The present study was undertaken to define the relationship between calcium metabolism and bile acid composition in animal models of diet induced cholesterol and pigment gallstones. Groups of prairie dogs were fed either a control non-lithogenic chow (N = 12), a 1.2% cholesterol enriched chow (N = 6, XOL) for two weeks, or a high carbohydrate diet deficient in iron (N = 6, CHO-FeD), or a high carbohydrate diet with normal iron levels (N = 6, CHO) for eight weeks. Hepatic (HB) and gallbladder (GB) bile samples were analyzed for total calcium, cholesterol, phospholipids, total bile acids (TBA), and individual bile acid composition. In each of the four groups, TBA concentrations were essentially similar and taurine conjugates accounted for approximately 90% of TBA in HB bile and about 98% in GB bile. In the control group, cholic acid (CA) was the predominant bile acid and comprised 76% of TBA and chenodeoxycholic (CDCA) accounted for about 13% of the total. Feeding a diet rich in cholesterol caused a significant change in the relative concentrations of individual bile acids of hepatic bile--such that CA decreased significantly (p less than 0.001) while CDCA increased by 300% (p less than 0.001). The changes in secondary bile acids were insignificant. An identical shift in individual bile acid composition was noted in animals maintained on high carbohydrate diet, irrespective of iron content. Similar changes were observed in the GB in the experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)
The efficacy of lovastatin, an inhibitor of hepatic cholesterol synthesis in the prevention of cholesterol gallstone formation, was evaluated in the prairie dog model. Two groups of animals were maintained on either nonlithogenic or 1.2% cholesterol-enriched chow for 21 days. Seven of the animals in each group received lovastatin, and the remaining six received only distilled water. All of the cholesterol-fed/water-treated animals had crystals and 83% had gallstones, but none of the cholesterol-fed/lovastatin-treated animals had gallstones and only three had microscopic crystals. These data indicate that lovastatin inhibits cholesterol gallstone formation in a diet-induced model of gallstone disease.
Recent studies suggest that altered gallbladder absorptive function may be an important and previously unrecognized factor in the pathogenesis of experimentally induced gallstones. The present study was designed to define the specific changes in gallbladder epithelial ion transport that occur during mixed gallstone formation. Fifteen prairie dogs were fed either control or corn-alfalfa chow for six months. No control animals developed gallstones or crystals. Three of eight corn-alfalfa-fed animals had large black stones, and the remaining five had crystals ("pregallstone" group). Corn-alfalfa-fed animals had significant increases in gallbladder bile cholesterol, phospholipids, and calcium as compared to controls. Gallbladders were removed and mounted in a Ussing chamber for electrophysiologic and ion flux studies. Gallbladders from animals fed corn-alfalfa demonstrated significant decreases in short-circuit current and potential difference as compared to controls (P less than 0.05). 22Na and 36Cl were used to determine unidirectional ion fluxes. While net ion fluxes were similar in pregallstone animals and controls, stone-forming animals exhibited a significant decrease in net Na+ flux and a significant reversal in the direction of net Cl- flux (from secretion to absorption) as compared to controls (P less than 0.05). These data indicate that mixed gallstone formation is associated with alterations in gallbladder ion transport. The role of these changes in the pathogenesis of mixed gallstones remains to be determined.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.