The protective mechanisms of defibrotide on liver ischaemia-reperfusion injury.
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.
Aydemir
E O
EO
Department of Biochemistry and Clinical Biochemistry, Celal Bayar University School of Medicine, 45100 Manisa, Turkey. ece.onur@bayar.edu.tr
Var
A
A
Uyanik
B S
BS
Ilkgül
O
O
Aydede
H
H
Sakarya
A
A
D000818:Animals; D005979:Glutathione Peroxidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism
D011089:Polydeoxyribonucleotides; C036901:defibrotide; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase