The influence of anticonvulsant and antioxidant drugs on nitric oxide level and lipid peroxidation in the rat brain during penthylenetetrazole-induced epileptiform model seizures

Nitric oxide (NO) generation in the brain cortex of Wistar rats was measured by direct method of electron paramagnetic resonance (EPR) spectroscopy. Dramatic (fivefold) elevation of NO production was found during penthylenetetrazole (PTZ)-induced epileptiform seizures. The level of secondary products of lipid peroxidation (LPO; thiobarbituric acid reactive substances, TBARS) was also significantly increased in the cerebral cortex of rats with PTZ-evoked seizures. The effects of anticonvulsant drugs phenobarbital, lamotrigine, phenazepam, as well as antioxidant substances alpha-tocopherol and novel original Russian synthetic drug mexidol (2-ethyl-6-methyl-3-oxypiridine succinate), were investigated. All the substances studied significantly decreased seizure manifestations and partially prevented both enhancement of NO generation and increase in TBARS formation. Mexidol and phenobarbital were found to be the most effective in the preventing of PTZ-induced seizures among all the substances studied. The data obtained support our speculation that neuroprotective action of mexidol may correlate with its ability to inhibit not only excessive reactive oxygen species (ROS) formation but also NO generation. While the molecular mechanism underlying action of mexidol and phenobarbital still remains unclear, it is likely that the effect of these drugs on NO production is contributing to their neuroprotective action. It might be concluded that both the suppression of seizure-induced NO generation and LPO enhancement may be involved in the mechanism of action of antiepileptic drugs. (C) 2003 Elsevier Science Inc. All rights reserved.