增塑剂DEHP神经毒性作用及机制的研究进展
Research Progress on Neurotoxic Effects and Mechanism of Plasticizer DEHP
-
摘要: 近年来，增塑剂邻苯二甲酸二(2-乙基己)酯(di-(2-ethylhexyl) phthalate, DEHP)的神经毒性作用越来越受到人们的关注。DEHP可通过多种途径进入脑组织并作用于中枢神经系统，导致各种损伤。因此，笔者系统阐述DEHP进入脑组织的途径、神经毒性作用表现及其机制，为今后深入研究DEHP的健康效应及分子机制，制定更为合理的、针对不同暴露人群的安全限值和暴露限值提供理论参考。
-
关键词:
- 邻苯二甲酸二(2-乙基己)酯 /
- 神经毒性 /
- 阿尔茨海默症
Abstract: In recent years, the neurotoxicity of the plasticizer di-(2-ethylhexyl) phthalate (DEHP) has attracted more and more attention. DEHP can enter the brain tissue through a variety of routes and act on the central nervous system, causing various injuries. Therefore, this review systematically elucidates the ways that DEHP enters the brain tissue, its neurotoxic effects and underlying mechanisms so as to provide recommendations for future research on the health effects and molecular mechanisms of DEHP, and also to provide references to develop more reasonable safety and exposure limits for different exposed groups.-
Key words:
- bis(2-ethylhexyl) phthalate /
- neurotoxicity /
- Alzheimer’s disease
-
-
Schettler T. Human exposure to phthalates via consumer products [J]. International Journal of Andrology, 2006, 29(1): 134-139 Ting K C, Gill M, Garbin O. GC/MS screening method for phthalate esters in children’s toys [J]. Journal of AOAC International, 2019, 92(3): 951-958 Lai J P, Yang M L, Niessner R, et al. Molecularly imprinted microspheres and nanospheres for di(2-ethylhexyl)phthalate prepared by precipitation polymerization [J]. Analytical and Bioanalytical Chemistry, 2007, 389(2): 405-412 Fierens T, Servaes K, Holderbeke M V, et al. Analysis of phthalates in food products and packaging materials sold on the Belgian market [J]. Food and Chemical Toxicology, 2012, 50(7): 2575-2583 Kavlock R, Boekelheide K, Chapin R, et al. NTP Center for the Evaluation of Risks to Human Reproduction: Phthalates expert panel report on the reproductive and developmental toxicity of di(2-ethylhexyl) phthalate [J]. Reproductive Toxicology, 2002, 16(5): 529-653 Doull J, Cattley R, Elcombe C, et al. A cancer risk assessment of di(2-ethylhexyl)phthalate: Application of the new US EPA risk assessment guidelines [J]. Regulatory Toxicology and Pharmacology, 1999, 29(3): 327-357 Steiner I, Scharf L, Fiala F, et al. Migration of di-(2-ethylhexyl) phthalate from PVC child articles into saliva and saliva simulant [J]. Food Additives & Contaminants, 1998, 15(7): 812-817 Serrano S E, Braun J, Trasande L, et al. Phthalates and diet: A review of the food monitoring and epidemiology data [J]. Environmental Health: A Global Access Science Source, 2014, 13(1): 43 den Braver-Sewradj S P, Piersma A, Hessel E V S. An update on the hazard of and exposure to diethyl hexyl phthalate (DEHP) alternatives used in medical devices [J]. Critical Reviews in Toxicology, 2020, 50(8): 650-672 Villanger G D, Drover S S M, Nethery R C, et al. Associations between urine phthalate metabolites and thyroid function in pregnant women and the influence of iodine status [J]. Environment International, 2020, 137: 105509 Mallow E B, Fox M A. Phthalates and critically ill neonates: Device-related exposures and non-endocrine toxic risks [J]. Journal of Perinatology: Official Journal of the California Perinatal Association, 2014, 34(12): 892-897 Beg M A, Sheikh I A. Endocrine disruption: Structural interactions of androgen receptor against di(2-ethylhexyl) phthalate and its metabolites [J]. Toxics, 2020, 8(4): 115 Tassinari R, Tait S, Busani L, et al. Metabolic, reproductive and thyroid effects of bis(2-ethylhexyl) phthalate (DEHP) orally administered to male and female juvenile rats at dose levels derived from children biomonitoring study [J]. Toxicology, 2021, 449: 152653 Yu L L, Yang M, Cheng M, et al. Associations between urinary phthalate metabolite concentrations and markers of liver injury in the US adult population [J]. Environment International, 2021, 155: 106608 Ramadan M, Cooper B, Posnack N G. Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes [J]. Birth Defects Research, 2020, 112(17): 1362-1385 Gaynor J W, Ittenbach R F, Calafat A M, et al. Perioperative exposure to suspect neurotoxicants from medical devices in newborns with congenital heart defects [J]. The Annals of Thoracic Surgery, 2019, 107(2): 567-572 Li J F, Qian X, Zhou Y Q, et al. Trimester-specific and sex-specific effects of prenatal exposure to di(2-ethylhexyl) phthalate on fetal growth, birth size, and early-childhood growth: A longitudinal prospective cohort study [J]. The Science of the Total Environment, 2021, 777: 146146 Al-Saleh I, Elkhatib R, Alrushud N, et al. Potential health risks of maternal phthalate exposure during the first trimester: The Saudi Early Autism and Environment Study (SEAES) [J]. Environmental Research, 2021, 195: 110882 Watkins D J, Meeker J D, Tamayo-Ortiz M, et al. Gestational and peripubertal phthalate exposure in relation to attention performance in childhood and adolescence [J]. Environmental Research, 2021, 196: 110911 Mesnil M, Defamie N, Naus C, et al. Brain disorders and chemical pollutants: A gap junction link? [J]. Biomolecules, 2020, 11(1): 51 Stroustrup A, Bragg J B, Andra S S, et al. Neonatal intensive care unit phthalate exposure and preterm infant neurobehavioral performance [J]. PLoS One, 2018, 13(3): e0193835 Ahmadpour D, Mhaouty-Kodja S, Grange-Messent V. Disruption of the blood-brain barrier and its close environment following adult exposure to low doses of di(2-ethylhexyl)phthalate alone or in an environmental phthalate mixture in male mice [J]. Chemosphere, 2021, 282: 131013 Choi G, Keil A P, Richardson D B, et al. Pregnancy exposure to organophosphate esters and the risk of attention-deficit hyperactivity disorder in the Norwegian mother, father and child cohort study [J]. Environment International, 2021, 154: 106549 Dong J, Fu H, Fu Y Y, et al. Maternal exposure to di-(2-ethylhexyl) phthalate impairs hippocampal synaptic plasticity in male offspring: Involvement of damage to dendritic spine development [J]. ACS Chemical Neuroscience, 2021, 12(2): 311-322 Ran D Z, Luo Y, Gan Z J, et al. Neural mechanisms underlying the deficit of learning and memory by exposure to di(2-ethylhexyl) phthalate in rats [J]. Ecotoxicology and Environmental Safety, 2019, 174: 58-65 Minatoya M, Kishi R. A review of recent studies on bisphenol A and phthalate exposures and child neurodevelopment [J]. International Journal of Environmental Research and Public Health, 2021, 18(7): 3585 Nadeem A, Ahmad S F, Al-Harbi N O, et al. Ubiquitous plasticizer, di-(2-ethylhexyl) phthalate enhances existing inflammatory profile in monocytes of children with autism [J]. Toxicology, 2020, 446: 152597 Singh A R, Lawrence W H, Autianx J. Maternal-fetal transfer of 14C-di-2-ethylhexyl phthalate and 14C-diethyl phthalate in rats [J]. Journal of Pharmaceutical Sciences, 1975, 64(8): 1347-1350 Lin H, Yuan K M, Li L Y, et al. In utero exposure to diethylhexyl phthalate affects rat brain development: A behavioral and genomic approach [J]. International Journal of Environmental Research and Public Health, 2015, 12(11): 13696-13710 Jankowska A, Polańska K, Koch H M, et al. Phthalate exposure and neurodevelopmental outcomes in early school age children from Poland [J]. Environmental Research, 2019, 179(Pt B): 108829 Qian X, Li J F, Xu S Q, et al. Prenatal exposure to phthalates and neurocognitive development in children at two years of age [J]. Environment International, 2019, 131: 105023 Chakraborty R, Vijay Kumar M J, Clement J P. Critical aspects of neurodevelopment [J]. Neurobiology of Learning and Memory, 2021, 180: 107415 Liu S H, Bobb J F, Lee K H, et al. Lagged kernel machine regression for identifying time windows of susceptibility to exposures of complex mixtures [J]. Biostatistics, 2018, 19(3): 325-341 Lei M, Menon R, Manteiga S, et al. Environmental chemical diethylhexyl phthalate alters intestinal microbiota community structure and metabolite profile in mice [J]. mSystems, 2019, 