Administration of the selective cyclooxygenase (COX)-2 inhibitor etodolac prolongs cardiac allograft survival in a mouse model

Abstract

Etodolac, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug. COX-2 is a key factor in the progression of inflammation. Although inflammation is an essential pathologic feature of cardiac allograft rejection, the role of COX-2 in this process remains unclear. The aim of this study was to investigate the expression of COX and the effects of etodolac in a mouse cardiac allograft model. Balb/c mice (H-2d) were used as recipients and C57BL/6 (H-2b) mice as heart donors. Heart function was evaluated daily after transplantation by regular abdominal palpation of the heart and by laparotomy in cases where the beating became weak. Rejection was defined as total cessation of cardiac muscle contraction. COX-2 expression was analyzed by immunohistochemistry Cardiac isograft was well tolerated (>150 days, n=5), while non-treated cardiac allograft was rapidly rejected (mean 10.9±2.4, n=7). In the etodolac-treated cardiac allograft (10 mg/kg/day by hypodermic injection), survival was extended to 18.53±2.1 days (n=7). The necrotic area and the grade of COX-2 immunostaining were more significantly reduced in the etodolac-treated cardiac allograft than in the non-treated cardiac allograft at day 14. These results indicate that etodolac contributes to protection against rejection after heart transplantation. Etodolac could therefore be used to suppress graft rejection by means of its anti-inflammatory properties.