Celecoxib modulates nitric oxide and reactive oxygen species in kidney ischemia/reperfusion injury and rat aorta model of hypoxia/reoxygenation

• COX-2 may affect the pathogenesis of renal failure following ischemia/reperfusion.
• Celecoxib improved oxidative stress parameters in ischemia/reperfusion injury.
• It equally increased NO bioavailability and decreased COX-2 levels in the kidney.
• COX-2/ROS/NO-cGMP interaction participates in the vasorelaxant effect of celecoxib.
• Celecoxib may act by more than one mechanism independent of COX-2 blockade.

ObjectiveThis study investigated the interaction between COX-2, NO and ROS after ischemia/reperfusion events in the kidney and vascular beds.Materials and methodsKidney IRI model in male Sprague–Dawley rats was used and various biochemical and histopathological parameters were examined. The isolated rat aortic rings served as model for hypoxia/reoxygenation.ResultsCelecoxib reduced serum creatinine and urea and kidney malonaldehyde levels, increased kidney superoxide dismutase activity and reduced glutathione level and histopathological scores at 24 and 48 h after reperfusion compared to IRI group. This was associated with a significant increase in NO level to 0.70 ± 0.03 nmol/mg protein compared to 0.37 ± 0.01 nmol/mg protein for IRI group. Unexpectedly, celecoxib reduced COX-2 expression in the kidney. Celecoxib reversed the effect of hypoxia–reoxygenation on ACh and SNP-induced relaxation in aortic rings but failed to potentiate the SNP relaxations in the control rings. Hypoxia–reoxygenation significantly impaired celecoxib’s relaxation of aorta (12.69 ± 2.69% vs. 35.84  ± 0.84%) which was significantly inhibited in presence of L-NAME.ConclusionsCelecoxib beneficially affects the outcome of renal IRI by lowering the expression of COX-2 and hence reducing oxidative stress and increasing the bioavailability of NO. Direct interaction between celecoxib and NO in associated vascular beds may also be a contributing mechanism.

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