Bucillamine improves hepatic microcirculation and reduces hepatocellular injury after liver warm ischaemia-reperfusion injury

HPB (Oxford). 2009 May;11(3):264-73. doi: 10.1111/j.1477-2574.2009.00054.x.

Abstract

Background: Liver transplantation and resection surgery involve a period of ischaemia and reperfusion to the liver which initiates an inflammatory cascade resulting in liver and remote organ injury. Bucillamine is a low-molecular-weight thiol antioxidant that is capable of rapidly entering cells.

Methods: The effect of bucillamine was studied in a rat model of liver ischaemia-reperfusion injury with 45 min of partial (70%) liver ischaemia and at 3 and 24 h of reperfusion. Controls included ischaemia-reperfusion (I/R) only, sham and bucillamine alone (without ischaemia reperfusion). Liver injury was assessed by serum transaminases (AST and ALT). Sinusoidal blood flow and hepatocyte apoptosis were measured using intravital microscopy (IVM).

Results: The hepatocellular injury of I/R produced a markedly elevated serum AST which was reduced with bucillamine (2072.5 +/- 511.79 vs. 932 +/- 200.8, P < 0.05) at 3 h reperfusion. Bucillamine treatment with I/R also increased parenchymal blood flow [red blood cell (RBC) velocity 242.66 +/- 16.86 vs. 181.11 +/- 17.59, at the end of 3 h of reperfusion) and reduced hepatocyte necrosis/apoptosis at 3 h as well as 24 h (P > 0.001).

Conclusion: Bucillamine reduces the hepatocellular injury of liver ischaemia reperfusion and improves parenchymal perfusion.

Keywords: Bucillamine; antioxidants; intravital microscopy; liver ischaemia-reperfusion injury.