The protective mechanisms of defibrotide on liver ischaemia-reperfusion injury
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Date
2003
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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. © 2003 John Wiley & Sons, Ltd.
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Keywords
Animals , Glutathione Peroxidase , Liver , Male , Malondialdehyde , Polydeoxyribonucleotides , Rats , Reperfusion Injury , Superoxide Dismutase , Animalia , antioxidant , defibrotide , glutathione peroxidase , liver protective agent , malonaldehyde , sodium chloride , superoxide dismutase , animal experiment , animal model , animal tissue , article , blood vessel occlusion , controlled study , disease model , drug effect , drug infusion , drug mechanism , enzyme activity , enzyme assay , hemolysate , laparotomy , lipid peroxidation , liver injury , liver ischemia , liver level , liver protection , male , nonhuman , priority journal , quantitative analysis , rat , reperfusion injury