Cox-2 inhibition can lead to adverse effects in a rat model for temporal lobe epilepsy.

Abstract

PURPOSE:

Status epilepticus (SE) leads to upregulation of pro-inflammatory proteins including cyclooxygenase-2 (cox-2) which could be implicated in the epileptogenic process and epileptic seizures. Recent studies show that cox-2 can regulate expression of P-glycoprotein (P-gp) during epileptogenesis and epilepsy. P-gp could cause pharmacoresistance by reducing brain entry of anti-epileptic drugs such as phenytoin (PHT). Here we have investigated the effects of cox-2 inhibition on epileptogenesis, spontaneous seizures and PHT treatment in a rat model for temporal lobe epilepsy (TLE).

METHODS:

A 3-day treatment with the cox-2 inhibitor SC-58236 (SC) was started 1 day before electrically induced SE. Chronic epileptic rats were treated with SC for 14 days, which was followed by a 7-day period of SC/PHT combination treatment. Seizure activity was monitored continuously using electroencephalography.

RESULTS:

SC treatment did not affect SE duration, but led to an increased number of rats that died during the first 2 weeks after SE. Cox-2 inhibition during the chronic period led to an increased number of seizures in the 2nd week of treatment in 50% of the rats. SC/PHT treatment reduced seizures significantly for only 2 days.

CONCLUSIONS:

Both SC treatment that started before SE and the 14-day treatment in chronic epileptic rats led to adverse effects in the TLE rat model. Despite a temporal reduction in seizure frequency with SC/PHT treatment, SC does not seem to be a suitable approach for anti-epileptogenic or anti-epileptic therapy.

• Authors: Linda Holtman, Erwin A van Vliet, Peter M Edelbroek, Eleonora Aronica, Jan A Gorter
• Journal: Epilepsy research (Epilepsy Res) Vol. 91 Issue 1 Pg. 49-56 (Sep 2010) ISSN: 1872-6844 [Electronic] Netherlands
• PMID: 20643531 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

• 4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
• Cyclooxygenase 2 Inhibitors
• Pyrazoles
• Sulfonamides
• Cyclooxygenase 2

Topics

• Animals
• Chronic Disease
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase 2 Inhibitors (adverse effects)
• Disease Models, Animal
• Electroencephalography (drug effects)
• Epilepsy, Temporal Lobe (enzymology, mortality, physiopathology)
• Male
• Pyrazoles (adverse effects)
• Rats
• Rats, Sprague-Dawley
• Sulfonamides (adverse effects)