title: Celecoxib modulates nitric oxide and reactive oxygen species in kidney ischemia/reperfusion injury and rat aorta model of hypoxia/reoxygenation.
abstract: 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.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Egypt. Electronic address: senbelamira@alexpharmacy.edu.eg.
authors.forename: A M
authors.initials: AM
authors.lastname: Senbel
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy and Drug Manufacturing, Pharos University, Egypt.
authors.forename: L
authors.initials: L
authors.lastname: AbdelMoneim
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Alexandria University, Egypt.
authors.forename: A G
authors.initials: AG
authors.lastname: Omar
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D000068579:Celecoxib; D015687:Cell Hypoxia; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D010100:Oxygen
keywords: Celexocib; Hypoxia/reoxygenation; Ischemia/reperfusion; Nitric oxide; Reactive oxygen species