Ursodeoxycholate further increases bile-duct cell proliferative response induced by partial bile-duct ligation in rats.
BACKGROUND
Bile salts (BSs) stimulate cholangiocyte proliferation in vitro and in vivo in normal rats. In this study, we evaluated the effects of BS-enriched diets on cholangiocyte proliferative activity already triggered by partial bile-duct ligation (pBDL), a surgical model that induces mild cholestatic conditions, focusing our attention on ursodeoxycholate (UDC).


METHODS
Animals (n=45) were fed either a standard diet, or a 0.2% deoxycholate- or 0.2% UDC-enriched diet for 4 weeks. Then, in each group, ten animals underwent pBDL and five underwent sham operation. Serum and biliary BS levels, serum cholestasis and cytolysis indexes, as well as liver conventional histology, apoptosis and proliferative activity were evaluated 48 h after the operation.


RESULTS
Animals that underwent pBDL showed sustained proliferative response compared with sham-operated rats. BS-enriched diets did not influence cholangiocyte proliferation in sham-operated rats. However, significantly increased proliferation was observed in pBDL rats fed a UDC-enriched diet. The evaluation of humoral and histological parameters excluded the possibility that the increased proliferation induced by UDC-enriched diet could be related to concomitant liver cell damage.


CONCLUSIONS
A UDC-enriched diet is able to amplify the magnitude of the cholangiocyte hyperplastic process, which occurs by a stimulatory mechanism after partial bile-duct ligation.
Barone
Michele
M
Section of Gastroenterology, D.E.T.O., University of Bari, Italy.
Maiorano
Eugenio
E
Ladisa
Roberta
R
Pece
Antonia
A
Berloco
Pasquale
P
Strazzabosco
Mario
M
Caruso
Maria Lucia
ML
Valentini
Anna Maria
AM
Ierardi
Enzo
E
Di Leo
Alfredo
A
Francavilla
Antonio
A
D000284:Administration, Oral; D000818:Animals; D001652:Bile Ducts / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D002455:Cell Division / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000494:pharmacology*; D001651:Cholestasis, Extrahepatic; D002780:Cholestasis, Intrahepatic / Q000097:blood / Q000209:etiology / Q000473:pathology; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D004195:Disease Models, Animal; D008026:Ligation; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008111:Liver Function Tests; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D002756:Cholagogues and Choleretics; D018809:Proliferating Cell Nuclear Antigen; D003840:Deoxycholic Acid; D014580:Ursodeoxycholic Acid