王力军1,
谢嘉2,
洪美玲1,
丁利1,
李二超2,
刁晓平1,,
1. 海南师范大学热带岛屿生态学教育部重点实验室, 海口 571158;
2. 海南大学海洋学院, 海口 570228
作者简介: 张纪亮(1980-),男,博士,研究方向为生态毒理学,E-mail:jlzhang@hainnu.edu.cn.
通讯作者: 刁晓平,diaoxip@hainu.edu.cn
基金项目: 国家自然科学基金资助项目（U1304329）；海南省高等学校科学研究资助项目（Hnky2020ZD-13）中图分类号: X171.5
Searching for Toxic Pathways of Parabens Using the Comparative Toxicogenomics Database
Zhang Jiliang1,Wang Lijun1,
Xie Jia2,
Hong Meiling1,
Ding Li1,
Li Erchao2,
Diao Xiaoping1,,
1. Ministry of Education Key Laboratory for Ecology of Tropical Islands, Hainan Normal University, Haikou 571158, China;
2. College of Oceanology, Hainan University, Haikou 570228, China
Corresponding author: Diao Xiaoping,diaoxip@hainu.edu.cn
CLC number: X171.5
-->
摘要
HTML全文
图
参考文献
相关文章
施引文献
资源附件
访问统计
摘要:尼泊金酯被广泛用于化妆品、食品以及药物保存的防腐剂，其对生态和人类健康的影响备受关注。目前，比较毒理基因组学数据库已发展成为重要的毒理信息学资源。因此，本研究应用该数据库，通过手动策划，分析了5种常见尼泊金酯影响的潜在基因和通路。结果表明，尼泊金酯共同影响基因主要是雌激素受体以及与脂代谢相关基因；核受体机制，特别是对雌激素受体的干扰作用可能是所有尼泊金酯重要的毒性机制。通过对相关基因分析，尼泊金酯类除了通过性激素受体介导生殖毒性外，还可能影响激素的合成与转运；尼泊金酯类对脂代谢的影响主要表现为对脂肪分化与脂肪因子分泌相关基因的影响。KEGG通路富集分析中，发现大量与生殖相关通路，主要包括两大类：一类与生殖相关激素的合成、分泌及活性有关；另一类则主要与卵巢发育有关。另外，还发现了大量与神经突触信号传递、突触导向、突触可塑性以及神经网络形成等相关的通路，主要与尼泊金丁酯和尼泊金丙酯有关。尽管在尼泊金酯的生殖毒性方面已经开展了大量研究，但尼泊金酯对神经-行为学影响的数据资料还较少，特别是动物实验数据，亟需在该方面开展大量研究，进而对尼泊金酯进行更加全面的生态和健康风险评估。
关键词: 尼泊金酯/
比较毒理基因组学数据库/
综合毒性/
毒性机制
Abstract:Parabens are widely used as preservatives in cosmetics, food or drugs, and thus their impact on ecology or human health has attracted great concern. Comparative Toxicogenomics Database (CTD) has been becoming an important resource for research of toxicological informatics. This study analyzed genes and pathways associated with five commonly used parabens by manual curation using CTD. It is found that the five parabens co-affected genes mainly included estrogen receptors or genes involved in lipid metabolism. The nuclear receptor mechanism, especially for estrogen receptors, might be an important toxicological mechanism for all parabens. By analyzing related genes, in addition to sex hormone receptors, synthesis and transport of sex hormones might be also involved in the reproductive toxicity caused by exposure to parabens. The effects of parabens on lipid metabolism are mainly related to genes for adipocyte differentiation or adipokines. A large number of reproduction related pathways are found, mainly including two categories. One is related to the synthesis, secretion and activity of reproduction related hormones, and the other is mainly related to ovarian development. A large number of pathways related to synaptic signaling, targeting and plasticity, or neural network formation have been found, mainly affected by butylparaben or propylparaben. Despite of the increasing research on reproductive toxicity of parabens, few data of neuro-behavioral effects of parabens, especially animal experimental data, are available. Thus, further research on neurotoxicology is urgently needed for more comprehensively ecological and health risk assessment.
