Evidence for oxidative stress in the gall bladder mucosa of gall stone patients.

BACKGROUND: There is considerable evidence indicating that gall stone patients have altered gall bladder functions with respect to secretion and absorption and inflammation in mucus membrane when compared with gall stone free subjects. Increased levels of accelerated generation of reactive oxygen species and toxic degradative products of lipid peroxidation have been reported in the plasma of individuals with gall stones. The purpose of this study is to find out whether oxidative stress in mucosa plays any role in the pathogenesis of gall stone diseases. Levels of lipid peroxides, lipid hydroperoxides (LPH) and conjugated dienes were assessed in gall bladder mucosal scrapings obtained from 30 gall stone patients undergone cholecystectomy. Antioxidant enzymes such as catalase (EC 1.11.1.6), superoxidedismutase (EC 1.15.1.1), glutathione peroxidase (EC 1.11.1.9), glutathione transferase (EC 2.5.1.18) and glutathione reductase (EC 1.6.4.2) were assessed. The activity levels of alkaline phosphatase (EC 3.1.3.1), adenosine triphosphatase and protease (EC 3.4.24.11) were also assessed and data compared with identical data collected from 15 gall stone free subjects and 10 post-mortem cases. Gall stone patients had significantly higher levels of conjugated dienes, LPH and thiobarbituric acid reacting substances in their gall bladder mucosa. Lower levels of glutathione and glutathione related enzymes, catalase and superoxide dismutase were observed in those patients when compared to gall stone free subjects. The activities of functional enzymes in mucosa such as alkaline phosphatase, Na(+)-K+ (EC 3.6.1.3) and Ca2+ (EC 3.6.1.2) adenosine triphosphatase showed significant decreases. Histopathological observation showed lipid accumulation, dilated blood vessels, necrotic and fibrotic changes and inflammation in the gall bladder mucosa of gall stone patients. The data show that gall stone patients have a high level of oxidative stress in the gall bladder mucosa, a finding that may be related to a decreased activity of functional enzymes in mucosal cells. Such a condition might result in an altered gall bladder absorption and secretion of bile components such as mucins and glycoproteins. The resultant increased risk of bile saturation would further contribute to the progress of gall stone formation.