Experimental Brain Research

, Volume 174, Issue 1, pp 109–113 | Cite as

The effects of vitamin E on penicillin-induced epileptiform activity in rats

  • Mustafa Ayyıldız
  • Mehmet Yıldırım
  • Erdal AgarEmail author
Research Article


Epilepsy is a disorder characterized by recurrent seizures, which can increase the content of reactive oxygen in the brain. Active oxygen free radical scavengers such as ascorbic acid or α-tocopherol (vitamin E) might prevent epilepsy. A variety of animal seizure models exist which help to document the effects of vitamin E and specify its action. In this study, we have evaluated dose-dependent effect of α-tocopherol on penicillin-induced epileptiform activity, analyzed by electrocorticogram (ECoG). The epileptiform activity was induced by microinjection of penicillin into the left sensorimotor cortex. Thirty minutes after penicillin injection, 100, 300, or 500 mg/kg of α-tocopherol was administrated intramuscularly (i.m.). α-Tocopherol (100, 300, or 500 mg/kg) alone did not significantly change the spike amplitudes in non-penicillin pretreated control animals. α-Tocopherol of 300, or 500 mg/kg significantly decreased the frequency of epileptiform activity in the penicillin-pretreated animals. The low dose of α-tocopherol (100 mg/kg) did not significantly change either amplitude or frequency of epileptiform activity. α-Tocopherol of 500 mg/kg i.m. was the most effective dose in changing of frequency on penicillin-induced epileptiform activity. The anti-convulsant effects of α-tocopherol appeared 80, 60, 30 min after α-tocopherol injection in 300, 500, and 3 day vitamin E supplemented groups. These data indicate that α-tocopherol decreases the frequency of penicillin-induced epileptic activity.


