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

Abstract

This study was performed to determine the effect of 16,16-dimethyl prostaglandin E₂ (dmPGE₂) on mucous glycoprotein secretion by the guinea pig gallbladder. The prostaglandin was given intra-peritoneally for 4 weeks at daily doses of 0 (controls), 10, 20, or 30 μg/kg body weight (n = 18 at each dose). These 72 animals were fed normal chow. A 5th group of 18 animals received chow containing 1% cholesterol and 0.5% cholic acid, and no dmPGE₂. There were statistically significant increases in the concentrations in gallbladder bile of mucous glycoprotein in the animals fed cholesterol and those treated with dmPGE₂, as compared with the controls. Moreover, the animals treated with dmPGE₂ formed black-pigmented gallstones, the incidence being dose-dependent, whereas all animals fed a cholesterol-rich diet formed amorphous yellow-brown gallstones. Even though these two types of gallstones appeared different on macroscopic examination, both consisted primarily of calcium phosphate and calcium bilirubinate. These results suggest that exogenous prostaglandin E₂ increases concentrations of mucous glycoprotein in the gallbladder bile, resulting in gallstone formation by a mechanism in part similar to the one whereby cholesterol loading promotes gallstone formation in this model.

Key Words:

• Gallstone
• guinea pig
• mucous glycoprotein
• prostaglandin