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: Sarah A Abd El-Aal, Maha M El-Sawalhi, Mona Seif-El-Nasr, Sanaa A Kenawy
• Journal: Drug and chemical toxicology (Drug Chem Toxicol) Vol. 36 Issue 4 Pg. 385-95 (Oct 2013) ISSN: 1525-6014 [Electronic] United States
• PMID: 23298270 (Publication Type: Journal Article)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Neuroprotective Agents
• Nitrates
• Nitrites
• Pyrazoles
• Sulfonamides
• Nitric Oxide Synthase
• Caspase 3
• Celecoxib
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Caspase 3 (metabolism)
• Celecoxib
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Hippocampus (drug effects, enzymology, pathology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Neuroprotective Agents (pharmacology)
• Nitrates (metabolism)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitrites (metabolism)
• Pyrazoles (pharmacology)
• Rats
• Reperfusion Injury (drug therapy, pathology)
• Sulfonamides (pharmacology)
• Time Factors