Aims: The aim of the present study was to investigate the role of zinc (Zn) in pilocarpine-induced seizures and its interrelation with an antiepileptic drug, namely, valproic acid.

Methodology: The study was carried out on 110 male Wistar albino rats that were divided into the following groups: Group I, control rats that received intraperitoneal (i.p.) saline vehicle; Groups II-V received Zn in a medium dose, Zn in a high dose, valproic acid in a therapeutic dose, as well as a combination of valproic acid with medium dose Zn, respectively, for 3 weeks before saline injection, Group VI received i.p. pilocarpine to induce seizures; Groups VII-XI received Zn in a medium dose, Zn in a high dose, valproic acid in a therapeutic dose, a combination of therapeutic dose of valproic acid with medium dose Zn, as well as a combination of subeffective dose of valproic acid with medium dose of Zn, respectively, for 3 weeks before pilocarpine injection. The seizure's latency and severity for each rat was recorded. Blood and brain hippocampal samples were collected for determination of serum neuron specific enolase (NSE), hippocampal Zn, interleukin-1 beta concentrations as well as hippocampal superoxide dismutase and caspase-3 activities.

Results: The results of the current study demonstrated that pretreatment with high dose of Zn exacerbated pilocarpine-induced seizures. Whereas, a medium dose of Zn and valproic acid either alone or in combination reduced the severity of pilocarpine-induced limbic seizures and increased the latency to attain the forelimb clonus. Also both drugs, either alone or in combination, ameliorated all studied biochemical parameters with the exception of hippocampal Zn concentration, which was only significantly increased by pretreatment with Zn, either alone or in combination with valproic acid.

Conclusions: The present study highlights the antiepileptic role that could be played by Zn, when given in appropriate doses.