Abstract：
Oral ingestion is considered an important route of human exposure to perfluorooctanoic acid (PFOA) and its alternative hexafluoropropylene oxide trimer acid (HFPO-TA). Bioactive compounds are widely used as dietary supplements and food additives. However, little is known about the influence of dietary bioactive compounds on the bioavailability of PFOA and HFPO-TA. Here, three dietary bioactive compounds, β-carotene, quercetin and curcumin, were selected to study their influence on the relative bioavailability (RBA) of PFOA and HFPO-TA in soil using a mouse model. Compared to the control group (68.7 ± 6.27 %), quercetin and curcumin at medium and high doses (20 and 100 mg/kg/d) significantly (p < 0.05) decreased PFOA RBA to 55.2 ± 4.85-56.4 ± 4.57 % and 48.3 ± 5.49-48.6 ± 5.44 %, respectively. Mechanism study showed that medium- and high-dose quercetin as well as high-dose curcumin increased urinary excretion of PFOA by 33.6-35.6 % and 32.2 % through upregulating renal expression of multidrug resistance protein 2 (Mrp2) (1.52-1.63 folds) and Mrp4 (1.26-1.53 folds), thereby reducing PFOA accumulation. In PFOA-treated groups, quercetin at medium and high doses dramatically downregulated the hepatic expression of organic anion transport polypeptides (Oatp1a6, Oatp1b2), organic anion transport proteins (Oat1, Oat2), and fatty acid binding proteins (FABP4, FABP12), while curcumin at medium and high doses inhibited the hepatic expression of Oatp1a6, Oat1 and Oat2. These downregulated genes may reduce the transport of PFOA from blood to liver, and in turn decrease the PFOA RBA. However, β-carotene, quercetin and curcumin exhibited no significant effect on RBA and excretion of HFPO-TA (p > 0.05). This indicated the different absorption mechanisms between PFOA and HFPO-TA, and further research is warranted. This study provided a novel perspective for establishing environmentally friendly ways to reduce health hazards from per- and polyfluoroalkyl substances (PFASs).
摘要：
口服摄入被认为是人类暴露于全氟辛酸（PFOA）及其替代六氟环氧丙烷三聚体酸（HFPO-TA）的重要途径。生物活性化合物广泛用作膳食补充剂和食品添加剂。然而,关于膳食生物活性化合物对PFOA和HFPO-TA生物利用度的影响知之甚少。这里,三种膳食生物活性化合物，β-胡萝卜素,槲皮素和姜黄素,选择小鼠模型来研究它们对土壤中PFOA和HFPO-TA的相对生物利用度（RBA）的影响。与对照组相比(68.7±6.27%),槲皮素和姜黄素在中高剂量（20和100mg/kg/d）显着（p<0.05）使PFOARBA降低至55.2±4.85-56.4±4.57％和48.3±5.49-48.6±5.44％，分别。机制研究表明，中、高剂量槲皮素和高剂量姜黄素通过上调多药耐药蛋白2(Mrp2)(1.52-1.63倍)和Mrp4(1.26-1.53倍)的表达，使PFOA的尿排泄增加了33.6-35.6%和32.2%，从而减少PFOA积累。在PFOA治疗组中，槲皮素在中等和高剂量显著下调有机阴离子转运多肽（Oatp1a6，Oatp1b2）的肝表达，有机阴离子转运蛋白（Oat1，Oat2），和脂肪酸结合蛋白（FABP4，FABP12），而中、高剂量姜黄素抑制Oatp1a6、Oat1和Oat2的肝表达。这些下调的基因可能会减少PFOA从血液到肝脏的转运，进而降低PFOARBA。然而,β-胡萝卜素,槲皮素和姜黄素对RBA和HFPO-TA的排泄无显著影响(p>0.05)。这表明PFOA和HFPO-TA之间的不同吸收机制，需要进一步的研究。这项研究为建立环保方法以减少全氟烷基和多氟烷基物质（PFAS）对健康的危害提供了新的视角。
