The protective mechanisms of defibrotide on liver ischaemia–reperfusion injury

Abstract

During some surgical interventions, temporary occlusion of the hepatic blood supply may cause ischaemia-reperfusion (I/R) injury and hepatic dysfunction. In this study the protective effect of defibrotide (DEF) was evaluated in a rat model of liver I/R injury. Four groups of rats were subjected to the following protocols: saline infusion without ischaemia, DEF infusion without ischaemia, DEF infusion with hepatic I/R, and saline infusion with hepatic I/R. After a midline laporatomy, liver ischaemia was induced by 45 min of portal occlusion. DEF 175 mg/kg(-1) was infused before ischaemia in 10 ml of saline. The same volume of saline was infused into the control animals. At the end of the 45-min reperfusion interval, the animals were sacrified. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities were determined in haemolysates, and malondialdehyde (MDA) level in the liver tissue was measured. Tissue MDA levels were significantly higher in the I/R plus saline group compared to the sham operation control groups (p < 0.01 and p < 0.05, respectively). Tissue MDA levels decreased in the DEF plus I/R group compared to the I/R plus saline group (p < 0.05), but DEF could not reduce tissue lipid peroxidation to the levels of the control sham operation groups. SOD and GSH-Px enzyme activities were significantly higher in DEF-treated animals than in the other groups (p < 0.05). These results suggest that DEF protects liver against I/R injury by increasing the antioxidant enzyme levels.

Protective effects of leflunomide against ischemia-reperfusion injury of the rat liver

“…Transient ischemia also cannot be avoided during hepatic transplantations. In addition, liver I/R injury plays important roles in severe infection, trauma, shock, and cardiorespiratory malfunction [32]. Temporary decrease of hepatic blood flow may produce critical reduction in hepatic perfusion with a risk of irreversible ischemic injury.…”

The grateful dead: damage‐associated molecular pattern molecules and reduction/oxidation regulate immunity

“…The major applications of ODNs have been as antisense constructs of 20–30 mers, CpG ODNs (212–215), and purified porcine gut‐derived ODNs. The latter natural product is composed of approximately 50–60 mers as defibrotide (216–221), a treatment for hepatic venocclusive disease (VOD), approved in Europe with pending approval in the United States. VOD is a lethal condition associated with intensive cancer chemotherapy alone (particularly busulfan‐ or melphalan‐containing regimens) and is observed in both autologous and allogeneic bone marrow transplantation settings.…”