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

Epilepsy Res. 2010 Sep;91(1):49-56. doi: 10.1016/j.eplepsyres.2010.06.011.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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


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