Neurotoxicity, Hepatotoxicity and Behavioral Effects of Valproic Acid in Autism-like Rats

Didou, Latifa; Chakit, Miloud; Kacimi, Fatima-Ezzahra; Ed-Day, Soumia; Boulbaroud, Samira; Azzaoui, Fatima-zahra

doi:10.21608/ejvs.2025.369217.2712

Neurotoxicity, Hepatotoxicity and Behavioral Effects of Valproic Acid in Autism-like Rats

Document Type : Original Article

Authors

¹ Biology and Health Laboratory, Faculty of Sciences, Ibn Tofail University, Kenitra, Morocco.

² Biotechnology and Sustainable Development of Natural Resources Laboratory, Polydisciplinary Faculty, Sultan Moulay Slimane University, Beni Mellal, Morocco

10.21608/ejvs.2025.369217.2712

Abstract

Autism is a neurodevelopmental disorder with serious psychological consequences manifested by social reciprocity and communication disorders. The study explored the influence of valproic acid (VAP) administration on behavioral and histobiochemical markers in autism-like rats. Male Wistar rats were distributed into two groups: The control (T) received saline solution (NaCl 9%), and the treated group (VAP): received valproic acid at 500 mg/kg. Behavioral impairment was measured by different paradigms to evaluate social interaction, memory, and anxiety. Then, the brain and liver were removed for biochemical and histological examinations. Prenatal exposure to VPA at day 12.5 causes long-term effects on behavior in rats, notably a significant reduction of social interactions and memory and an increase in anxiety. The oxidative markers (MDA and CAT) were altered, expressed by an increase of MDA levels in the prefrontal cortex and hippocampus. However, the enzymatic antioxidant activity of CAT in the same areas was depleted. Widespread abnormalities in the brain and liver structure were observed at viable cell levels (pyramidal neurons and Purkinje cells, hepatocytes). In conclusion, in utero VPA exposure causes abnormalities in the brain and liver structures (Purkinje cells and pyramidal neurons) that might be related to oxidative stress. Furthermore, understanding the altered brain architecture involved in neurogenesis and the neurotransmission and its related behavior induced by VPA exposure is needed.

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