Abstract
Background and aims:Autism spectrum disorder (ASD) is a growing prevalence disorder. Oxidative stress is involved in the pathophysiology of ASD. Considering the antioxidant and neuroprotective capacity of trigonelline (TRI), the current study was designed to evaluate the effect of TRI on valproic acid (VPA)-induced ASD in rats, considering its possible antioxidant properties. Methods: To induce ASD, pregnant Wistar rats received a single subcutaneous injection of VPA (600 mg/kg) on gestational day 12. Animals were treated with normal saline (10 ml/kg), TRI (10, 50, and 100 mg/kg), intraperitoneally for one week starting postnatal day 40. Behavioral tests were conducted to assess repetitive behaviors (marble burying test (MBT)), anxiety-like behaviors (elevated plus maze (EPM), memory function (shuttle box test), and social interactions (three chamber test). Blood samples were collected from the heart to evaluate malondialdehyde (MDA) levels and total antioxidant capacity (TAC) in serum. The hippocampus was dissected out to assess MDA and TAC. Data were analyzed using Graph Pad Prism 8. Results: VPA led to anxiety-like behaviors in EPM, passive avoidance memory deficits in shuttle box, repetitive behaviors in MBT, and impairment in social interactions impairment in three chamber test. TRI reversed these behavioral alterations. Moreover, TRI increased hippocampal and serum TAC and reduced MDA levels in the hippocampus and serum samples of ASD rats. Conclusion: These findings revealed that TRI alleviated oxidative stress markers in the hippocampus and serum, suggesting its promising role in reducing ASD-related symptoms in rats partially mediated via its antioxidant properties.