Ursodeoxycholic acid and cholesterol induce enterohepatic cycling of bilirubin in rodents.
OBJECTIVE
Oral administration of ursodeoxycholic acid (UDCA) and cholesterol causes bile salt malabsorption; the former by competition for and the latter by down-regulation of ileal bile acid transporters. Because ileectomy in rats induces enterohepatic cycling of bilirubin, the hypothesis that dietary steroids might have the same effect was tested.


METHODS
Male inbred C57L/J mice and Sprague-Dawley rats were fed low doses of UDCA, chenodeoxycholic acid (CDCA), or cholesterol added to laboratory chow with simultaneous chow-fed controls. After 1 week (mice) or 2 weeks (rats), indices of bile salt malabsorption and enterohepatic cycling of bilirubin were measured, including bilirubin secretion rates into bile, serum and intestinal bilirubin and bile salt levels, and urobilinogen levels in cecum, large intestine, and feces.


RESULTS
Dietary UDCA and cholesterol, but not CDCA, significantly increased bilirubin secretion rates into bile. In UDCA-fed mice, gallbladder biles contained increased levels of bilirubin conjugates and unconjugated bilirubin, and in 60%, granules of amorphous calcium bilirubinate precipitated. Dietary cholesterol and bile acids, particularly UDCA, increased cecal bile salt levels, unconjugated bilirubin and urobilinogen concentrations, and decreased fecal bilirubin outputs, consistent with colonic absorption.


CONCLUSIONS
By causing bile salt malabsorption, dietary UDCA and cholesterol induce enterohepatic cycling of bilirubin.
Department of Medicine, Harvard Medical School, Gastroenterology Division, Brigham and Women's Hospital, and Harvard Digestive Diseases Center, Boston, Massachusetts, USA.
N
N
Méndez-Sánchez
M A
MA
Brink
B
B
Paigen
M C
MC
Carey
D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism; D001652:Bile Ducts / Q000502:physiology; D001663:Bilirubin / Q000097:blood / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004032:Diet; D004764:Enterohepatic Circulation / Q000187:drug effects / Q000502:physiology*; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D008286:Malabsorption Syndromes / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014558:Urobilinogen / Q000097:blood / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D002635:Chenodeoxycholic Acid; D014558:Urobilinogen; D014580:Ursodeoxycholic Acid; D001663:Bilirubin