title: Effect of celecoxib and L-NAME on global ischemia-reperfusion injury in the rat hippocampus.
abstract: Transient global ischemia continues to be an important clinical problem with limited treatment options. The present study aimed to investigate the possible protective effects of celecoxib [a selective cyclooxygenase (COX-2) inhibitor] and N-omega-nitro-L-arginine methyl ester (L-NAME) [a nonselective nitric oxide synthase (NOS) inhibitor] against global ischemia-reperfusion (IR) induced biochemical and histological alterations in the rat hippocampus. Global ischemia was induced by bilateral clamping of the common carotid arteries for 60 minutes. Hippocampal cysteinyl aspartate-specific protease-3 (caspase-3) activity, nitrite/nitrate contents (NOX), as well as COX-2 immunoreactivity in the hippocampal Cornu Ammonis 1 (CA1) subregion were dramatically increased 24 hours after global ischemia. After 72-hour of reperfusion, ischemia induced a selective, extensive neuronal loss in the hippocampus CA1 subregion. Celecoxib (3 and 5 mg/kg, intraperitoneally; i.p.), administered 30 minutes before ischemia and at 6, 12, and 22 hours of 24-hour reperfusion, caused significant reductions in hippocampal caspase-3 activity as well as the number of COX-2 immunoreactive (COX-2 ir) neurons in the CA1 subregion. Further, celecoxib (3 or 5 mg/kg, i.p.), administered 30 minutes before ischemia and at 6, 12, 22, and 48 hours of 72-hour reperfusion, provided a notable histological protection of hippocampal CA1 neurons. Meanwhile, L-NAME (3 mg/kg, i.p.), administered twice (immediately after ischemia and 45 minutes after starting the reperfusion period), effectively reduced the elevated NOX level, decreased hippocampal caspase-3 activity and COX-2 immumoreactivity, and ameliorated ischemia-induced damage in the hippocampal CA1 subregion. The present study indicates that celecoxib and L-NAME might be neuroprotective agents of potential benefit in the treatment of cerebral ischemia.
authors.affiliation: Pharmacology and Toxicology Department, Faculty of Pharmacy, October 6 University, Sixth of October, Egypt.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Abd El-Aal
authors.forename: Maha M
authors.initials: MM
authors.lastname: El-Sawalhi
authors.forename: Mona
authors.initials: M
authors.lastname: Seif-El-Nasr
authors.forename: Sanaa A
authors.initials: SA
authors.lastname: Kenawy
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D018696:Neuroprotective Agents; D009566:Nitrates; D009573:Nitrites; D011720:Pyrazoles; D013449:Sulfonamides; D019001:Nitric Oxide Synthase; D053148:Caspase 3; D000068579:Celecoxib; D019331:NG-Nitroarginine Methyl Ester