Effect of valproic acid alone or combined with low dose gamma irradiation in modulating PTZ-induced convulsions in rats involving AKT/m-TOR pathway.

OBJECTIVE

The current study evaluates the anticonvulsant effect of valproic acid (VPA) alone or combined with low dose γ-irradiation (LDR) against pentylenetetrazol-induced convulsions in rats.

METHODS

Five groups of rats were used, group I served as normal control, group II served as PTZ- control and the other three groups were pretreated with single LDR(o.5 Gy), VPA(150 mg/kg i.p.5 days) and VPA with LDR respectively before PTZ injection. Racine score, latency and duration of convulsions were assessed. Evaluation of brain neurotransmitters (glutamate and GABA) as well as AKT/m-TOR pathway (protein kinase B [AKT], mammalian target of rapamycin [m-TOR], protein S6 and caspase 3). Measurement of oxidative stress (Malondialdehyde, glutathione and nitric oxide) was carried out. Histopathological examinations of hippocampi were done.

RESULTS

PTZ resulted in behavioural changes (high Racine score, long seizure duration and short latency).PTZ enhanced oxidative stress state (high MDA and NO, as well as low GSH) compared to normal control. VPA alone or combined with LDR ameliorated, the convulsions and caused significant improvement in behavioural changes and other tested parameters compared to normal control. Histopathological examination of hippocampi was carried out to adjoin the biochemical changes. Certain changes were observed after PTZ injection. However, normal pictures of the other tested groups.

CONCLUSIONS

The previously mentioned findings support that LDR purveyed novel anticonvulsant activity which could offer a possible contributor in the basic treatment of convulsions. This effect might be due to modulation of AkT/m-TOR pathway, reduction of oxidative stress and modulation of neurotransmitters.