Biliary and systemic effects of fatty acid bile acid conjugates.

摘要

BACKGROUND: Fatty acid bile acid conjugates (FABACs) are novel synthetic molecules that solubilize cholesterol, prevent cholesterol crystal and gallstone formation, and dissolve pre-existing gallstones in mice. They are thus potential agents for gallstone prevention and treatment. The available knowledge concerning their biliary, systemic or possible toxic effects is, however, incomplete. AIM: To obtain information regarding biliary and systemic effects of FABACs. METHODS: Hamsters, rats and mice were administered C20-FABAC intragastrically, and serum and bile chemistries, organ histology, animal wellbeing, and survival were monitored. RESULTS: FABAC feeding (150 mg/kg/day) caused no adverse effects in any of the animal species studied. FABAC did not influence biliary cholesterol, phospholipid, or bile-salt concentrations in mice. In hamsters, biliary cholesterol concentration decreased slightly, but effects on phospholipids and bile salts were inconsistent. In some mouse strains, FABAC supplementationincreased transaminases slightly. In hamsters and rats, transaminases were mainly unaffected or even decreased. Serum alkaline phosphatase, creatinine, albumin and glucose were generally unaffected by FABAC feeding. No gross or histopathological differences between controls and FABAC-fed animals were noted in any of the organs investigated. CONCLUSIONS: C20-FABAC given at a pharmacological dose is safe and devoid of any significant toxic effects in three different animal species.