4(6): e00724-e00719 Martínez-Razo L D, Martínez-Ibarra A, Vázquez-Martínez E R, et al. The impact of di-(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate in placental development, function, and pathophysiology [J]. Environment International, 2021, 146: 106228 Shen R, Zhao L L, Yu Z, et al. Maternal di-(2-ethylhexyl) phthalate exposure during pregnancy causes fetal growth restriction in a stage-specific but gender-independent manner [J]. Reproductive Toxicology, 2017, 67: 117-124 Luo B B, Feng Q W, Wu D J, et al. Experimental study on DEHP affect the neurodevelopment through interfering with placental thyroid hormones transport [J]. Chinese Journal of Industrial Hygiene and Occupational Diseases, 2018, 36(3): 179-183 Yu Z, Han Y, Shen R, et al. Gestational di-(2-ethylhexyl) phthalate exposure causes fetal intrauterine growth restriction through disturbing placental thyroid hormone receptor signaling [J]. Toxicology Letters, 2018, 294: 1-10 Dhanya C R, Indu A R, Deepadevi K V, et al. Inhibition of membrane Na(+)-K+ Atpase of the brain, liver and RBC in rats administered di(2-ethyl hexyl) phthalate (DEHP) a plasticizer used in polyvinyl chloride (PVC) blood storage bags [J]. Indian Journal of Experimental Biology, 2003, 41(8): 814-820 Tanida T, Warita K, Ishihara K, et al. Fetal and neonatal exposure to three typical environmental chemicals with different mechanisms of action: Mixed exposure to phenol, phthalate, and dioxin cancels the effects of sole exposure on mouse midbrain dopaminergic nuclei [J]. Toxicology Letters, 2009, 189(1): 40-47 Komada M, Gendai Y, Kagawa N, et al. Prenatal exposure to di(2-ethylhexyl) phthalate impairs development of the mouse neocortex [J]. Toxicology Letters, 2016, 259: 69-79 Smith C A, MacDonald A, Holahan M R. Acute postnatal exposure to di(2-ethylhexyl) phthalate adversely impacts hippocampal development in the male rat [J]. Neuroscience, 2011, 193: 100-108 You M D, Dong J, Fu Y Y, et al. Exposure to di-(2-ethylhexyl) phthalate during perinatal period gender-specifically impairs the dendritic growth of pyramidal neurons in rat offspring [J]. Frontiers in Neuroscience, 2018, 12: 444 Aung K H, Win-Shwe T T, Kanaya M, et al. Involvement of hemeoxygenase-1 in di(2-ethylhexyl) phthalate (DEHP)-induced apoptosis of neuro-2a cells [J]. The Journal of Toxicological Sciences, 2014, 39(2): 217-229 Wójtowicz A K, Sitarz-Głownia A M, Szczęsna M, et al. The action of di-(2-ethylhexyl) phthalate (DEHP) in mouse cerebral cells involves an impairment in aryl hydrocarbon receptor (AhR) signaling [J]. Neurotoxicity Research, 2019, 35(1): 183-195 Wu Y, Li K, Zuo H X, et al. Primary neuronal-astrocytic co-culture platform for neurotoxicity assessment of di-(2-ethylhexyl) phthalate [J]. Journal of Environmental Sciences, 2014, 26(5): 1145-1153 Li N, Papandonatos G D, Calafat A M, et al. Identifying periods of susceptibility to the impact of phthalates on children’s cognitive abilities [J]. Environmental Research, 2019, 172: 604-614 Zhang Q, Chen X Z, Huang X, et al. The association between prenatal exposure to phthalates and cognition and neurobehavior of children-evidence from birth cohorts [J]. Neurotoxicology, 2019, 73: 199-212 Huang H B, Kuo P H, Su P H, et al. Prenatal and childhood exposure to phthalate diesters and neurobehavioral development in a 15-year follow-up birth cohort study [J]. Environmental Research, 2019, 172: 569-577 Xu Y, Agrawal S, Cook T J, et al. Di-(2-ethylhexyl)-phthalate affects lipid profiling in fetal rat brain upon maternal exposure [J]. Archives of Toxicology, 2007, 81(1): 57-62 Howdeshell K L, Wilson V S, Furr J, et al. A mixture of five phthalate esters inhibits fetal testicular testosterone production in the Sprague-Dawley rat in a cumulative, dose-additive manner [J]. Toxicological Sciences: An Official Journal of the Society of Toxicology, 2008, 105(1): 153-165 García-Argüello S F, Lopez-Lorenzo B, Cornelissen B, et al. Development ofICMT-11 for imaging caspase-3/7 activity