Key words:paraben/
Comparative Toxicogenomics Database/
integrated toxicity/
toxicity mechanism.
| Davis A P, Wiegers T C, Wiegers J, et al. Chemical-induced phenotypes at CTD help inform the predisease state and construct adverse outcome pathways[J]. Toxicological Sciences, 2018, 165(1):145-156 |
| Błędzka D, Gromadzińska J, Wa,sowicz W. Parabens. From environmental studies to human health[J]. Environment International, 2014, 67:27-42 |
| Andersen F A. Final amended report on the safety assessment of methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben, and benzyl-paraben as used in cosmetic products[J]. International Journal of Toxicology, 2009, 27(S4):1-82 |
| Liao C Y, Kannan K. Temporal trends of parabens and their metabolites in mollusks from the Chinese Bohai Sea during 2006-2015:Species-specific accumulation and implications for human exposure[J]. Environmental Science and Technology, 2018, 52(16):9045-9055 |
| Liao C Y, Chen L X, Kannan K. Occurrence of parabens in foodstuffs from China and its implications for human dietary exposure[J]. Environment International, 2013, 57-58:68-74 |
| Calafat A M, Ye X, Wong L Y, et al. Urinary concentrations of four parabens in the U.S. Population:NHANES 2005-2006[J]. Environmental Health Perspectives, 2010, 118(5):679-685 |
| Schlumpf M, Kypke K, Wittassek M, et al. Exposure patterns of UV filters, fragrances, parabens, phthalates, organochlor pesticides, PBDEs, and PCBs in human milk:Correlation of UV filters with use of cosmetics[J]. Chemosphere, 2010, 81(10):1171-1183 |
| Wang L, Asimakopoulos A G, Kannan K. Accumulation of 19 environmental phenolic and xenobiotic heterocyclic aromatic compounds in human adipose tissue[J]. Environment International, 2015, 78:45-50 |
| Czarczyńska-Goślińska B, Zgoła-Grześkowiak A, Jeszka-Skowron M, et al. Detection of bisphenol A, cumylphenol and parabens in surface waters of Greater Poland Voivodeship[J]. Journal of Environmental Management, 2017, 204(1):50-60 |
| Feng J L, Zhao J H, Xi N N, et al. Parabens and their metabolite in surface water and sediment from the Yellow River and the Huai River in Henan Province:Spatial distribution, seasonal variation and risk assessment[J]. Ecotoxicology and Environmental Safety, 2019, 172:480-487 |
| Li H X, Xiao L, Wang C, et al. Review:Epigenetic regulation of adipocyte differentiation and adipogenesis[J]. Journal of Zhejiang University (Science B), 2010, 11(10):784-791 |
| Münzberg H, Morrison C D. Structure, production and signaling of leptin[J]. Metabolism, 2015, 64(1):13-23 |
| Diamanti-Kandarakis E, Bourguignon J P, Giudice L C, et al. Endocrine-disrupting chemicals:An endocrine society scientific statement[J]. Endocrine Reviews, 2009, 30(4):293-342 |
| Watanabe Y, Kojima H, Takeuchi S, et al. Comparative study on transcriptional activity of 17 parabens mediated by estrogen receptor α and β and androgen receptor[J]. Food and Chemical Toxicology, 2013, 57:227-234 |
| Routledge E J, Parker J, Odum J, et al. Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic[J]. Toxicology and Applied Pharmacology, 1998, 153(1):12-19 |
| Ma D H, Chen L J, Zhu X B, et al. Assessment of combined antiandrogenic effects of binary parabens mixtures in a yeast-based reporter assay[J]. Environmental Science and Pollution Research, 2014, 21(10):6482-6494 |
| Verderame M, Scudiero R. Estrogen-dependent, extrahepatic synthesis of vitellogenin in male vertebrates:A mini-review[J]. Comptes Rendus Biologies, 2017, 340(3):139-144 |
| Li Y, Zhang M C, Xu X K, et al. Functional diversity of p53 in human and wild animals[J]. Frontiers in Endocrinology, 2019, 10:152 |
| Darbre P D, Aljarrah A, Miller W R, et al. Concentrations of parabens in human breast tumours[J]. Journal of Applied Toxicology, 2010, 24(1):5-13 |
| Charles A K, Darbre P D. Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF-7 human breast cancer cells[J]. Journal of Applied Toxicology, 2013, 33(5):390-398 |
