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Decreased total antioxidant capacity has a larger effect size than increased oxidant levels in urine in individuals with autism spectrum disorder

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Abstract

Oxidant/antioxidant imbalance may contribute to the pathophysiology of autism spectrum disorder (ASD). We assayed urinary levels of oxidative stress related biomarkers, hexanoyl-lysine (HEL), total antioxidant capacity (TAOC), the DNA methylation biomarker 8-hydroxy-2′-deoxyguanosine (8-OHdG), and plasma levels of superoxide dismutase (SOD), which is major antioxidant enzyme. We examined the relationship between these four biomarkers and social responsiveness in 20 individuals with ASD and in 11 healthy controls. The sex (ASD group, 7/13 vs. control group, 4/7) and age distributions (ASD group, 10.7 ± 5.0 years vs. control group, 14.7 ± 6.3 years) were not significantly different between the groups. Social responsiveness was assessed using the social responsiveness scale (SRS). We used standardized regression coefficients to measure the effect size. The ASD group exhibited significantly lower urinary TAOC levels and significantly elevated urinary HEL levels than the control group. Urinary 8-OHdG levels and plasma SOD levels were not significantly different between the groups. The ASD group showed significantly higher SRS scores than the control group. Plasma SOD levels correlated significantly with urinary TAOC levels. Standardized regression coefficients revealed that TAOC levels had a larger effect size than HEL levels in urine. This study firstly reveals that an imbalance between urinary HEL and TAOC levels in favor of urinary TAOC levels may contribute to impaired social responsiveness in individuals with ASD. Plasma SOD levels may also affect urinary TAOC levels.

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Acknowledgements

This study was supported by a Grant-in-Aid for Scientific Research on Innovative Areas (Grant No 21200017) (2010-2012) and a Grant-in-Aid for Scientific Research (C) (26461777) (2014-2016) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

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Correspondence to Kunio Yui.

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The present work complied with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans (http://www.wma.net/en/30publications/10policies/b3/index.html). All of the procedures performed in this study were accordance with the ethical standards of the Fujimoto Medical Clinic in Kobe City, Japan. The ethics committee is registered with the Pharmaceuticals and Medical Devices Agency of Japan for IRB information (http://www.info.pmda.go.jp/). Written informed consent was obtained from the participants and/or their parents

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Yui, K., Tanuma, N., Yamada, H. et al. Decreased total antioxidant capacity has a larger effect size than increased oxidant levels in urine in individuals with autism spectrum disorder. Environ Sci Pollut Res 24, 9635–9644 (2017). https://doi.org/10.1007/s11356-017-8595-3

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