Imataka George, Yui Kunio, Shiko Yuki, Kawasaki Yohei, Sasaki Hitomi, Shiroki Ryoichi, Yoshihara Shigemi
Department of Pediatrics, Dokkyo Medical University, Mibu, Japan.
Department of Urology, Fujita Health University, Toyoake, Japan.
Front Psychiatry. 2021 Sep 3;12:684445. doi: 10.3389/fpsyt.2021.684445. eCollection 2021.
The balance between antioxidant capacity and oxidative stress-induced free radicals may be crucial in the pathophysiological development factor of autism spectrum disorder (ASD). We measured the following urinary and plasma biomarker levels of oxidative stress and antioxidants. As urinary biomarkers, (1) hexanoyl-lysine (HEL), which is a new biomarker of oxidative stress, (2) the total antioxidant capacity (TAC), and (3) 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a product of oxidative modifications to DNA; and the plasma levels of (4) the antioxidant protein superoxide dismutase (SOD), which is the crucial defense again oxygen reactive species, and (5) transferrin and (6) ceruloplasmin, which are biomarkers of iron and copper neurotransmission and oxidant-antioxidant systems. We examined the relationship between these urinary and plasma biomarkers and behavioral symptoms in 19 individuals with ASD (mean age, 10.8 ± 5.2 years) and 10 age-matched healthy controls (mean age, 14.2 ± 7.0 years). Behavioral symptoms were estimated using the Aberrant Behavior Checklist (ABC). Urinary TAC levels were significantly lower, whereas urinary HEL levels were significantly increased in the ASD group as compared with the control group. The five ABC subscale and total scores were significantly raised in the autism group than in the control group. The results of a linear regression analysis revealed that plasma SOD levels may be a more accurate predictor of differences in ABC scores between individuals with ASD and control individuals. The present study firstly revealed the important findings that the cooperation between the urinary antioxidant TAC and plasma SOD levels may contribute to the ABC subscale scores of stereotypy. Urinary TAC activity and antioxidant protein SOD may be associated with incomplete mineral body store and antioxidant-related transcription factor and browning reactions. Consequently, a critical imbalance between TAC urinary levels and plasma SOD levels may be an important contributor to autistic behavioral symptoms.
抗氧化能力与氧化应激诱导的自由基之间的平衡可能是自闭症谱系障碍(ASD)病理生理发展因素中的关键因素。我们测量了以下氧化应激和抗氧化剂的尿液及血浆生物标志物水平。作为尿液生物标志物,(1)己酰赖氨酸(HEL),一种新的氧化应激生物标志物;(2)总抗氧化能力(TAC);(3)8-羟基-2'-脱氧鸟苷(8-OHdG),作为DNA氧化修饰的产物;以及血浆中(4)抗氧化蛋白超氧化物歧化酶(SOD)的水平,它是对抗氧活性物质的关键防御物质;(5)转铁蛋白和(6)铜蓝蛋白,它们是铁和铜神经传递以及氧化还原系统的生物标志物。我们研究了19名ASD患者(平均年龄10.8±5.2岁)和10名年龄匹配的健康对照者(平均年龄14.2±7.0岁)的这些尿液和血浆生物标志物与行为症状之间的关系。使用异常行为检查表(ABC)评估行为症状。与对照组相比,ASD组的尿液TAC水平显著降低,而尿液HEL水平显著升高。自闭症组的ABC五个分量表得分和总分均显著高于对照组。线性回归分析结果显示,血浆SOD水平可能是ASD患者与对照个体之间ABC得分差异更准确的预测指标。本研究首次揭示了重要发现,即尿液抗氧化剂TAC与血浆SOD水平之间的协同作用可能导致刻板行为的ABC分量表得分。尿液TAC活性和抗氧化蛋白SOD可能与矿物质储存不完全以及抗氧化相关转录因子和褐变反应有关。因此,TAC尿液水平与血浆SOD水平之间的严重失衡可能是自闭症行为症状的重要促成因素。