Vitamin E-Valproate Co-Therapy Attenuated oxidative stress, neuroinflammation, related cognitive deficits and neuronal damage in Cypermethrin exacerbated seizure

Background: Epilepsy, characterized by recurrent seizures and associated cognitive impairments, is often exacerbated by environmental neurotoxins such as Cypermethrin. This study investigates the effects of Cypermethrin (CPM) on Pentylenetetrazole (PTZ)-induced seizures and the potential neuroprotective properties of Vitamin E (VIT E) and valproate (VAP), both alone and in combination. Methods: Behavioral tests, biochemical assays, and immunohistochemical analyses were conducted to assess seizure severity, cognitive performance, neuronal integrity, and markers of neuroinflammation and oxidative stress. Results: PTZ-induced seizures significantly increased seizure severity and impaired cognitive performance in the T-maze, Y-maze, and Morris’ water maze tests, with these deficits being exacerbated by CPM. Immunohistochemical staining revealed substantial neuronal and interneuron loss in the hippocampus, accompanied by heightened microglial activation. Biochemical analyses showed elevated levels of pro-inflammatory cytokines (TNF-α) and oxidative stress markers (MDA), alongside reduced antioxidant enzyme activity (SOD). Therapeutic intervention with VAP or VIT E mitigated these effects to varying degrees. Combination therapy was particularly effective, demonstrating significant improvements in seizure scores, cognitive performance, neuronal integrity, and reductions in neuroinflammation and oxidative stress markers. These findings underscore the potential synergistic benefits of combining VAP and VIT E in managing seizures and associated neuropathologies. Conclusion: This study highlights the exacerbating effects of environmental toxins on seizure-related cognitive and neuronal impairments while providing evidence for antioxidant-based combination therapies as a promising approach to mitigate these effects.