Effects of molsidomine and lexipafant in hepatic ischaemia-reperfusion injury

Purpose: 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 mate Sprague-Dawley rats (200-225 g) were divided into five groups each containing 10 rats; group SO: Sham operation group; group 1: hepatic ischaemia group; group IR: ischaernia-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 1, 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 1 (P = 0.009 and 0.0035, respectively). The liver damage scores of groups M and L were significantly tower than that of group IR (P < 0.001 for both M and L). Mean MDA levels of groups 1 and IR were significantly higher than those of group SO (P < 0.001). Administrations of molsidomine and lexipafant prior to ischaernia-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. Conclusion: 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. ((C))2003 Elsevier Ltd. All rights reserved.