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.