title: alpha-Tocopheryl-L-ascorbate-2-O-phosphate diester, a hydroxyl radical scavenger, prevents the occurrence of epileptic foci in a rat model of post-traumatic epilepsy.
abstract: Intracortical injection of iron ions has been used to model post-traumatic epilepsy. The results obtained using these models suggest that oxidation of neural membranes by active oxygen free radicals may be involved in the etiology of post-traumatic epilepsy. This is a study of the effects of alpha-tocopheryl-L-ascorbate-2-O-phosphate diester potassium salt (EPC-K1), known as a hydroxyl radical scavenger, on the peroxidation of neural membranes by FeCl(3) in vitro and on the occurrence of epileptic discharges in the FeCl(3) injected post-traumatic epilepsy model rats. EPC-K1 dose-dependently inhibited the production of thiobarbituric acid reactive substances (TBARS) and protein carbonyl (P-Carb), both indices of biogenic macromolecular peroxidation. In vivo studies, sporadic spike discharges and/or epileptiform activities were observed in electrocorticograms (ECoG) of male Sprague-Dawley rat 15-90 min after 500 nmol of FeCl(3) was injected into the motor cortex. On the other hand, when 200 mg/kg of EPC-K1 was injected intraperitoneally 60 min prior to the injection of FeCl(3), the occurrence of epileptic discharges was prevented or delayed. When EPC-K1 (2.5-5 nmol) was injected along with the ferric ions, the occurrence of epileptiform activities was also prevented or delayed. EPC-K1 prevented the induction of early convulsion, the major risk factor of post-traumatic epilepsy. Rats in the Fe+EPC group were injected with 500 nmol of FeCl(3) into the left motor cortex and were given an EPC-K1-diet (CE-2 chow contained 0.2% of EPC-K1, and daily EPC-K1 intake was about 80 mg/kg/day). In the Fe+EPC group rats, the percent induction of epileptic discharges in ECoGs was significantly lower than that in the Fe+CE group rats, which were fed CE-2 after FeCl(3) injection. In the homotropic contra lateral cortex, TBARS and P-Carb content did not show any changes. However, the relative TBARS content in the focal area significantly increased in the Fe+CE and Fe+EPC group rats 3 h after the injection. It became normal 3 days after in the Fe+EPC group. The relative P-Carb content in the focal area significantly increased in the Fe+CE and Fe+EPC group rats 3 h after the injection. However, it became normal after 3 days. In the present study, EPC-K1, which consists of vitamins E and C connected by a phosphate, protected the oxidation of neural membranes and prevented the occurrence of ferric ion-induced epileptic discharges by its radical scavenger activity. These data suggest that EPC-K1 may be clinically useful in not only preventing the focus formation of post-traumatic epilepsy, but also in treating and attenuating the progression of free radical-induced degenerative disorders.
authors.affiliation: Department of Brain Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, 700-8558, Okayama, Japan
authors.forename: Nihei
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kabuto
authors.forename: Sigekiyo
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Norio
authors.initials: N
authors.lastname: Ogawa
authors.forename: Isao
authors.initials: I
authors.lastname: Yokoi