Dissolution of cholesterol gallstones in mice by the oral administration of a fatty acid bile acid conjugate

Tuvia Gilat*, Alicia Leikin-Frenkel, Ilana Goldiner, Zamir Halpern, Fred M. Konikoff

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Gallstones, mostly cholesterol stones, affect some 15% of the population. Oral bile salts dissolve human cholesterol gallstones, but with low efficacy, and surgery remains the main therapeutic option. Fatty acid bile acid conjugates (FABACs) were shown to prevent formation of cholesterol gallstones in experimental animals. The aim of this study was to test whether these compounds could dissolve preexisting cholesterol gallstones via oral administration. Inbred, gallstone-susceptible C57J/L mice were given a lithogenic diet for 2 months, and the presence of gallstones was ascertained. The mice were then switched to a regular diet while part of them were given in addition C20-FABAC, by gavage, at a dose of 0.5 or 3 mg per animal per day. All mice tested had cholesterol gallstones after 2 months on the lithogenic diet. In study I, after 2 months on the regular diet, 3 of 4 (75%) of the controls had gallstones, whereas none of the 6 FABAC-fed animals (3 mg/d) had stones (P = .033). In study II, evaluating 2 FABAC doses, after 2 months on the regular diet, 8 of 8 (100%) of the controls had gallstones, which were found in 2 of 7 (28%) and 1 of 8 (12%) of the mice supplemented with 0.5 mg/d (P = .007) or 3 mg/d (P = .001) FABAC, respectively. On a molar basis, the dose of 0.5 mg FABAC is equivalent to 14 mg/kg/d of a bile acid. In conclusion, FABACs given orally can dissolve preexisting cholesterol gallstones in mice. This was accomplished with a dose of FABAC equivalent to the dose of bile acids used in human gallstone dissolution.

Original languageEnglish
Pages (from-to)597-600
Number of pages4
JournalHepatology
Volume35
Issue number3
DOIs
StatePublished - 2002

Fingerprint

Dive into the research topics of 'Dissolution of cholesterol gallstones in mice by the oral administration of a fatty acid bile acid conjugate'. Together they form a unique fingerprint.

Cite this