血清代谢组学研究长期低剂量PFOS暴露对大鼠的毒性效应

华炜桢, 吴衍, 黄清育. 血清代谢组学研究长期低剂量PFOS暴露对大鼠的毒性效应[J]. 生态毒理学报, 2023, 18(4): 349-359. doi: 10.7524/AJE.1673-5897.20221109001
引用本文: 华炜桢, 吴衍, 黄清育. 血清代谢组学研究长期低剂量PFOS暴露对大鼠的毒性效应[J]. 生态毒理学报, 2023, 18(4): 349-359. doi: 10.7524/AJE.1673-5897.20221109001
Hua Weizhen, Wu Yan, Huang Qingyu. Serum Metabolomics Analysis Reveals Toxicity Induced by Long Term Low-Dose PFOS Exposure in Rats[J]. Asian journal of ecotoxicology, 2023, 18(4): 349-359. doi: 10.7524/AJE.1673-5897.20221109001
Citation: Hua Weizhen, Wu Yan, Huang Qingyu. Serum Metabolomics Analysis Reveals Toxicity Induced by Long Term Low-Dose PFOS Exposure in Rats[J]. Asian journal of ecotoxicology, 2023, 18(4): 349-359. doi: 10.7524/AJE.1673-5897.20221109001

血清代谢组学研究长期低剂量PFOS暴露对大鼠的毒性效应

    作者简介: 华炜桢(1999-),男,硕士研究生,研究方向为代谢组学,E-mail:wzhua@fjmu.edu.cn
    通讯作者: 吴衍,E-mail:yanwu@fjmu.edu.cn;  黄清育,E-mail:qyhuang@iue.ac.cn
  • 基金项目:

    国家自然科学基金资助项目(22076179,21677142);福建省自然科学基金资助项目(2022J06033);厦门市青年创新基金资助项目(3502Z20206091)

  • 中图分类号: X171.5

Serum Metabolomics Analysis Reveals Toxicity Induced by Long Term Low-Dose PFOS Exposure in Rats

