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

OBJECTIVE

This study investigated the interaction between COX-2, NO and ROS after ischemia/reperfusion events in the kidney and vascular beds.

METHODS

Kidney 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.

RESULTS

Celecoxib 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.

CONCLUSIONS

Celecoxib 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.