Cyclooxygenase-2/PGE(2) pathway facilitates pentylenetetrazol-induced seizures

Cyclooxygenase-2/PGE(2) pathway facilitates pentylenetetrazol-induced seizures

Author Oliveira, Mauro Schneider Google Scholar
Furian, Ana Flavia Google Scholar
Freire Royes, Luiz Fernando Google Scholar
Fighera, Michele Rechia Google Scholar
Fiorenza, Natalia Gindri Google Scholar
Castelli, Marcelo Google Scholar
Machado, Pablo Google Scholar
Bohrer, Denise Google Scholar
Veiga, Marlei Google Scholar
Ferreira, Juliano Google Scholar
Cavalheiro, Esper Abraao Autor UNIFESP Google Scholar
Mello, Carlos Fernando Google Scholar
Institution Universidade Federal de Sergipe (UFS)
Univ Fed Rio Grande do Sul
Universidade Federal de São Paulo (UNIFESP)
Abstract Cyclooxygenases (CCXs) are rate-limiting enzymes in the metabolic pathways in which arachidonic acid is converted to prostaglandins. COX-2 is the isoform induced at injury/inflammation sites and expressed constitutively in a few tissues, such as the central nervous system, and plays a rote in neurodegenerative diseases associated with increased excitatory activity. However, the role of COX-2 and its main product, prostaglandin E-2 (PGE(2)), in the convulsive states is not fully established. in this study we showed that the selective COX-2 inhibitor, celecoxib (at the dose of 2mg/kg, but not at the doses of 0.2 or 20mg/kg, p.o.), protects against the seizures induced by pentylenetetrazol (PTZ, 60 mg/kg, i.p.). the role of PGE2 in the convulsions induced by PTZ was further investigated by administering anti-PGE(2) antibodies (4 mu g/2 mu l, i.c.v.), and assessing electroencephatographic changes induced by PTZ (PTZ, 60 mg/kg, i.p.). Anti-PGE(2) antibodies attenuated PTZ-induced seizures in rats. in addition, combining PGE(2) (100 ng/2 mu l, i.c.v.) with a subconvulsant dose of PTZ (20 mg/kg, i.p.) caused seizures, further supporting a role for this prostaglandin in the convulsions induced by PTZ. Finally, we showed that the anticonvulsant action of celecoxib (2 mg/kg, p.o.) was reversed by the intracerebroventricular administration of PGE(2) (10 ng/2 mu l, i.c.v.). These data constitute strong converging pharmacological evidence supporting a facilitatory role for the COX-2/PGE2 pathway in the seizures induced by PTZ. However, whether selective COX-2 inhibitors are safer anti-inflammatory drugs for epileptic patients than nonspecific inhibitors remains to be determined. (c) 2008 Elsevier B.V. All rights reserved.
Keywords COX-2
celecoxib
epilepsy
PGE(2)
EEG
PTZ
Language English
Date 2008-03-01
Published in Epilepsy Research. Amsterdam: Elsevier B.V., v. 79, n. 1, p. 14-21, 2008.
ISSN 0920-1211 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 14-21
Origin http://dx.doi.org/10.1016/j.eplepsyres.2007.12.008
Access rights Closed access
Type Article
Web of Science ID WOS:000255453900003
URI http://repositorio.unifesp.br/handle/11600/30501

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