1. The purpose of this study was to investigate the protective effects of
defibrotide, a single-stranded
polydeoxyribonucleotide, on ischaemia-
reperfusion injury to the liver using a rat model. 2. Ischaemia of the left and median lobes was created by total inflow occlusion for 30 min followed by 60 min of reperfusion. Hepatic injury was assessed by the release of liver
enzymes (
alanine transferase, ALT and lactic
dehydrogenase, LDH). Hepatic
oxidant stress was measured by
superoxide production, lipid peroxidation and
nitrite/
nitrate formation. Leukocyte-endothelium interaction and Kupffer cell mobilization were quantified by measuring hepatic
myeloperoxidase (MPO), polymorphonuclear leukocyte adherence to superior mesenteric artery (SMA) and immunostaining of Kupffer cell. 3.
Defibrotide treatment resulted in a significant inhibition of postreperfusion
superoxide generation, lipid peroxidation, serum ALT activity, serum LDH activity, MPO activity, serum
nitrite/
nitrate level, leukocyte adherence to SMA, and Kupffer cell mobilization, indicating a significant attenuation of hepatic dysfunction. 4. A significant correlation existed between liver ischaemia/reperfusion and hepatic injury, suggesting that liver ischaemia/
reperfusion injury is mediated predominantly by generation of
oxygen free radicals and mobilization of Kupffer cells. 5. We conclude that
defibrotide significantly protects the liver against liver ischaemia/
reperfusion injury by interfering with Kupffer cell mobilization and formation of
oxygen free radicals. This study provides strong evidence that
defibrotide has important beneficial effects on acute inflammatory tissue injury such as that occurring in the reperfusion of the ischaemic liver.