Effects of LTB4 receptor antagonist on myonephropathic metabolic syndrome: an experimental study

The aims of this study were to determine the involvement of leukocytes in reperfusion injury following acute arterial occlusion and to evaluate the effect of the leukotriene B4 (LTB4), which is a chemical mediator of inflammation, receptor antagonist. We examined the usefulness of LTB4 receptor antagonist, ONO-4057, as a preventative drug for myonephropathic metabolic syndrome (MNMS). The experimental leg ischemic model was developed using Wistar strain rats. The rats were divided into 4 groups. In Group R3, the infra-renal abdominal aorta was clamped for 3 hrs and the right femoral muscle tissue was cut to block the development of a collateral artery. In Group R6, the infra-renal abdominal aorta was clamped for 6 hrs and the right femoral muscle tissue was cut. In Group C, the controls, there was no clamping of the abdominal aorta and the right femoral muscle tissue was cut. In Group M, the medicated group, rats were pretreated with an LTB4 receptor antagonist, ONO-4057, just before reperfusion. Blood serum interleukin-1 (IL-1), interleukin-8 (IL-8), creatine phosphokinase (CPK), and aldolase were measured and compared in each of those 4 groups. We also examined the intercellular adhesion molecule-1 (ICAM-1) expression in various organs (liver, heart and kidney) by immunohistochemistry. We found that IL-1 beta levels were low in all groups. CPK, aldolase and IL-8 levels after reperfusion in Group R6 significantly high compared with the levels in Group C (P < 0.03 about CPK, P < 0.05 about aldolase, and P < 0.05 about IL-8). The levels of CPK, aldolase, and IL-8 in Group M were significantly lower than those in Group R6 (P < 0.02 about CPK, P < 0.04 about aldolase, and P < 0.03 about IL-8). We determined immunohistochemically that the expression of ICAM-1 was positive on endothelial cells at the coronary artery and the small vein in Group R6 and that the expression of ICAM-1 was negative on endothelial cells in Group C. Those data suggested that ICAM-1 may play an important role in the progression of reperfusion injury, and the adhesion of neutrophilic leukocytes on endothelial cells may play a significant role in MNMS. LTB4 receptor antagonist may be useful for preventing reperfusion injury following acute aortic occlusion.