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Neurotoxic effects of valproic acid in Wistar rats: transgenerational alterations after exposure of the first generation
1  Faculty of Health Sciences, Marien Ngouabi University, Brazzaville, Congo
Academic Editor: Carla Masala

Abstract:

Introduction: Valproic acid (VPA) is a broad-spectrum anticonvulsant that is particularly effective against epilepsy, acting by increasing GABA (cerebral inhibitor) activity and blocking sodium channels. Despite its therapeutic benefits, VPA presents significant risks. Objective: This study aimed to evaluate the neurotoxic effects of VPA in Wistar rats. Methods: Forty-eight male and female Wistar rats were divided into six groups: (1 and 4) a control group, (2 and 5) a VPA 200 mg/kg group, and (3 and 6) a VPA 400 mg/kg group. The products were administered daily by gavage for 60 days. Wistar rats weighing between 100 and 300 g exposed to VPA and their offspring constituted our study population. Daily observations were made for three generations of Wistar rats. Behavioral, biochemical, cerebral histological, and reproductive parameters were evaluated, as well as 8-OH-dG dosage by PCR on one genetic region. Results: Observations revealed significant alterations across three generations. Wistar rats exposed to VPA exhibited brain alterations, reproductive dysfunction, and alopecia. In the second and third generations, our results showed brain atrophy, limb abnormalities, tumors, spina bifida, and histological alterations. Our results highlighted a significant decrease in biochemical parameters, stress, memory impairment, neurodevelopmental disorders, and reproductive system dysfunction. Conclusion: The abnormalities observed in the three generations of Wistar rats during our study reflect VPA-induced neurotoxicity at the doses studied after the exposure of the first generation. Our future work will consist of consolidating a neurotoxicity model based on APV.

Keywords: valproic acid, neurotoxicity, genealogy, neurodevelopmental and morphological disorders, rats
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