Department of Biology, University of North Texas, Denton, TX 76203, USA.
Department of Marine Biology, Texas A&M at Galveston, Galveston, TX 77554, USA.
Int J Mol Sci. 2021 Dec 16;22(24):13489. doi: 10.3390/ijms222413489.
Di(2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in various industrial and household plastic products, ensuring widespread human exposures. Its routine detection in human bio-fluids and the propensity of its monoester metabolite to activate peroxisome proliferator activated receptor-α (PPARα) and perturb lipid metabolism implicate it as a metabolic disrupter. In this study we evaluated the effects of DEHP exposure on hepatic levels of free CoA and various CoA esters, while also confirming the metabolic activation to CoA esters and partial β-oxidation of a DEHP metabolite (2-ethyhexanol). Male Wistar rats were exposed via diet to 2% (/) DEHP for fourteen-days, following which hepatic levels of free CoA and various CoA esters were identified using liquid chromatography-mass spectrometry. DEHP exposed rats showed significantly elevated free CoA and increased levels of physiological, DEHP-derived and unidentified CoA esters. The physiological CoA ester of malonyl-CoA and DEHP-derived CoA ester of 3-keto-2-ethylhexanoyl-CoA were the most highly elevated, at eighteen- and ninety eight-times respectively. We also detected sixteen unidentified CoA esters which may be derivative of DEHP metabolism or induction of other intermediary metabolism metabolites. Our results demonstrate that DEHP is a metabolic disrupter which affects production and sequestration of CoA, an essential cofactor of oxidative and biosynthetic reactions.
邻苯二甲酸二（2-乙基己基）酯（DEHP）常用于各种工业和家用塑料制品的增塑剂，确保了广泛的人体暴露。其在人体生物流体中的常规检测及其单酯代谢物激活过氧化物酶体增殖物激活受体-α（PPARα）和扰乱脂质代谢的倾向表明其为代谢干扰物。在这项研究中，我们评估了 DEHP 暴露对肝内游离 CoA 和各种 CoA 酯水平的影响，同时还证实了 DEHP 代谢物（2-乙基己醇）向 CoA 酯的代谢激活和部分β-氧化。雄性 Wistar 大鼠通过饮食暴露于 2%（/）DEHP 14 天，然后使用液相色谱-质谱法鉴定肝内游离 CoA 和各种 CoA 酯的水平。暴露于 DEHP 的大鼠表现出游离 CoA 显著升高和生理、DEHP 衍生和未鉴定的 CoA 酯水平升高。生理 CoA 酯的丙二酰 CoA 和 DEHP 衍生的 CoA 酯的 3-酮-2-乙基己酰 CoA 分别升高了 18 倍和 98 倍。我们还检测到 16 种未鉴定的 CoA 酯，可能是 DEHP 代谢物或其他中间代谢物诱导的衍生物。我们的结果表明，DEHP 是一种代谢干扰物，影响 CoA 的产生和隔离，CoA 是氧化和生物合成反应的必需辅酶。
