COX-2 inhibition attenuates lung injury induced by skeletal muscle ischemia reperfusion in rats

Background: Skeletal muscle ischemia reperfusion accounts for high morbidity and mortality, and cyclooxygenase (COX)-2 is implicated in causing muscle damage. Downregulation of aquaporin-1 (AQP-1) transmembrane protein is implicated in skeletal muscle ischemia reperfusion induced remote lung injury. The expression of COX-2 in lung tissue and the effect of COX-2 inhibition on AQP-1 expression and lung injury during skeletal muscle ischemia reperfusion are not known. We investigated the role of COX-2 in lung injury induced by skeletal muscle ischemia reperfusion in rats and evaluated the effects of NS-398, a specific COX-2 inhibitor. Methods: Twenty-four Sprague Dawley rats were randomized into 4 groups: sham group (SM group), sham + NS-398 group (SN group), ischemia reperfusion group (IR group) and ischemia reperfusion + NS-398 group (IN group). Rats in the IR and IN groups were subjected to 3 h of bilateral ischemia followed by 6 h of re perfusion in hindlimbs, and intravenous NS-398 8 mg/kg was administered in the IN group. In the SM and SN groups, rubber bands were in place without inflation. At the end of reperfusion, myeloperoxidase (MPO) activity, COX-2 and AQP-1 protein expression in lung tissue, PGE(2) metabolite (PGEM), tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta levels in bronchoalveolar lavage (BAL) fluid were assessed. Histological changes in lung and muscle tissues and wet/dry (W/D) ratio were also evaluated. Results: MPO activity, COX-2 expression, W/D ratio in lung tissue, and PGEM, INF-alpha and IL-1 beta levels in BAL fluid were significantly increased, while AQP-1 protein expression downregulated in the IR group as compared to that in the SM group (P < 0.05). These changes were remarkably mitigated in the IN group (P < 0.05). NS-398 treatment also alleviated histological signs of lung and skeletal muscle injury. Conclusion: COX-2 protein expression was upregulated in lung tissue in response to skeletal muscle ischemia re perfusion. COX-2 inhibition may modulate pulmonary AQP-1 expression and attenuate lung injury. (C) 2015 Elsevier B.V. All rights reserved.