Cytoprotective effects of taurocholic acid feeding on the biliary tree after adrenergic denervation of the liver.
BACKGROUND
Cholangiopathies impair the balance between proliferation and apoptosis of cholangiocytes leading to the disappearance of bile ducts and liver failure. Taurocholic acid (TC) is essential for cholangiocyte proliferative and functional response to cholestasis. Bile acids and neurotransmitters co-operatively regulate the biological response of the biliary epithelium to cholestasis. Adrenergic denervation of the liver during cholestasis results in the damage of bile ducts.


OBJECTIVE
To verify whether TC feeding prevents the damage of the biliary tree induced by adrenergic denervation in the course of cholestasis.


METHODS
Rats subjected to bile duct ligation (BDL) and to adrenergic denervation were fed a TC-enriched diet, in the absence or presence of daily administration of the phosphatidyl-inositol-3-kinase (PI3K) inhibitor wortmannin for 1 week.


RESULTS
TC prevented the induction of cholangiocyte apoptosis induced by adrenergic denervation. TC also restored cholangiocyte proliferation and functional activity, reduced after adrenergic denervation. TC prevented AKT dephosphorylation induced by adrenergic denervation. The cytoprotective effects of TC were abolished by the simultaneous administration of wortmannin.


CONCLUSIONS
TC administration prevents the damage of the biliary tree induced by the adrenergic denervation of the liver. These novel findings open novel perspectives in the understanding of the potential of bile acids especially in post-transplant liver disease.
Marzioni
Marco
M
Department of Gastroenterology, Università Politecnica delle Marche, Ancona, Italy. marco.marzioni@tele2.it
Ueno
Yoshiyuki
Y
Glaser
Shannon
S
Francis
Heather
H
Benedetti
Antonio
A
Alvaro
Domenico
D
Venter
Juliet
J
Fava
Giammarco
G
Alpini
Gianfranco
G
D018663:Adrenergic Agents; D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001659:Biliary Tract / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002779:Cholestasis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D003714:Denervation; D008099:Liver / Q000294:innervation*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020011:Protective Agents / Q000008:administration & dosage; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000077191:Wortmannin
D018663:Adrenergic Agents; D000730:Androstadienes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020011:Protective Agents; D013656:Taurocholic Acid; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin