RESUMEN
BACKGROUND/AIMS: Although beneficial roles of hepatocyte growth factor (HGF) and its variants on several hepatic disorders have been reported, their effects on hepatic ischemia-reperfusion (IR) injury remain undetermined. We investigated the action of a deleted form of HGF (dHGF) on hepatic IR injury in rats. METHODS: dHGF or phosphate-buffered saline was continuously infused intravenously for 20 h prior to a 20-min occlusion of hepatic vessels. Samples were taken before and after IR, for measurement of serum dHGF and released enzymes, liver gamma-glutamylcysteinyl glycine (GSH) level, as well as histological and immunohistochemical examinations. RESULTS: After reperfusion, histological injury, as well as increase in the serum activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase-BB were significantly attenuated in the dHGF-treated rats. dHGF maintained a high GSH level and suppressed oxidative stress and intercellular adhesion molecule-1 (ICAM-1) expression on sinusoidal endothelial cells (SECs), on which c-Met was not detected. IR caused activation of c-Met expression, which was milder in the dHGF-treated group, in hepatocytes at the pericentral region. CONCLUSIONS: dHGF attenuated liver injury after IR. It also maintained a higher GSH level, depressed oxidative stress and inhibited ICAM-1 expression on c-Met negative SECs, suggesting a paracrine effect of dHGF.