    Corresponding authors: Wu Yan ;  Huang Qingyu
  • Fund Project:
  • 摘要: 全氟辛烷磺酸(perfluorooctane sulfonate, PFOS)是一种具有高生物蓄积性的持久性有机污染物,其环境暴露与多种不良健康效应有关。然而,慢性低剂量PFOS暴露对机体代谢网络的影响目前尚不清楚。本研究将大鼠暴露于0.015、0.15、1.5 mg·kg-1的PFOS 2个月后,采用超高效液相色谱-质谱联用法(UPLC-MS)分析其血清代谢组,并比较暴露组与对照组的代谢谱差异,筛选差异代谢物及相关代谢通路。结果显示,暴露后大鼠血清中的PFOS含量随暴露剂量的增大显著上升,说明PFOS可在大鼠体内蓄积。此外,在各暴露组中共筛选出9种共同差异代谢物,其中5种代谢物在PFOS暴露后含量降低,4种代谢物水平上升。这些差异代谢物主要涉及脂质代谢和嘌呤代谢等代谢途径。所有单一代谢物的ROC曲线下面积(AUC)均>0.8,7种以上(含7种)代谢物组合时的AUC为1,表明这些代谢标志物对于PFOS暴露具有较高的判别能力。本研究结果可为环境低剂量PFOS暴露的健康风险评估及毒性机制解析提供一定的参考依据。
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  • Boyles A L, Blain R B, Rochester J R, et al. Systematic review of community health impacts of mountaintop removal mining[J]. Environment International, 2017, 107:163-172
    Paul A G, Jones K C, Sweetman A J. A first global production, emission, and environmental inventory for perfluorooctane sulfonate[J]. Environmental Science & Technology, 2009, 43(2):386-392
    Wang T, Wang Y W, Liao C Y, et al. Perspectives on the inclusion of perfluorooctane sulfonate into the Stockholm Convention on persistent organic pollutants[J]. Environmental Science & Technology, 2009, 43(14):5171-5175
    中华人民共和国生态环境部. 重点管控新污染物清单(2021年版)[R]. 北京:中华人民共和国生态环境部, 2021
    Peden-Adams M M, Stuckey J E, Gaworecki K M, et al. Developmental toxicity in white leghorn chickens following in ovo exposure to perfluorooctane sulfonate (PFOS)[J]. Reproductive Toxicology, 2009, 27(3-4):307-318
    Kennedy G L Jr, Butenhoff J L, Olsen G W, et al. The toxicology of perfluorooctanoate[J]. Critical Reviews in Toxicology, 2004, 34(4):351-384
    Betts K S. Perfluoroalkyl acids:What is the evidence telling us?[J]. Environmental Health Perspectives, 2007, 115(5):A250-A256
    Lin C Y, Chen P C, Lin Y C, et al. Association among serum perfluoroalkyl chemicals, glucose homeostasis, and metabolic syndrome in adolescents and adults[J]. Diabetes Care, 2009, 32(4):702-707
    Liu H S, Wen L L, Chu P L, et al. Association among total serum isomers of perfluorinated chemicals, glucose homeostasis, lipid profiles, serum protein and metabolic syndrome in adults:NHANES, 2013-2014[J]. Environmental Pollution, 2018, 232:73-79
    Cardenas A, Gold D R, Hauser R, et al. Plasma concentrations of per- and polyfluoroalkyl substances at baseline and associations with glycemic indicators and diabetes incidence among high-risk adults in the diabetes prevention program trial[J]. Environmental Health Perspectives, 2017, 125(10):107001
    Cakmak S, Lukina A, Karthikeyan S, et al. The association between blood PFAS concentrations and clinical biochemical measures of organ function and metabolism in participants of the Canadian Health Measures Survey (CHMS)[J]. The Science of the Total Environment, 2022, 827:153900
    Chen A M, Jandarov R, Zhou L, et al. Association of perfluoroalkyl substances exposure with cardiometabolic traits in an island population of the eastern Adriatic Coast of Croatia[J]. The Science of the Total Environment, 2019, 683:29-36
    Behr A C, Kwiatkowski A, Ståhlman M, et al. Impairment of bile acid metabolism by perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in human HepaRG hepatoma cells[J]. Archives of Toxicology, 2020, 94(5):1673-1686
    Cui Y, Lv S, Liu J, et al. Chronic perfluorooctanesulfonic acid exposure disrupts lipid metabolism in zebrafish[J]. Human & Experimental Toxicology, 2017, 36(3):207-217
    Yi S J, Chen P Y, Yang L P, et al. Probing the hepatotoxicity mechanisms of novel chlorinated polyfluoroalkyl sulfonates to zebrafish larvae:Implication of structural specificity[J]. Environment International, 2019, 133(Pt B):105262
    Johnson C H, Ivanisevic J, Siuzdak G. Metabolomics:Beyond biomarkers and towards mechanisms[J]. Nature Reviews Molecular Cell Biology, 2016, 17(7):451-459
    Zhang L B, Sun W, Chen H G, et al. Transcriptome analysis of acute exposure of the Manila clam, Ruditapes philippinarum to perfluorooctane sulfonate (PFOS)[J]. Comparative Biochemistry and Physiology Toxicology & Pharmacology, 2020, 231:108736
    Ortiz-Villanueva E, Jaumot J, Martínez R, et al. Assessment of endocrine disruptors effects on zebrafish (Danio rerio) embryos by untargeted LC-HRMS metabolomic analysis[J]. The Science of the Total Environment, 2018, 635:156-166
    Beale D J, Hillyer K, Nilsson S, et al. Bioaccumulation and metabolic response of PFAS mixtures in wild-caught freshwater turtles (Emydura macquarii macquarii) using omics-based ecosurveillance techniques[J]. The Science of the Total Environment, 2022, 806(Pt 3):151264
