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

Alessandro Ghezzo, Paola Visconti, Provvidenza M Abruzzo, Alessandra Bolotta, Carla Ferreri, Giuseppe Gobbi, Gemma Malisardi, Stefano Manfredini, Marina Marini, Laura Nanetti, Emanuela Pipitone, Francesca Raffaelli, Federica Resca, Arianna Vignini, Laura Mazzanti, Alessandro Ghezzo, Paola Visconti, Provvidenza M Abruzzo, Alessandra Bolotta, Carla Ferreri, Giuseppe Gobbi, Gemma Malisardi, Stefano Manfredini, Marina Marini, Laura Nanetti, Emanuela Pipitone, Francesca Raffaelli, Federica Resca, Arianna Vignini, Laura Mazzanti

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Scatter plot showing oxidative stress…
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. pns, not significant.
Figure 2. Scatter plot showing erythrocyte membrane…
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. pns, not significant.
Figure 3. Relevant correlations between Au clinical…
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

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