Department of Surgery, Rowan University-School of Osteopathic Medicine, Stratford, NJ, United States of America.
Department of Psychiatry, Rowan University-School of Osteopathic Medicine, Stratford, NJ, United States of America.
PLoS One. 2023 Sep 13;18(9):e0289841. doi: 10.1371/journal.pone.0289841. eCollection 2023.
The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.
Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.
We measured the efficiency of glucuronidation in three groups of children, ASD (n = 66), ADHD (n = 46) and healthy controls (CTR, n = 37). The children were recruited from the clinics of Rutgers-NJ Medical School. A urine specimen was collected from each child. Multiple mass spectrometric analyses including the complete metabolome were determined and used to derive values for the efficiency of glucuronidation for 12 varied glucuronidation pathways including those for BPA and MEHP.
(1) Both fold differences and metabolome analyses showed that the three groups of children were metabolically different from each other. (2) Of the 12 pathways examined, only the BPA and DEHP pathways discriminated between the three groups. (3) Glucuronidation efficiencies for BPA were reduced by 11% for ASD (p = 0.020) and 17% for ADHD (p<0.001) compared to controls. DEHP showed similar, but not significant trends.
ASD and ADHD are clinically and metabolically different but share a reduction in the efficiency of detoxification for both BPA and DEHP with the reductions for BPA being statistically significant.
自闭症谱系（ASD）和注意缺陷多动障碍（ADHD）的病因是多因素的。流行病学研究表明，环境污染物如增塑剂与这些疾病之间存在关联。本研究集中研究了这两种化合物中的两种，双酚 A（BPA）和邻苯二甲酸二（2-乙基己基）酯（DEHP）。BPA 和 DEHP 的主要排泄途径是通过葡萄糖醛酸化。葡萄糖醛酸化使不溶性物质更具水溶性，从而允许随后在尿液中排出。
自闭症谱系障碍和注意缺陷多动障碍儿童的这两种增塑剂解毒能力受损。因此，他们的组织更容易接触到这两种增塑剂。
我们测量了三组儿童的葡萄糖醛酸化效率，即自闭症谱系障碍（ASD，n=66）、注意力缺陷多动障碍（ADHD，n=46）和健康对照组（CTR，n=37）。这些儿童是从罗格斯新泽西医学院的诊所招募的。从每个孩子身上采集了一份尿液样本。进行了多种质谱分析，包括完整的代谢组学分析，以得出 12 种不同的葡萄糖醛酸化途径的葡萄糖醛酸化效率值，包括 BPA 和 MEHP。
（1） 倍数差异和代谢组学分析均表明，三组儿童彼此之间存在代谢差异。（2） 在 12 种途径中，只有 BPA 和 DEHP 途径能够区分这三组。（3） 与对照组相比，ASD 儿童的 BPA 葡萄糖醛酸化效率降低了 11%（p=0.020），ADHD 儿童降低了 17%（p<0.001）。DEHP 显示出类似但不显著的趋势。
自闭症谱系障碍和注意缺陷多动障碍在临床上和代谢上存在差异，但它们都存在 BPA 和 DEHP 解毒效率降低的情况，其中 BPA 的降低具有统计学意义。
