Tauroursodeoxycholate ameliorates reperfusion injury after pig liver transplantation

Abstract

Reperfusion injury is a serious problem after clinical liver transplantation, often leading to dys-or even non-function of grafts. The present study was designed to determine whether the hydrophilic bile salt tauroursodeoxycholate (TUDC), known to be hepatoprotective in cholestatic liver disease, mitigates reperfusion injury in an in vivo pig liver transplantation model. Liver transplantation was performed in 12 pigs after a preservation time of 8 h. TUDC was administered to donor and recipient animals, and saline to controls. Blood was drawn at different time points for determination of liver enzymes. Bile samples were collected, and bile flow (BF), and bile salt secretion rate (BSSR) determined. Samples of liver tissue and bile ducts were taken for assessment by light and electron microscopy. Liver enzymes were significantly lower in the TUDC group. BF and BSSR were significantly higher. Microscopy revealed better preservation of bile duct architecture of the TUDCinfused animals. We can conclude that infusions of TUDC in pig livers ameliorate reperfusion injury in vivo. The molecular basis for this finding may be the membrane stabilizing effect of TUDC. Further studies are warranted to clarify its effect.

Neuroprotection by a Bile Acid in an Acute Stroke Model in the Rat

“…Oral administration of UDCA and TUDCA has been used clinically in the management of a variety of hepatic diseases associated with cholestatic syndromes, such as primary biliary cirrhosis (Beuers et al, 1998;Invernizzi et al, 1999). In addition, it has recently been reported that these molecules can also protect the liver during ischemic insult (Ono et al, 1995;Hertl et al, 1999;Falasca et al, 2000). The cytoprotective mechanism of UDCA and TUDCA results, in part, from their ability to inhibit apoptosis in hepatic cells by preventing mitochondrial depolarization and reactive oxygen species production (Rodrigues et al, 1998a,b).…”

Porcine alanine transaminase after liver allo‐and xenotransplantation

“…Several groups used pig‐to‐pig allotransplantation models to study the effect of different preservation solutions [4,5], cold and/or warm ischemic damage [6,7], and different medications on graft survival [8–11]. After WT pig liver allotransplantation, we could not find any report of increase in ALT; in the majority of reports, however, no mention was made of changes in ALT (although changes in AST were reported), suggesting to us that there was no change in ALT, and therefore, it was not considered worthy of reporting.…”

Addressing the Donor Liver Shortage with EX VIVO Machine Perfusion

“…By measuring creatine kinase and hyaluronic acid, both markers of endothelial damage that precede hepatocellular enzyme release [127,128], evaluation timeliness and specificity is improved, while better informing the treatment approach. Similarly, biliary endothelial damage, presently evaluated with alkaline phosphatase or gamma-glutamyl transpeptidase [129], and biliary function, assessed by total bilirubin production and bile acid content [119,130], are critical measurements for DCD organs, which are known to have high incident of biliary complications [131][132][133]. It is also important to perform this modeling directly in human livers to avoid species-dependent differences, particularly in biliary dysfunction which will adversely impact automation of any proposed treatment strategies [134,135].…”