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  • Title: Activated protein C prevents hepatic ischaemia-reperfusion injury in rats.
    Author: Kuriyama N, Isaji S, Hamada T, Kishiwada M, Ohsawa I, Usui M, Sakurai H, Tabata M, Suzuki K, Uemoto S.
    Journal: Liver Int; 2009 Feb; 29(2):299-307. PubMed ID: 18507760.
    Abstract:
    BACKGROUND: Hepatic ischaemia-reperfusion injury (IRI) is a serious complication of liver surgery, especially extended hepatectomy and liver transplantation. Activated protein C (APC), a potent anticoagulant serine protease, has been shown to have cell-protective properties by virtue of its anti-inflammatory and anti-apoptotic activities. METHODS: The present study was designed to examine the cytoprotective effects of APC in a 60-min warm-IRI rat model. RESULTS: Following a single intravenous injection of APC before reperfusion, APC exerted cytoprotective effects 4 h after reperfusion, as evidenced by: (i) decreased levels of transaminase and improved histological findings of IRI, (ii) reduced infiltration and activation of neutrophils, macrophages and T cells, (iii) reduced expression of tumour necrosis factor-alpha, (iv) reduced expression of P-selectin and intracellular adhesion molecule-1, (v) inhibited coagulation and attenuated sinusoidal endothelial cell injury, (vi) improved hepatic microcirculation and (vii) decreased transferase-mediated dUTP nick end-labelling-positive cells. These effects of APC were observed 4 h but not 24 h after reperfusion. However, multiple injections of APC after reperfusion significantly decreased the levels of transaminase and the activity of myeloperoxidase, and improved histological findings of IRI 24 h after reperfusion. CONCLUSION: These results suggest that APC is a promising therapeutic option for hepatic warm-IRI; however, multiple injections of APC are necessary to maintain its cell-protective action over the long term.
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