Non-Protein-Bound Iron and 4-Hydroxynonenal Protein Adducts in Autistic Spectrum Disorders

Background:  A potential relationship between oxidative stress (OS) and autism spectrum disorders (ASDs) has been repeatedly explored, nevertheless, the OS contribution in the autism pathogenesis is still not fully elucidated

Objectives:  to evaluate the redox status in ASD

Methods: In this study we investigated for the first time the levels of non-protein-bound iron (NPBI), a pro-oxidant factor, and 4-hydroxynonenal protein adducts (4-HNE-PAs), as a marker of lipid peroxidation-induced protein damage, in children with ASD (n=20, mean age 12.0 ± 6.2 years) .

Results:  Intraerythrocyte and plasma NPBI levels measured by HPLC result significantly increased (1.98- and 3.56-folds) in  patients with ASD, as compared to controls (n=18, mean age 11.7 ± 6.5 years) (p=0.0019 and p<0.0001, respectively). Likewise, immunoblotting analysis shows significantly higher levels of 4-HNE PAs in erythrocyte membranes and in plasma (1.58- and 1.6-folds, respectively) from  patients with ASD (p=0.0043  and p=0.0001, respectively). Antioxidant erythrocyte GSH was slightly decreased (-10.34 %)  in patients (p=0.0215).

Conclusions: Our findings indicate an impairment of the redox status in ASD patients, with a pro-oxidant / antioxidant balance shifted toward the pro-oxidant arm. Increased levels of NPBI could contribute to lipid peroxidation and, consequently, to increased plasma and erythrocyte membranes 4-HNE-PAs, thus amplifying the oxidative damage, potentially contributing to the phenotype of AD.