    Oakes K D, Sibley P K, Martin J W, et al. Short-term exposures of fish to perfluorooctane sulfonate:Acute effects on fatty acyl-coa oxidase activity, oxidative stress, and circulating sex steroids[J]. Environmental Toxicology and Chemistry, 2005, 24(5):1172-1181
    Zhang L M, Rimal B, Nichols R G, et al. Perfluorooctane sulfonate alters gut microbiota-host metabolic homeostasis in mice[J]. Toxicology, 2020, 431:152365
    Deng P, Durham J, Liu J P, et al. Metabolomic, lipidomic, transcriptomic, and metagenomic analyses in mice exposed to PFOS and fed soluble and insoluble dietary fibers[J]. Environmental Health Perspectives, 2022, 130(11):117003
    Li Z J, Lin Z Y, Ji S Q, et al. Perfluorooctanesulfonic acid exposure altered hypothalamic metabolism and disturbed male fecundity[J]. The Science of the Total Environment, 2022, 844:156881
    Jin Y H, Liu W, Sato I, et al. PFOS and PFOA in environmental and tap water in China[J]. Chemosphere, 2009, 77(5):605-611
    Zareitalabad P, Siemens J, Hamer M, et al. Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in surface waters, sediments, soils and wastewater-A review on concentrations and distribution coefficients[J]. Chemosphere, 2013, 91(6):725-732
    Benford D, Boer J, Carere A, et al. Opinion of the Scientific Panel on contaminants in the food chain on perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and their salts[J]. EFSA Journal, 2008, 653:1-131
    Kell D B, Brown M, Davey H M, et al. Metabolic footprinting and systems biology:The medium is the message[J]. Nature Reviews Microbiology, 2005, 3(7):557-565
    Wang X J, Sun H, Zhang A H, et al. Potential role of metabolomics apporoaches in the area of traditional Chinese medicine:As pillars of the bridge between Chinese and Western medicine[J]. Journal of Pharmaceutical and Biomedical Analysis, 2011, 55(5):859-868
    Winder C L, Cornmell R, Schuler S, et al. Metabolic fingerprinting as a tool to monitor whole-cell biotransformations[J]. Analytical and Bioanalytical Chemistry, 2011, 399(1):387-401
    Zhang A H, Sun H, Wang P, et al. Future perspectives of personalized medicine in traditional Chinese medicine:A systems biology approach[J]. Complementary Therapies in Medicine, 2012, 20(1-2):93-99
    Nair A B, Jacob S. A simple practice guide for dose conversion between animals and human[J]. Journal of Basic and Clinical Pharmacy, 2016, 7(2):27-31
    Alam M N, Han X, Nan B R, et al. Chronic low-level perfluorooctane sulfonate (PFOS) exposure promotes testicular steroidogenesis through enhanced histone acetylation[J]. Environmental Pollution, 2021, 284:117518
    Forsthuber M, Kaiser A M, Granitzer S, et al. Albumin is the major carrier protein for PFOS, PFOA, PFHxS, PFNA and PFDA in human plasma[J]. Environment International, 2020, 137:105324
    Olsen G W, Burris J M, Ehresman D J, et al. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers[J]. Environmental Health Perspectives, 2007, 115(9):1298-1305
    Austin M E, Kasturi B S, Barber M, et al. Neuroendocrine effects of perfluorooctane sulfonate in rats[J]. Environmental Health Perspectives, 2003, 111(12):1485-1489
    Chang S C, Thibodeaux J R, Eastvold M L, et al. Negative bias from analog methods used in the analysis of free thyroxine in rat serum containing perfluorooctanesulfonate (PFOS)[J]. Toxicology, 2007, 234(1-2):21-33
    Conley J M, Lambright C S, Evans N, et al. Developmental toxicity of Nafion byproduct 2(NBP2) in the Sprague-Dawley rat with comparisons to hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) and perfluorooctane sulfonate (PFOS)[J]. Environment International, 2022, 160:107056
    Jin R, McConnell R, Catherine C, et al. Perfluoroalkyl substances and severity of nonalcoholic fatty liver in children:An untargeted metabolomics approach[J]. Environment International, 2020, 134:105220
    Hu X, Li S Z, Cirillo P M, et al. Reprint of "metabolome wide association study of serum poly and perfluoroalkyl substances (PFASs) in pregnancy and early postpartum"[J]. Reproductive Toxicology, 2020, 92:120-128
    Alderete T L, Jin R, Walker D I, et al. Perfluoroalkyl substances, metabolomic profiling, and alterations in glucose homeostasis among overweight and obese Hispanic children:A proof-of-concept analysis[J]. Environment International, 2019, 126:445-453
