Study of the effect of Bucillamine on the early and late phase of hepatic ischaemia reperfusion injury.
Doctoral thesis, UCL (University College London).
Ischaemia of the liver followed by reperfusion results in endothelial and parenchymal injury through a complex cascade of events. This often occurs in human liver transplantation as well as with major liver resections and is referred to as Ischaemia Reperfusion (IR) Injury. Bucillamine is a low molecular weight thiol antioxidant that is capable of rapidly entering cells. This thesis evaluates the effect of Bucillamine on both the early and late phases of liver warm IR injury with the hypothesis that beneficial effects are induced could be due to its action as a free radical scavenger. The drug was evaluated in an in vivo lobar liver ischemia reperfusion model as previously described. Male Sprague –Dawley rats were subjected to 45 mins of partial hepatic (70 %) ischaemia followed by 3 hrs of reperfusion to investigate the early phase of hepatic IR and 24 hrs of reperfusion to study the late phase of hepatic IR. Changes to the microcirculation, leucocyte adherence and apoptosis were assessed by intra-vital microscopy. Hepatocellular injury was assessed by standard liver function tests. Expression of pro and antiapoptotic gene expression was studied by RT-PCR. Oxidative stress was assessed by measuring plasma and hepatic F2 isoprostane levels and tissue glutathione levels. Cytokine response was assessed by measuring serum CINC-1 levels. Bucillamine improved liver sinusoidal perfusion, reduced leukocyte adherence and apoptosis in both the early and late phases of IR injury. Hepatocellular injury was reduced. There was no difference in the level of tissue glutathione or tissue and plasma F2 isoprostane levels. This study shows that the hepato protective effect of Bucillamine in warm Liver ischemia reperfusion injury is not by direct replenishment of Glutathione level; however, it is through decreased neutrophil activation and recruitment. A clinical trial could hence be undertaken in the future to study its efficacy.
|Title:||Study of the effect of Bucillamine on the early and late phase of hepatic ischaemia reperfusion injury.|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of) > Research Department of General Surgery|
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