Effects of molsidomine and lexipafant in hepatic ischaemia--reperfusion injury.
OBJECTIVE
The purpose of this study was to evaluate the effects of nitric oxide donor molsidomine and platelet-activating factor (PAF) antagonist lexipafant on the hepatic IR injury in rats.


METHODS
Fifty male Sprague-Dawley rats (200-225 g) were divided into five groups each containing 10 rats; group SO: Sham operation group; group I: hepatic ischaemia group; group IR: ischaemia-reperfusion (IR); group M: IR plus pretreatment with molsidomine; group L: IR plus pretreatment with lexipafant. Hepatic ischaemia and reperfusion, each were applied for 45 min. Hepatic specimens were obtained to determine the tissue levels of malondialdehyde (MDA) and histological changes. Blood samples were obtained by cardiac puncture for determination of alanine transaminase (ALT), aspartate transaminase (AST) and lactic dehydrogenase (LDH).


RESULTS
The liver damage scores of groups I, IR, M and L were significantly higher than that of group SO (P < 0.001). The liver damage scores of groups IR and M were significantly higher than that of group I (P = 0.009 and 0.0035, respectively). The liver damage scores of groups M and L were significantly lower than that of group IR (P < 0.001 for both M and L). Mean MDA levels of groups I and IR were significantly higher than those of group SO (P < 0.001). Administrations of molsidomine and lexipafant prior to ischaemia-reperfusion (IR) resulted in significant reduction of the MDA values (P < 0.001). A statistically significant (P < 0.001) decrease in the levels of AST, ALT and LDH was observed in groups M and L compared with group IR.


CONCLUSIONS
In conclusion, these observations suggest that pre-treatment with nitric oxide donor molsidomine and PAF antagonist lexipafant before the reperfusion period may be useful in preventing hepatic reperfusion injury.
Aldemir
Mustafa
M
Department of General Surgery, Faculty of Medicine, Dicle University, Diyarbakir 21280, Turkey. maldemir21@hotmail.com
Boşnak
Mehmet
M
Al
Behçet
B
Büyükbayram
Hüseyin
H
Taçyildiz
Ibrahim
I
D000818:Animals; D007093:Imidazoles / Q000627:therapeutic use*; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply*; D008297:Male; D008981:Molsidomine / Q000627:therapeutic use*; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
D007093:Imidazoles; D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D008981:Molsidomine; D007930:Leucine; C103289:lexipafant