    Huang Q Y, Hu D Y, Wang X F, et al. The modification of indoor PM2.5 exposure to chronic obstructive pulmonary disease in Chinese elderly people:A meet-in-metabolite analysis[J]. Environment International, 2018, 121(Pt 2):1243-1252
    Zhang J, Mu X L, Xia Y K, et al. Metabolomic analysis reveals a unique urinary pattern in normozoospermic infertile men[J]. Journal of Proteome Research, 2014, 13(6):3088-3099
    Steenland K, Tinker S, Frisbee S, et al. Association of perfluorooctanoic acid and perfluorooctane sulfonate with serum lipids among adults living near a chemical plant[J]. American Journal of Epidemiology, 2009, 170(10):1268-1278
    Wan H T, Zhao Y G, Wei X, et al. PFOS-induced hepatic steatosis, the mechanistic actions on β-oxidation and lipid transport[J]. Biochimica et Biophysica Acta, 2012, 1820(7):1092-1101
    Imes C C, Austin M A. Low-density lipoprotein cholesterol, apolipoprotein B, and risk of coronary heart disease:From familial hyperlipidemia to genomics[J]. Biological Research for Nursing, 2013, 15(3):292-308
    Li Y, Barregard L, Xu Y Y, et al. Associations between perfluoroalkyl substances and serum lipids in a Swedish adult population with contaminated drinking water[J]. Environmental Health:A Global Access Science Source, 2020, 19(1):33
    Bijland S, Rensen P C, Pieterman E J, et al. Perfluoroalkyl sulfonates cause alkyl chain length-dependent hepatic steatosis and hypolipidemia mainly by impairing lipoprotein production in APOE*3-Leiden CETP mice[J]. Toxicological Sciences:An Official Journal of the Society of Toxicology, 2011, 123(1):290-303
    Cheng J F, Lv S P, Nie S F, et al. Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish[J]. Aquatic Toxicology, 2016, 176:45-52
    Martínez R, Navarro-Martín L, Luccarelli C, et al. Unravelling the mechanisms of PFOS toxicity by combining morphological and transcriptomic analyses in zebrafish embryos[J]. The Science of the Total Environment, 2019, 674:462-471
    Fragki S, Dirven H, Fletcher T, et al. Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans:What do we know and what not?[J]. Critical Reviews in Toxicology, 2021, 51(2):141-164
    Chen P, Goldberg D E, Kolb B, et al. Inosine induces axonal rewiring and improves behavioral outcome after stroke[J]. Proceedings of the National Academy of Sciences of the United States of America, 2002, 99(13):9031-9036
    Yegutkin G G, Samburski S S, Jalkanen S. Soluble purine-converting enzymes circulate in human blood and regulate extracellular ATP level via counteracting pyrophosphatase and phosphotransfer reactions[J]. FASEB Journal:Official Publication of the Federation of American Societies for Experimental Biology, 2003, 17(10):1328-1330
    Gong X, Yang C X, Hong Y J, et al. PFOA and PFOS promote diabetic renal injury in vitro by impairing the metabolisms of amino acids and purines[J]. The Science of the Total Environment, 2019, 676:72-86
    Jiang L L, Hong Y J, Xie G S, et al. Comprehensive multi-omics approaches reveal the hepatotoxic mechanism of perfluorohexanoic acid (PFHxA) in mice[J]. The Science of the Total Environment, 2021, 790:148160
    Ni X L, Hu G H, Cai X. The success and the challenge of all-trans retinoic acid in the treatment of cancer[J]. Critical Reviews in Food Science and Nutrition, 2019, 59(sup1):S71-S80
    Li Y Q, Lu X Y, Yu N Y, et al. Exposure to legacy and novel perfluoroalkyl substance disturbs the metabolic homeostasis in pregnant women and fetuses:A metabolome-wide association study[J]. Environment International, 2021, 156:106627
    Li C H, Jiang L D, Qi Y, et al. Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes[J]. Ecotoxicology and Environmental Safety, 2023, 249:114361
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  • 收稿日期:  2022-11-09
华炜桢, 吴衍, 黄清育. 血清代谢组学研究长期低剂量PFOS暴露对大鼠的毒性效应[J]. 生态毒理学报, 2023, 18(4): 349-359. doi: 10.7524/AJE.1673-5897.20221109001
引用本文: 华炜桢, 吴衍, 黄清育. 血清代谢组学研究长期低剂量PFOS暴露对大鼠的毒性效应[J]. 生态毒理学报, 2023, 18(4): 349-359. doi: 10.7524/AJE.1673-5897.20221109001
Hua Weizhen, Wu Yan, Huang Qingyu. Serum Metabolomics Analysis Reveals Toxicity Induced by Long Term Low-Dose PFOS Exposure in Rats[J]. Asian journal of ecotoxicology, 2023, 18(4): 349-359. doi: 10.7524/AJE.1673-5897.20221109001
Citation: Hua Weizhen, Wu Yan, Huang Qingyu. Serum Metabolomics Analysis Reveals Toxicity Induced by Long Term Low-Dose PFOS Exposure in Rats[J]. Asian journal of ecotoxicology, 2023, 18(4): 349-359. doi: 10.7524/AJE.1673-5897.20221109001

