Selenium deficiency and altered Cu/Se, Zn/Se and Cu/Zn ratios associated with GPx1 activity: non-invasive biomarkers of oxidative stress in autism spectrum disorders

Free Radic Biol Med. 2025 Dec 1:240:685-692. doi: 10.1016/j.freeradbiomed.2025.09.005. Epub 2025 Sep 3.

Abstract

Metal micronutrient dyshomeostasis appears to be involved in the risk of autism spectrum disorders (ASD). Selenium (Se), copper (Cu) and zinc (Zn) are essential for the defence against oxidative stress (OS), a key factor in the maintenance of synaptogenesis and neurogenesis. This study assessed plasma concentrations of Se, Cu, and Zn, along with their ratios, malondialdehyde (MDA) levels, and erythrocyte glutathione peroxidase (GPx1) activity in Algerian children with ASD. A total of 30 subjects diagnosed with ASD and 32 neurotypically developing (ND) children participated in this study. Trace element levels were measured using a polarographic analyzer. Plasma MDA was determined by UV spectrophotometry and erythrocyte GPx1 activity using a SPECORD® 210 plus dual beam spectrophotometer (Analytik Jena German). The Cu/Zn ratio was significantly lower in children with ASD (p < 0.001), while no significant difference was found for MDA between the two study groups. However, in children with ASD, a positive correlation was found between MDA and the plasma Cu/Zn ratio (r = 0.6874, p = 0.005). Se levels and GPx1 erythrocyte activity were significantly lower in children with ASD compared with the ND children (p < 0.001; p < 0.05). Cu/Se and Zn/Se ratios were significantly higher in children with ASD (p < 0.001). Sex-stratified analysis indicated a specific vulnerability to OS among boys with ASD, while no significant age-related differences were observed in children with ASD. These findings suggest that imbalances in micronutrient ratios and a decrease in GPx1 activity favor OS, potentially contributing to ASD pathogenesis in extreme western Algeria.

Keywords: Autism spectrum disorders; Cu; Glutathione peroxidase 1; MDA; Plasma markers (Se; Polarography; Zn).

MeSH terms

  • Autism Spectrum Disorder* / blood
  • Autism Spectrum Disorder* / metabolism
  • Autism Spectrum Disorder* / pathology
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Copper* / blood
  • Erythrocytes / metabolism
  • Female
  • Glutathione Peroxidase GPX1
  • Glutathione Peroxidase* / blood
  • Glutathione Peroxidase* / metabolism
  • Humans
  • Male
  • Malondialdehyde / blood
  • Oxidative Stress
  • Selenium* / blood
  • Selenium* / deficiency
  • Zinc* / blood

Substances

  • Selenium
  • Copper
  • Glutathione Peroxidase
  • Zinc
  • Glutathione Peroxidase GPX1
  • Biomarkers
  • GPX1 protein, human
  • Malondialdehyde