Study Of Effects Of Rofecoxib On The Arachidonic Acid Metabolites In Mice With Foot Sweelling

Objective:Rofecoxib is a specific COX-2inhibitor which has an effect of pain relief and anti-inflammation, but there was an increased relative risk of occurrence of cardiovascular events in patients who keep taking rofecoxib, such as heart attacks and strokes. It has attracted more attentions to the researches of the mechanism of cardiovascular risk induced by rofecoxib and drugs of the same kind, such as celecoxib. The present study was to analyze the effects of rofecoxib on the plasma arachidonic acid(AA) metabolites so as to discuss the possible mechanisms of rofecoxib to cardiovascular risk and to provide a reference for clinical safe use of other similar drugs.Methods:Male C57mice were randomly assigned to control group,foot-swelling group, and rofecoxib group.. Feet thickness of mice was measured before disposal. For foot-swelling group and rofecoxib group,1%carageen glue was given by foot subcutaneous injection; for rofecoxib group, rofecoxib was injected introperitoneally at20mg/kg; for control group, normal saline was injected at corresponding timepoint.2hours later, feet thickness was measured and the blood and foot tissue were taken. tMorphology of foot tissue was observed; tumor necrosis factor-a(TNF-α) and metabolites of AA was detected respectively.Results:Under microscope the foot tissue of foot-swelling group showed infiltration of a large number of inflammatory cells and obvious tissue swelling, suggesting the inflammatory model by carageen glue was established. While the swelling of feet tissue was significantly inhibited in rofecoxib group. Moreover, compared with the foot-sweelling group, the content of6-keto-prostaglandin Flα(6-keto-PGF1α)、prostaglandin E2(PGE2) and11-hydroxy-eicosatetraenoic acid(11-HETE) in plasma of rofecoxib group was significantly lowered (p<0.01, p<0.05, p<0.05respectively). Compared with the control group, the plasma content of leukotriene B4(LTB4)、8-hydroxy-eicosatetraenoic acid(8-HETE)、12-hydroxy-eicosatetraenoic acid(12-HETE) and8,9-epoxyeicosatrienoic acid(8,9-EET) of rofecoxib group was also significantly lowered (p<0.01, p<0.01, p<0.05respectively)Conclusions:Rofecoxib sighificantly decreased the plasma content of AA metabolites, PGI2, PGE2,11-HETE,12-HETE and8,9-EET in mice with foot-sweelling, which may be the possible mechanism of cardiovascular risk induced by rofecoxib.