Abstract
This pilot study investigated the relationship between nuclear transcription factor Nrf2 and glutathione homeostasis in children with autism spectrum disorder (ASD), addressing the role of oxidative stress in ASD pathophysiology. Oxidative stress, characterized by an imbalance between reactive oxygen species and antioxidant defenses, has been implicated in ASD and may contribute to neuroinflammation and mitochondrial dysfunction. Nrf2, a key regulator of the antioxidant response, influences glutathione synthesis and recycling, making it critical for cellular redox balance. This study included 23 children with ASD and 21 neurotypical healthy controls, and measured levels of Nrf2, Keap1 (Kelch-like ECH-associated protein 1), reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), and peroxidase (GPx3) in blood samples. Our study reveals altered antioxidant defense in children with autism spectrum disorder, as evidenced by reduced levels of Nrf2, Keap1, GSH, and GR, along with elevated GSSG and a lower GSH/GSSG ratio. These findings indicate an increased oxidative stress burden in this population. Additionally, the observed positive correlation between Nrf2, GSH, and GR levels suggests an important role for Nrf2 in maintaining glutathione homeostasis. Our results underscore the potential involvement of oxidative stress in ASD and emphasize the need for further research into targeted therapeutic approaches to address this imbalance.