Institute of Environmental Health Sciences and Department of Pharmacology, Wayne State University, Detroit, MI 48202, USA.
Genome Sciences Core, Wayne State University, Detroit, MI 48202, USA.
Endocrinology. 2024 Oct 30;165(12). doi: 10.1210/endocr/bqae149.
Surfactants are molecules with both hydrophobic and hydrophilic structural groups that adsorb at the air-water or oil-water interface and serve to decrease the surface tension. Surfactants combine to form micelles that surround and break down or remove oils, making them ideal for detergents and cleaners. Two of the most important classes of nonionic surfactants are alkylphenol ethoxylates (APEOs) and alcohol ethoxylates (AEOs). APEOs and AEOs are high production-volume chemicals that are used for many industrial and residential purposes, including laundry detergents, hard-surface cleaners, paints, and pesticide adjuvants. Commensurate with better appreciation of the toxicity of APEOs and the base alkylphenols, use of AEOs has increased, and both sets of compounds are now ubiquitous environmental contaminants. We recently demonstrated that diverse APEOs and AEOs induce triglyceride accumulation and/or preadipocyte proliferation in vitro. Both sets of contaminants have also been demonstrated as obesogenic and metabolism-disrupting in a developmental exposure zebrafish model. While these metabolic health effects are consistent across models and species, the mechanisms underlying these effects are less clear. This study sought to evaluate causal mechanisms through reporter gene assays, relative binding affinity assays, coexposure experiments, and use of both human cell and zebrafish models. We report that antagonism of thyroid hormone receptor signaling appears to mediate at least a portion of the polyethoxylate-induced metabolic health effects. These results suggest further evaluation is needed, given the ubiquitous environmental presence of these thyroid-disrupting contaminants and reproducible effects in human cell models and vertebrate animals.
表面活性剂是具有疏水和亲水结构基团的分子，它们在气-水或油-水界面上吸附，从而降低表面张力。表面活性剂结合形成胶束，包围并分解或去除油，使其成为理想的洗涤剂和清洁剂。非离子表面活性剂中最重要的两类是烷基酚聚氧乙烯醚 (APEOs) 和脂肪醇聚氧乙烯醚 (AEOs)。APEOs 和 AEOs 是高产量的化学品，用于许多工业和住宅用途，包括洗衣洗涤剂、硬表面清洁剂、油漆和农药助剂。由于人们对 APEOs 和基础烷基酚的毒性有了更好的认识，AEOs 的使用增加了，这两种化合物现在都是普遍存在的环境污染物。我们最近证明，不同的 APEOs 和 AEOs 在体外诱导甘油三酯积累和/或前脂肪细胞增殖。这两组污染物也被证明在发育暴露的斑马鱼模型中具有肥胖和代谢紊乱的作用。虽然这些代谢健康影响在模型和物种之间是一致的，但这些影响的机制尚不清楚。本研究通过报告基因检测、相对结合亲和力检测、共暴露实验以及使用人源细胞和斑马鱼模型，试图评估因果机制。我们报告说，甲状腺激素受体信号的拮抗作用似乎至少介导了部分聚氧乙烯诱导的代谢健康影响。鉴于这些破坏甲状腺的污染物在环境中无处不在，并且在人源细胞模型和脊椎动物中具有可重复的影响，这些结果表明需要进一步评估。