血清代谢组学研究长期低剂量PFOS暴露对大鼠的毒性效应

    通讯作者: 吴衍,E-mail:yanwu@fjmu.edu.cn;  黄清育,E-mail:qyhuang@iue.ac.cn
    作者简介: 华炜桢(1999-),男,硕士研究生,研究方向为代谢组学,E-mail:wzhua@fjmu.edu.cn
  • 1. 福建医科大学公共卫生学院卫生检验与检疫学系, 福州 350122;
  • 2. 中国科学院城市环境研究所, 城市环境与健康重点实验室, 厦门 361021
基金项目:

国家自然科学基金资助项目(22076179,21677142);福建省自然科学基金资助项目(2022J06033);厦门市青年创新基金资助项目(3502Z20206091)

摘要: 全氟辛烷磺酸(perfluorooctane sulfonate, PFOS)是一种具有高生物蓄积性的持久性有机污染物,其环境暴露与多种不良健康效应有关。然而,慢性低剂量PFOS暴露对机体代谢网络的影响目前尚不清楚。本研究将大鼠暴露于0.015、0.15、1.5 mg·kg-1的PFOS 2个月后,采用超高效液相色谱-质谱联用法(UPLC-MS)分析其血清代谢组,并比较暴露组与对照组的代谢谱差异,筛选差异代谢物及相关代谢通路。结果显示,暴露后大鼠血清中的PFOS含量随暴露剂量的增大显著上升,说明PFOS可在大鼠体内蓄积。此外,在各暴露组中共筛选出9种共同差异代谢物,其中5种代谢物在PFOS暴露后含量降低,4种代谢物水平上升。这些差异代谢物主要涉及脂质代谢和嘌呤代谢等代谢途径。所有单一代谢物的ROC曲线下面积(AUC)均>0.8,7种以上(含7种)代谢物组合时的AUC为1,表明这些代谢标志物对于PFOS暴露具有较高的判别能力。本研究结果可为环境低剂量PFOS暴露的健康风险评估及毒性机制解析提供一定的参考依据。

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