during therapy-induced apoptosis [J]. Cancers, 2020, 12(8): E2191 Tu W, Li W F, Zhu X G, et al. Di-2-ethylhexyl phthalate (DEHP) induces apoptosis of mouse HT22 hippocampal neuronal cells via oxidative stress [J]. Toxicology and Industrial Health, 2020, 36(11): 844-851 Guida N, Laudati G, Galgani M, et al. Histone deacetylase 4 promotes ubiquitin-dependent proteasomal degradation of Sp3 in SH-SY5Y cells treated with di(2-ethylhexyl)phthalate (DEHP), determining neuronal death [J]. Toxicology and Applied Pharmacology, 2014, 280(1): 190-198 Amara I, Scuto M, Zappalà A, et al. Hericium erinaceus prevents DEHP-induced mitochondrial dysfunction and apoptosis in PC12 cells [J]. International Journal of Molecular Sciences, 2020, 21(6): E2138 Qiu F, Zhou Y B, Deng Y K, et al. Knockdown of TNFAIP1 prevents di-(2-ethylhexyl) phthalate-induced neurotoxicity by activating CREB pathway [J]. Chemosphere, 2020, 241: 125114 胡存丽, 仲来福. 邻苯二甲酸(2-乙基已基)酯遗传毒性研究进展[J]. 大连医科大学学报, 2007, 29(2): 185-190 Hu C L, Zhong L F. Genotoxic effects of di(2-ethylbexyl)phthalate in humans and animails [J]. Journal of Dalian Medical University, 2007, 29(2): 185-190 (in Chinese)
柯翔鸿. 邻苯二甲酸(2-乙基己基)酯对小鼠的氧化损伤和生殖毒性分子机制的研究[D]. 武汉: 华中师范大学, 2008: 11 Ke X H. Study on the oxidative damage and reproductive toxicity molecular mechanism of di-(2-ethylhexyl) phthalate in mice [D]. Wuhan: Central China Normal University, 2008: 11 (in Chinese)
Andries A, Rozenski J, Vermeersch P, et al. Recent progress in the LC-MS/MS analysis of oxidative stress biomarkers [J]. Electrophoresis, 2021, 42(4): 402-428 Rhee S G. Overview on peroxiredoxin [J]. Molecules and Cells, 2016, 39(1): 1-5 Lee D G, Kim K M, Lee H S, et al. Peroxiredoxin 5 prevents diethylhexyl phthalate-induced neuronal cell death by inhibiting mitochondrial fission in mouse hippocampal HT-22 cells [J]. Neurotoxicology, 2019, 74: 242-251 Lu C J, Luo J J, Liu Y, et al. The oxidative stress responses caused by phthalate acid esters increases mRNA abundance of base excision repair (BER) genes in vivo and in vitro [J]. Ecotoxicology and Environmental Safety, 2021, 208: 111525 Luo Y, Li X N, Zhao Y, et al. DEHP triggers cerebral mitochondrial dysfunction and oxidative stress in quail (Coturnix japonica) via modulating mitochondrial dynamics and biogenesis and activating Nrf2-mediated defense response [J]. Chemosphere, 2019, 224: 626-633 Grindler N M, Vanderlinden L, Karthikraj R, et al. Exposure to phthalate, an endocrine disrupting chemical, alters the first trimester placental methylome and transcriptome in women [J]. Scientific Reports, 2018, 8(1): 6086 Saul D, Kosinsky R L. Epigenetics of aging and aging-associated diseases [J]. International Journal of Molecular Sciences, 2021, 22(1): 401 Singh S, Li S S L. Epigenetic effects of environmental chemicals bisphenol A and phthalates [J]. International Journal of Molecular Sciences, 2012, 13(8): 10143-10153 Stappert L, Klaus F, Brüstle O. microRNAs engage in complex circuits regulating adult neurogenesis [J]. Frontiers in Neuroscience, 2018, 12: 707 Luu B E, Green S R, Childers C L, et al. The roles of hippocampal microRNAs in response to acute postnatal exposure to di(2-ethylhexyl) phthalate in female and male rats [J]. Neurotoxicology, 2017, 59: 98-104 Sarangdhar M A, Chaubey D, Srikakulam N, et al. Parentally inherited long non-coding RNA Cyrano is involved in zebrafish neurodevelopment [J]. Nucleic Acids Research, 2018, 46(18): 9726-9735 Latoszek E, Czeredys M. Molecular components of store-operated calcium channels in the regulation of neural stem cell physiology, neurogenesis, and the pathology of Huntington’s disease [J]. Frontiers in Cell and Developmental Biology, 2021, 9: 657337 Kelemen K, Szilágyi T. New approach for untangling the role of uncommon calcium-binding proteins in the central nervous system [J]. Brain Sciences, 2021, 11(5): 634 Tully K, Kupfer D, Dopico A M, et al. A plasticizer released from Ⅳ drip Chambers elevates calcium levels in neurosecretory terminals [J]. Toxicology and Applied Pharmacology, 2000, 168(3): 183-188 Ran D Z, Cai S, Wu H L, et al. Di (2-ethylhexyl) phthalate modulates cholinergic mini-presynaptic transmission of projection neurons in Drosophila antennal lobe [J]. