Effect of bile acids on ischemia-reperfusion liver injury.
We investigated whether stimulation of bile flow by taurocholic acid (TCA), ursodeoxycholic acid (UDCA) or its taurine conjugate (TUDCA) could protect the liver from ischemia-reperfusion injury. The isolated perfused rat liver model was used. In livers perfused without bile acids (n = 8), 60 min of ischemia induced a significant reduction in bile flow and in portal flow, together with a marked increase in LDH, AST and uric acid release in the perfusate. These alterations were maximal at the beginning of reperfusion. In livers perfused with TCA (n = 6), UDCA (n = 7) or TUDCA (n = 6), bile flow was significantly increased as compared to controls during the pre-ischemic phase, as well as during the reperfusion phase. However, no significant improvement was observed in any of the biochemical, hemodynamic or histologic parameters studied. The results show that stimulation of bile flow either by TCA, UDCA or TUDCA does not reduce ischemia-reperfusion liver injury. Furthermore, the results do not provide evidence for a cytoprotective effect of UDCA or TUDCA in this model of liver injury.
Chazouillères
O
O
INSERM U.181, Unité d'Hépatogastroentérologie, Hôpital Saint-Antoine, Paris, France.
Ballet
F
F
Legendre
C
C
Bonnefis
M T
MT
Rey
C
C
Chrétien
Y
Y
Poupon
R
R
D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology*; D007536:Isomerism; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000503:physiopathology*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D013656:Taurocholic Acid / Q000494:pharmacology*; D014527:Uric Acid / Q000032:analysis; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D014527:Uric Acid; D013655:Taurochenodeoxycholic Acid; D013656:Taurocholic Acid; C031655:ursodoxicoltaurine; D014580:Ursodeoxycholic Acid; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases