120-8694

issn

1442-2050

pii

DES993

journal_volume

pub_type

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Protective effects of glycoursodeoxycholic acid in Barrett's esophagus cells.