α-Tocopherol Vitamin E Penicillin Epileptiform activity ECoG 


  1. Avanzini G, Franceschetti S (2003) Cellular biology of epileptogenesis. Lancet 2:33–42CrossRefGoogle Scholar
  2. Ayyildiz M, Yildirim M, Agar E, Baltaci AK (2006) The effect of leptin on penicillin-induced epileptiform activity in rats. Brain Res Bull 68:374–378CrossRefPubMedGoogle Scholar
  3. Drevon CA (1991) Absorption, transport and metabolism of vitamin E. Free Radic Res Commun 14:229–246PubMedCrossRefGoogle Scholar
  4. Frantseva MV, Velazquez JLP, Tsoraklidis G, Mendonca AJ, Adamchik Y, Mills LR, Carlen PL, Burnham MW (2000) Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy. Neuroscience 97:431–435CrossRefPubMedGoogle Scholar
  5. Godlevskii LS, Stepanenko KI, Lobasyuk BA, Sarakhan EV, Bobkova LM (2004) The effects of electrical stimulation of the paleocerebellar cortex on penicillin-induced convulsive activity in rats. Neurosci Behav Physiol 34:797–802CrossRefPubMedGoogle Scholar
  6. Halliwell B, Gutteridge JMC (1990) The antioxidants of human extracellular fluids. Arch Biochem Biophys 280:1–8CrossRefPubMedGoogle Scholar
  7. Horwitt MK (1979) The vitamins: vitamin E. In: Goodhart RS, Shils ME (eds) Modern nutrition in health and disease. Lea and Febirger, PhiladelphiaGoogle Scholar
  8. Jerrett SA, Jefferson D, Mengel CE (1973) Seizure H2O2 and lipid peroxidase in brain during exposure to oxygen under high pressure. Aeroesp Med 44:40–44Google Scholar
  9. Kabuto H, Yokoi I, Ogawa N (1998) Melatonin inhibits iron-induced epileptic discharges in rats by suppressing peroxidation. Epilepsia 30:237–243CrossRefGoogle Scholar
  10. Kovacs R, Schucmann S, Gabriel S, Kann O, Kardos J, Heinemnn U (2002) Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures. J Neurophysiol 88:2909–2918PubMedCrossRefGoogle Scholar
  11. Koteghawa M, Sugiyama M, Shoji T, Haramaki N, Ogura R (1993) Effect of α-tocopherol on high energy phosphate metabolite levels in rat heart by P-NMR using a Langendoff perfusion technique. J Mol Cell Cardiol 25:1067–1074CrossRefPubMedGoogle Scholar
  12. Kryzhanovskii GN, Nikushkin EV, Braslavskii VE, Glebov RN (1980) Lipoperoxidation in the hyperactive focus of rat cerebral cortex. Biull Eksp Biol Med 89:14–16PubMedGoogle Scholar
  13. Levy Sl, Burnham WM, Bishai A, Hwang PA (1990) An evaluation of the anticonvulsant effects of vitamin E. Epilepsy Res 6:12–17CrossRefPubMedGoogle Scholar
  14. Levy Sl, Burnham WM, Bishai A, Hwang PA (1992) The anticonvulsant effects of vitamin E: a further evaluation. Can J Neurol Sci 19:201–203PubMedGoogle Scholar
  15. Marangoz C, Ayyildiz M, Agar E (1994) Evidence that sodium nitroprusside possesses anticonvulsant effects mediated through nitric oxide. Neuroreport 5:2454–2456PubMedCrossRefGoogle Scholar
  16. Ogunmekan AO (1985) Plasma vitamin E levels in apparently normal children with and without anticonvulsant drug therapy. Trop Geogr Med 37:175–1777PubMedGoogle Scholar
  17. Ogunmekan AO, Hwang PA (1989) A randomized, double-blind, placebo-controlled, clinical trial of D α-tocopheryl acetate (vitamin E), as add-on therapy, for epilepsy in children. Epilepsia 30:84–89PubMedCrossRefGoogle Scholar
  18. Oliver CN, Starke-Reed PE, Stadtman ER, Lin GJ, Correy JM, Floyd RA (1990) Oxidative damage to brain proteins, loss of glutamine synthetase activity and production of free radicals during ischemia/reperfusion induced injury to gerbil brain. Proc Natl Acad Sci USA 87:5144–5147PubMedCrossRefGoogle Scholar
  19. Rauca C, Wiswedel I, Zerbe R, Keilhoff G, Krug M (2004) The role of superoxide dismutase and α-tocopherol in the development of seizures and kindling induced by pentylenetetrazol-influence of the radical scavenger α-phenyl-N-tert-buthyl nitrone. Brain Res 109:203–212CrossRefGoogle Scholar
  20. Ribeiro MCP, Avila DS de, Schneider CYM, Hermes FS, Furian AF, Oliveira MS, Rubin MA, Lehmann M, Kreiglstein J, Mello CF (2005) Α-Tocopherol protects against pentylenetetrazol-and methylmalonate-induced convulsions. Epilepsy Res 66:185–194CrossRefPubMedGoogle Scholar
  21. Sridharan R (2002) Epidemiology of epilepsy. Curr Sci 82:664–670Google Scholar
  22. Steffens M, Huppertz HJ, Zentner J, Chauzit E, Feuerstein TJ (2005) Unchanged glutamine synthetase activity and increased NMDA receptor density in epileptic human neocortex: implications for the pathophysiology of epilepsy. Neurochem Int 47:379–384CrossRefPubMedGoogle Scholar
  23. Sudha K, Ashalatha VR, Rao A (2001) Oxidative stress and antioxidants in epilepsy. Clin Chimica Acta 303:19–24CrossRefGoogle Scholar
  24. Tucker JM, Townsend DM (2005) Alpha-tocopherol:roles in prevention and therapy of human disease. Biomed Pharmacother 59:380–387CrossRefPubMedGoogle Scholar
  25. Vatassery GT, Adityanjee, Quach HT, Smith WE, Kuskowski MA, Melnyk D (2004) Alpha and gamma tocopherols in cerebrospinal fluid and serum from older male, human subjects. J Am Coll Nutr 23(3):233–238PubMedGoogle Scholar
  26. Willmore LJ, Rubin JJ (1981) Antioxidant pretreatment and iron-induced epileptiform discharges in the rat: EEG and histopathologic studies. Neurology 31:63–69PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Mustafa Ayyıldız
    • 1
  • Mehmet Yıldırım
    • 1
  • Erdal Agar
    • 1
    Email author
  1. 1.Department of Physiology, Faculty of MedicineUniversity of Ondokuz MayisSamsunTurkey

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