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association, 2012, 50(9): 3291-3297 Feng W W, Liu Y C, Ding Y Y, et al. Typical neurobehavioral methods and transcriptome analysis reveal the neurotoxicity and mechanisms of di(2-ethylhexyl) phthalate on pubertal male ICR mice with type 2 diabetes mellitus [J]. Archives of Toxicology, 2020, 94(4): 1279-1302 Mattson M P, Maudsley S, Martin B. BDNF and 5-HT: A dynamic Duo in age-related neuronal plasticity and neurodegenerative disorders [J]. Trends in Neurosciences, 2004, 27(10): 589-594 Inoue T, Takamatsu Y, Okamura M, et al. Specific inhibition of α5 subunit-containing GABAA receptors enhances locomotor activity and neuronal activity in the motor cortex [J]. Biomedical Research, 2021, 42(3): 103-108 Carbone S, Szwarcfarb B, Ponzo O, et al. Impact of gestational and lactational phthalate exposure on hypothalamic content of amino acid neurotransmitters and FSH secretion in peripubertal male rats [J]. Neurotoxicology, 2010, 31(6): 747-751 Holahan M R, Smith C A, Luu B E, et al. Preadolescent phthalate (DEHP) exposure is associated with elevated locomotor activity and reward-related behavior and a reduced number of tyrosine hydroxylase positive neurons in post-adolescent male and female rats [J]. Toxicological Sciences: An Official Journal of the Society of Toxicology, 2018, 165(2): 512-530 Carbone S, Ponzo O J, Gobetto N, et al. Effect of di(2-ethylhexyl) phthalate on the neuroendocrine regulation of reproduction in adult male rats and its relationship to anxiogenic behavior: Participation of GABAergic system [J]. Human & Experimental Toxicology, 2019, 38(1): 25-35 Li Y N, Fang R Y, Liu Z H, et al. The association between toxic pesticide environmental exposure and Alzheimer’s disease: A scientometric and visualization analysis [J]. Chemosphere, 2021, 263: 128238 Rahman M A, Rahman M S, Uddin M J, et al. Emerging risk of environmental factors: Insight mechanisms of Alzheimer’s diseases [J]. Environmental Science and Pollution Research International, 2020, 27(36): 44659-44672 Mir R H, Sawhney G, Pottoo F H, et al. Role of environmental pollutants in Alzheimer’s disease: A review [J]. Environmental Science and Pollution Research International, 2020, 27(36): 44724-44742 Sun W, Ban J B, Zhang N, et al. Perinatal exposure to di-(2-ethylhexyl)-phthalate leads to cognitive dysfunction and phospho-tau level increase in aged rats [J]. Environmental Toxicology, 2014, 29(5): 596-603 Yen P L, How C M, Hsiu-Chuan Liao V. Early-life and chronic exposure to di(2-ethylhexyl) phthalate enhances amyloid-β toxicity associated with an autophagy-related gene in Caenorhabditis elegans Alzheimer’s disease models [J]. Chemosphere, 2021, 273: 128594 Yu Z, Shi Z H, Zheng Z Y, et al. DEHP induce cholesterol imbalance via disturbing bile acid metabolism by altering the composition of gut microbiota in rats [J]. Chemosphere, 2021, 263: 127959 Yang Y N, Yang Y S H, Lin I H, et al. Phthalate exposure alters gut microbiota composition and IgM vaccine response in human newborns [J]. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association, 2019, 132: 110700 Javed I, Cui X J, Wang X Y, et al. Implications of the human gut-brain and gut-cancer axes for future nanomedicine [J]. ACS Nano, 2020, 14(11): 14391-14416 Needham B D, Kaddurah-Daouk R, Mazmanian S K. Gut microbial molecules in behavioural and neurodegenerative conditions [J]. Nature Reviews Neuroscience, 2020, 21(12): 717-731 Goyal D, Ali S A, Singh R K. Emerging role of gut microbiota in modulation of neuroinflammation and neurodegeneration with emphasis on Alzheimer’s disease [J]. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2021, 106: 110112 -
点击查看大图
计量
- 文章访问数: 4121
- HTML全文浏览数: 4121
- PDF下载数: 216
- 施引文献: 0
下载:
