Figure 4

Proposed shifts in oxidative-antioxidative balances in children with autism spectrum disorder. The numbers indicated in the figure correspond to the following steps: (1) the primary pathogenesis is an attenuation of the reduced glutathione (GSH) system in the central nervous system²⁵. (2) This increases the hydroxyl radical formation, leading to elevations in 8-hydroxy-2′-deoxyguanosine (8-OHdG) and coenzyme Q10 (CoQ10) oxidation rate⁴⁷. (3) Step 2 may result in increased levels of lipid alkoxyl and alkylperoxyl radicals; however, the antioxidative activities against these radicals are enhanced by elevated α-tocopherol levels and unknown feedback system(s). (4) The superoxide scavenging activity is also increased via an unknown feedback system involving superoxide dismutase. (5) Despite the increase in superoxide dismutase activity, the cytoplasmic glutathione peroxidase (GPx) activity is reduced, so hydrogen peroxide (H₂O₂) may be present in relative excess. (6) This increase in hydrogen peroxide further enhances the production of hydroxyl radicals, and finally, this reactive oxygen species chain reaction expands. Molecules in squares indicate those evaluated in the present study. Asterisks indicate results reported in previous studies. Red letters and lines indicate prooxidative pathways, blue letters and lines indicate antioxidative pathways, and black letters and lines indicate unaffected or neutral pathways.