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Title: Cyclooxygenase-2/PGE(2) pathway facilitates pentylenetetrazol-induced seizures
Authors: Oliveira, Mauro Schneider
Furian, Ana Flavia
Freire Royes, Luiz Fernando
Fighera, Michele Rechia
Fiorenza, Natalia Gindri
Castelli, Marcelo
Machado, Pablo
Bohrer, Denise
Veiga, Marlei
Ferreira, Juliano
Cavalheiro, Esper Abraao [UNIFESP]
Mello, Carlos Fernando
Universidade Federal de Sergipe (UFS)
Univ Fed Rio Grande do Sul
Universidade Federal de São Paulo (UNIFESP)
Keywords: COX-2
Issue Date: 1-Mar-2008
Publisher: Elsevier B.V.
Citation: Epilepsy Research. Amsterdam: Elsevier B.V., v. 79, n. 1, p. 14-21, 2008.
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.
ISSN: 0920-1211
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