Cyclooxygenase-2 inhibitor celecoxib in a rat model of hindlimb ischemia reperfusion

Abstract

Acute ischemia-reperfusion (IR) of the limbs initiates both local and systemic injuries by triggering a systemic inflammatory response. Cyclooxygenase-2 (COX-2), an endogenous inducible enzyme, rises in response to inflammation. The aim of this work is to investigate the role of celecoxib, a selective COX-2 inhibitor, in abrogating remote organ dysfunction after hindlimb IR in rats by comparing it with a standard hemorrheologic drug (pentoxifylline). Rats were divided into 4 groups (n = 6 each), group I (sham control, received saline and was kept under anaesthetic for 7 h). Group II (IR, subjected to 1 h of hindlimb tourniquet ischemia and 6 h reperfusion). Group III and IV (pretreated with 200 mg/kg pentoxifylline or 10 mg/kg celecoxib, respectively, intragastrically for 7 days before IR induction). Administration of pentoxifylline or celecoxib produced significant reduction in SGPT, serum creatinine, malondialdehyde, and tumor necrosis factor-alpha and significant increase in blood pH, blood adenosine triphosphate, and reduced glutathione compared with the IR group (p < 0.05). There was no significant difference among the pretreated groups. Histopathologic findings of the IR lung showed alveolar destruction, inflammatory cells infiltration, mast cell degranulation, and necrosis of the gastrocnemius muscle fibres. These changes were attenuated in the pretreated groups. In conclusion, celecoxib can ameliorate IR induced remote organ injury to a similar extent as pentoxifylline through its antiinflammatory and antioxidant action.