Yong Lee, Pavlos Jonthan, Jonathan Bower, Catharina Grulich, Jennifer Hollox, Sabin Scheetz
Abstract
Ischemia and reperfusion (I/R) are common clinical complications that lead to organ lesions following transplantation, hepatic surgery, and shock. Injury can exacerbate hepatic I/R conditions, influencing patient mortality. The pathogenesis of I/R injury remains unclear but involves various factors. Inflammatory responses occur immediately following reperfusion, peak in a few hours and gradually abate within a few days. Prominent features within these inflammatory processes consist of an increase in the influx of leukocytes including neutrophils, which can exacerbate the inflammatory condition. Observations suggest that neutrophil and platelet interaction could promote hepatic I/R injury. In addition, synthesis of endothelial cell adhesion molecules such as P-selectin, intercellular adhesion molecule 1 (ICAM-1) and E-selectin, which induce leukocyte adherence, occurs prominently during hepatic I/R. Soluble CD44 has also been found among leukocytes transmigrated into the endothelium and injured tissue, where it mediates cell/tissue recruitment and the promotion of inflammation. It is known that exposure to colchicine for 7 to 14 days prevents or attenuates reperfusion injury in various organs. At present, treatments for hepatic I/R injury remain less than satisfactory. As a result, the investigation of medicines that might prevent reperfusion injury in the clinical environment is required. In this study, colchicine, a natural extract with an anti-inflammatory constitution, was adopted to investigate its effects on the hepatic I/R injury in mice and its hepatoprotective mechanisms. Helpful information discovered could supply a potential clinical treatment strategy.
Keywords: Hepatic ischemia-reperfusion; Inflammatory response; Colchicine; Oxidants
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