<b>Background and Objective:</b> Epilepsy is one of the normal neurological problems that came about because of strange electrical movements and prompt serious and far-reaching cell misfortune in the mind. This study aimed to investigate if a nano-Chitosan formulation loaded with bovine milk lactoperoxidase (LPO) and lactoferrin (LF) could prevent Lithium Chloride/Pilocarpine-induced epilepsy in rats or not. <b>Materials and Methods:</b> Adult male rats (200-250 g) were partitioned into four groups (8 animals each) as follows: Group (1) Normal rats served as control group and received saline orally, group (2) Normal rats ingested with a daily oral dose of LPO and LF-NPS formulation at 50 mg kg<sup></sup><sup>1</sup>, group (3) Pilocarpine-induced epileptic rats and group (4) Epilepsy-modeled rats were treated with LPO+LF NPs (50 mg/kg/day, orally) for 6 weeks. <b>Results:</b> The results revealed that the administration of LPO+LF-NPs markedly improved the induced-epilepsy disorders, this was monitored from the significant reduction in the values of caspase-3, TNF-α, IL-1β, CD4<sup>+</sup>, MDA and NO coupled with remarkable raise in AchE-ase, dopamine, serotonin, SOD and GPx, CAT and GSH values in both brain regions. <b>Conclusion:</b> This study supported the anti-epilepsy features of LPO+LF-NPS against Lithium Chloride/Pilocarpine-induced epilepsy in rats through the improvement of the immune response, reduction of inflammation and restoration of the impaired oxidative stress status.
Keywords: Epilepsy; LPO and LF; biogenic amines; lithium chloride/pilocarpine; nano-formulation; oxidative stress markers.