Effects of 16,16-Dimethyl Prostaglandin E2 and Cholesterol on Biliary Mucous Glycoprotein and Gallstone Formation in Guinea Pigs

Chang, Jae Nam; Lee, Jin Woo; Kim, In Han; Kim, Sun Hoo; Jang, Dong Seob; Kwon, Kye Sook; Choi, Won; Lee, Don Haeng; Cho, Hyeon Geun; Kim, Pum Soo; Kim, Hyung Gil; Shin, Yong Woon; Kim, Young Soo

Abstract

BACKGROUND/AIMS: Prostaglandins is proposed to be responsible for gallstone formation in the animal models by hypersecretion of mucus in the gallbladder. This study was performed to determine the effect of 16,16-dimethyl prostaglandin E2 (dmPGE2) and cholesterol on mucous glycoprotein secretion of gallbladder in guinea pig.
METHODS
The prostaglandin was administered intraperitoneally to 30 guinea pigs fed with normal chow for 5 weeks at daily doses of 0 (controls), 15, 30 microgram/kg (n=10 at each dose). There was another group (10 animals) fed with chow containing 1% cholesterol and 0.5% cholic acid and administered no dmPGE2.
RESULTS
The concentration of biliary mucous glycoprotein was significantly higher in the animals fed with chow containing 1% cholesterol and the animals treated with dmPGE2 than in the control animals (p<0.05). The animals treated with dmPGE2 formed pigment gallstones, and the incidence was dose-dependent (p<0.001). All animals fed with a cholesterol-rich diet also formed pigment gallstones. Infrared spectometry showed that the pigment gallstones contained calcium phosphate and calcium bilirubinate as major components.
CONCLUSIONS
These results suggest that exogenous prostaglandin E2 increases concentration of mucous glycoprotein in the gallbladder bile and results in pigment gallstone formation through the mechanism similar to that of cholesterol-promoted gallstone formation.