Yui Kunio, Tanuma Nasoyuki, Yamada Hiroshi, Kawasaki Yohei
Department of Pediatrics, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan.
Department of Drug Evaluation and Informatics, School of Pharmaceutical Science, University of Shizuoka, Shizuoka, 422-8526, Japan.
Environ Sci Pollut Res Int. 2017 Apr;24(10):9635-9644. doi: 10.1007/s11356-017-8595-3. Epub 2017 Mar 1.
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.
氧化应激/抗氧化失衡可能与自闭症谱系障碍（ASD）的病理生理机制有关。我们检测了尿液中与氧化应激相关的生物标志物己酰赖氨酸（HEL）、总抗氧化能力（TAOC）、DNA甲基化生物标志物8-羟基-2'-脱氧鸟苷（8-OHdG）的水平，以及主要抗氧化酶超氧化物歧化酶（SOD）的血浆水平。我们研究了这四种生物标志物与20名自闭症谱系障碍患者和11名健康对照者的社会反应性之间的关系。两组之间的性别分布（自闭症谱系障碍组，7/13；对照组，4/7）和年龄分布（自闭症谱系障碍组，10.7±5.0岁；对照组，14.7±6.3岁）无显著差异。使用社会反应量表（SRS）评估社会反应性。我们使用标准化回归系数来衡量效应大小。与对照组相比，自闭症谱系障碍组的尿液TAOC水平显著降低，尿液HEL水平显著升高。两组之间的尿液8-OHdG水平和血浆SOD水平无显著差异。自闭症谱系障碍组的SRS得分显著高于对照组。血浆SOD水平与尿液TAOC水平显著相关。标准化回归系数显示，尿液中TAOC水平的效应大小比HEL水平更大。本研究首次揭示，尿液中HEL和TAOC水平失衡，有利于尿液TAOC水平，可能导致自闭症谱系障碍患者的社会反应受损。血浆SOD水平也可能影响尿液TAOC水平。
