Omega 3 polyunsaturated fatty acids enhance the protective effect of levetiracetam against seizures, cognitive impairment and hippocampal oxidative DNA damage in young kindled rats

Pharmacol Biochem Behav. 2015 Aug;135:105-13. doi: 10.1016/j.pbb.2015.05.020. Epub 2015 Jun 1.


Levetiracetam (LEV) is a unique, effective, relatively safe antiepileptic drug that preferentially interacts with synaptic vesicle protein 2A (SV2A). This study aimed to explore the effect of combined treatment of LEV with omega 3 (OM3) on cognitive impairment and hippocampal oxidative stress and DNA damage induced by seizures in the PTZ-kindled young rat model. Cognitive functions, biomarkers of oxidative stress, and DNA damage were assessed in PTZ-kindled young rats pretreated with single and combined treatment of LEV (30mg/kg, i.p.) and OM3 (200mg/kg, p.o.). Pretreatment with LEV and OM3 at the tested doses significantly attenuated PTZ-induced seizures and decreased cognitive impairment in both passive avoidance and elevated plus maze tests in the PTZ-kindled rats. Moreover, the increase in hippocampal glutamate, malondialdehyde and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, as well as the decrease in reduced glutathione (GSH) levels and GSH-peroxidase and superoxide dismutase activities induced by PTZ kindling, significantly decreased. These effects were higher with combined treatment of LEV with OM3 and significantly more than the observed effects of single LEV or OM3. In conclusion, the combined treatment of LEV with OM3 is more effective in seizure control and alleviating the cognitive impairment induced by PTZ kindling in the young rat model, the effects that result from the decrease in hippocampal oxidative stress and DNA damage which can be attributed to the antioxidant properties of both LEV and OM3. These results may be promising for the use of LEV and OM3 combination in the treatment of epileptic children.

Keywords: Cognition; DNA damage; Levetiracetam; Omega 3; Oxidative stress; PTZ kindling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Anxiety / psychology
  • Avoidance Learning / drug effects
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / psychology*
  • Convulsants / pharmacology
  • DNA Damage*
  • Drug Synergism
  • Fatty Acids, Omega-3 / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Kindling, Neurologic / drug effects*
  • Levetiracetam
  • Male
  • Oxidative Stress / drug effects
  • Pentylenetetrazole / pharmacology
  • Piracetam / analogs & derivatives*
  • Piracetam / pharmacology
  • Rats
  • Rats, Wistar
  • Seizures / drug therapy*


  • Anticonvulsants
  • Convulsants
  • Fatty Acids, Omega-3
  • Levetiracetam
  • Pentylenetetrazole
  • Piracetam