Vitamin E-valproate co-therapy attenuated oxidative stress, neuroinflammation, related cognitive deficits and neuronal damage in Cypermethrin exacerbated seizure

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. Behavioral tests, biochemical assays, and immunohistochemical analyses were conducted to assess seizure severity, cognitive performance, neuronal integrity, and markers of neuroinflammation and oxidative stress. 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, demonstrating 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. 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. The following are the highlights from the study: Co-administration of cypermethrin exacerbates ptz-induced seizures and impairs cognitive performance in rats across seizure scoring, T-maze, Y-maze, and Morris’ water maze tests. Co-administration of Cypermethrin with PTZ Exacerbates Neuronal and Interneuron Loss in the Hippocampus, Correlating with Cognitive Deficits. Co-administration of Cypermethrin with PTZ Intensifies Neuroinflammation and Oxidative Stress, Correlating with Increased Microglial Activation and Neuronal Damage. Valproate and Vitamin E Partially Ameliorate PTZ + CPM-Induced Cognitive Deficits Despite Limited Impact on Seizure Severity. Combination Therapy with Valproate and Vitamin E Restores Neuronal and Interneuron Integrity in the Hippocampus Following PTZ + CPM-Induced Damage. Combination Therapy with Valproate and Vitamin E Mitigates Neuroinflammation and Oxidative Stress in PTZ + CPM-Induced Brain Damage.