Cyclooxygenase-2 inhibitors differentially attenuate pentylenetetrazolinduced seizures and increase of pro- and anti-inflammatory cytokine levels in the cerebral cortex and hippocampus of mice

Autor(es)

Temp, Fernanda Rossatto ; Marafiga, Joseane Righes ; Milanesi, Laura Hautrive ; Duarte, Thiago ; Rambo, Leonardo Magno ; Pillat, Micheli Mainardi ; Mello, Carlos Fernando

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 810, p. 15-25, SEP 5 2017.
• Citações Web of Science: 7

Resumo

Seizures increase prostaglandin and cytoldne levels in the brain. However, it remains to be determined whether cyclooxygenase-2 (COX-2) derived metabolites play a role in seizure-induced cytokine increase in the brain and whether anticonvulsant activity is shared by all COX-2 inhibitors. In this study we investigated whether three different COX-2 inhibitors alter pentylenetetrazol (PTZ)-induced seizures and increase of interleuldn-1 beta (IL-1 beta), interleukin-6 (IL-6), interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) levels in the hippocampus and cerebral cortex of mice. Adult male albino Swiss mice received nimesulide, celecoxib or etoricoxib (0.2, 2 or 20 mg/kg in 0.1% carboxymethylcellulose (CMC) in 5% Tween 80, p.o.). Sixty minutes thereafter the animals were injected with PTZ (50 mg/kg, i.p.) and the latency to myoclonic jerks and to generalized tonic-clonic seizures were recorded. Twenty minutes after PTZ injection animals were killed and cytokine levels were measured. PTZ increased cytokine levels in the cerebral cortex and hippocampus. While celecoxib and nimesulide attenuated PTZ-induced increase of proinflammatory cytokines in the cerebral cortex, etoricoxib did not. Nimesulide was the only COX-2 inhibitors that attenuated PTZ-induced seizures. This effect coincided with an increase of IL-10 levels in the cerebral cortex and hippocampus, constituting circumstantial evidence that IL-10 increase may be involved in the anticonvulsant effect of nimesulide. (AU)

• Processo FAPESP: 15/19478-3 - Papel do receptor B2 de cininas na patogênese e progressão da doença de Alzheimer família experimental: da neurogênese e resposta imune à cognição
• Beneficiário: Micheli Mainardi Pillat
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado