Effects of Valproate and Deferoxamine on Epileptiform Activity, Oxidative Stress, and Nitric Oxide in a...

Oxidative and nitrosative stress contribute to epileptogenesis and seizure-related neuronal injury through iron-mediated reactive oxygen species generation and excessive nitric oxide production. This study examined whether combining valproate (VALP) with the iron chelator deferoxamine (DFO) produces additional electrophysiological or biochemical effects in a penicillin-induced model of epileptiform activity. Male Wistar rats were assigned to four groups (n = 7/group): penicillin control, VALP (500 mg/kg), DFO (100 mg/kg), and VALP + DFO. Epileptiform activity was induced by intracortical penicillin and monitored by electrocorticography for 180 min, and spike frequency, spike amplitude, serum and hippocampal total antioxidant status, total oxidant status, oxidative stress index, and nitric oxide levels were measured. VALP, DFO, and their combination significantly reduced spike frequency and amplitude versus penicillin. Although VALP + DFO did not further suppress spike frequency or spike amplitude compared with VALP alone, the combination was associated with selected biochemical differences, including lower serum and hippocampal nitrite/nitrate surrogate levels and higher hippocampal total antioxidant status. These findings suggest that VALP + DFO produces selected, marker-specific biochemical changes beyond VALP monotherapy, without providing additional anticonvulsant efficacy in this acute model. The functional significance of these biochemical changes remains to be established.