Dihydrocholesterol-induced gallstones in the rabbit: evidence that bile acids cause gallbladder epithelial injury

Rabbits fed a diet containing 0.75% dihydrocholesterol for 7 days develop bile acid allodeoxycholic (ADCA) and deoxycholic acid (DCA) stones in the gallbladder. In this model, inflammatory changes in the gallbladder mucosa are often observed even before stones are formed. Within 3 days of the lithogenic diet, abnormalities of platelet function were detectable. Platelet aggregation upon addition of adenosine diphosphate (ADP) was impaired. At the same time the red cells became crenated and developed thorny spicules (echinocytes). This morphological changes was associated with intracellular dehydration and excessive loss of potassium. These changes coincided with a rise in serum ADCA and DCA and preceded a slow rise in serum cholesterol. In vitro incubation studies also suggested that the bile acids had probably caused membrane injury to the platelets and red cells. It is concluded that changes in the bile ADCA and DCA probably induce gallbladder epithelial injury in this model of experimental cholelithiasis.