Oxidative Stress and Erythrocyte Membrane Alterations in Children with Autism: Correlation with Clinical Features

Abstract

It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na(+)/K(+)-ATPase activity (-66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-ω3 with a consequent increase in ω6/ω3 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD.

Figure 1. Scatter plot showing oxidative stress markers in urine and plasma and antioxidant enzymes activities in erythrocytes.

Au = Autistic children; TD = typically developing children. Horizontal bars indicate means. Standard deviation values and whether parametric or not parametric statistic tests were applied, are reported in Tab. 2. p<0.01 highly significant; p<0.05 significant; ns, not significant.

Figure 2. Scatter plot showing erythrocyte membrane features and molecules.

Au = Autistic children; TD = typically developing children. TMA-DPH and DPH values are inversely correlated with the outer and the inner membrane fluidity, respectively. TBARS = Thiobarbituric Acid Reactive Substances. Horizontal bars indicate means. Standard deviation values and whether parametric or not parametric statistic tests were applied, are reported in Tab. 2. p<0.01 highly significant; p<0.05 significant ns, not significant.

Figure 3. Relevant correlations between Au clinical features and biochemical data.

Au patients were divided into three levels of cognitive/developmental impairment as follows: 1: mild, 2: moderate, 3: severe. TMA-DPH values are inversely correlated with the outer membrane fluidity. SFA = Saturated Fatty Acids. CARS activity level item score denotes hyperactivity. p<0.01 highly significant; p<0.05 significant. More details are reported in Tab.4.