Biliary and systemic effects of fatty acid bile acid conjugates.
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.


OBJECTIVE
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 supplementation increased 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.
Konikoff
Fred M
FM
Minerva Centre for Cholesterol Gallstones and Lipid Metabolism in the Liver, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. konikoff@post.tau.ac.il
Leikin-Frenkel
Alicia
A
Goldiner
Ilana
I
Michowitz
Moshe
M
Brezowski
Eli
E
Harats
Dror
D
Gilat
Tuvia
T
D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D019826:Cholic Acid / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D005227:Fatty Acids / Q000633:toxicity*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000187:drug effects; D013045:Species Specificity
D001786:Blood Glucose; D005227:Fatty Acids; D012709:Serum Albumin; D002784:Cholesterol; D003404:Creatinine; D019826:Cholic Acid