| Yang X Y, Shen H, Buckley B, et al. NTRK1 is a positive regulator of YAP oncogenic function[J]. Oncogene, 2019, 38(15):2778-2787 |
| Boberg J, Taxvig C, Christiansen S, et al. Possible endocrine disrupting effects of parabens and their metabolites[J]. Reproductive Toxicology, 2010, 30(2):301-312 |
| 刘帅, 胡磊, 杨明. G蛋白偶联雌激素受体1介导的环境雌激素效应研究进展[J]. 生态毒理学报, 2016, 11(1):52-60Liu S, Hu L, Yang M. Research progress of the effects of environmental estrogens mediated by G protein-coupled estrogen receptor 1[J]. Asian Journal of Ecotoxicology, 2016, 11(1):52-60(in Chinese) |
| Blakemore J, Naftolin F. Aromatase:Contributions tophysiology and disease in women and men[J]. Physiology, 2016, 31(4):258-269 |
| Goldštajn M Š, Toljan K, Grgić F, et al. Sex hormone binding globulin (SHBG) as a marker of clinical disorders[J]. Collegium Antropologicum, 2016, 40(3):211-218 |
| 张丹, 梁小弟, 努尔比耶·努尔麦麦提, 等. RNA结合蛋白人抗原R在人脂肪细胞分化中的作用[J]. 中华内分泌代谢杂志, 2017(10):854-860 Zhang D, Liang X D, Nuermaimaiti N, et al. Role of RNA-binding protein HuR in human adipocyte differentiation[J]. Chinese Journal of Endocrinology and Metabolism, 2017(10):854-860(in Chinese) |
| Kumar V, Kumaresan A, Nag P, et al. Transcriptional abundance of type-1 endocannabinoid receptor (CB1) and fatty acid amide hydrolase (FAAH) in bull spermatozoa:Relationship with field fertility[J]. Theriogenology, 2018, 114:252-257 |
| Silvestri C, Di Marzo V. The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders[J]. Cell Metabolism, 2013, 17(4):475-490 |
| Bouaboula M, Hilairet S, Marchand J, et al. Anandamide induced PPARgamma transcriptional activation and 3T3-L1 preadipocyte differentiation[J]. European Journal of Pharmacology, 2005, 517(3):174-181 |
| Karaliota S, Siafaka-Kapadai A, Gontinou C, et al. Anandamide increases the differentiation of rat adipocytes and causes PPAR and CB1 receptor upregulation[J]. Obesity, 2009, 17(10):1830-1838 |
| Kroll C, Mastroeni S S B S, Veugelers P J, et al. Associations of ADIPOQ and LEP gene variants with energy intake:A systematic review[J]. Nutrients, 2019, 11(4):750 |
| Jiang Y, Zhao H, Xia W, et al. Prenatal exposure to benzophenones, parabens and triclosan and neurocognitive development at 2 years[J]. Environment International, 2019, 126:413-421 |
| Luzeena Raja G, Divya Subhashree K, Lite C, et al. Transient exposure of methylparaben to zebrafish (Danio rerio) embryos altered cortisol level, acetylcholinesterase activity and induced anxiety-like behavior[J]. General and Comparative Endocrinology, 2019, 279:53-59 |
| Ali E H, Elgoly A H. Combined prenatal and postnatal butyl paraben exposure produces autism-like symptoms in offspring:Comparison with valproic acid autistic model[J]. Pharmacology Biochemistry and Behavior, 2013, 111:102-110 |
| Guerra M T, Sanabria M, Cagliarani S V, et al. Long-term effects of in utero and lactational exposure to butyl paraben in female rats[J]. Environmental Toxicology, 2017, 32(3):776-788 |
| Valle-Sistac J, Molins-Delgado D, Díaz M, et al. Determination of parabens and benzophenone-type UV filters in human placenta. First description of the existence of benzyl paraben and benzophenone-4[J]. Environment International, 2016, 88:243-249 |
| Glencross B D, De Santis C, Bicskei B, et al. A comparative analysis of the response of the hepatic transcriptome to dietary docosahexaenoic acid in Atlantic salmon(Salmo salar) post-smolts[J]. BMC Genomics, 2015, 16(1):684 |
| Vincentis S D, Monzani M L, Brigante G. Crosstalk between gonadotropins and thyroid axis[J]. Minerva Ginecologica, 2018, 70(5):609-620 |
| Bakos J, Srancikova A, Havranek T, et al. Molecular mechanisms of oxytocin signaling at the synaptic connection[J]. Neural Plasticity, 2018, 2018:4864107 |
| Xiang X, Yu Y, Tang X, et al. Transcriptome profile in hippocampus during acute inflammatory response to surgery:Toward early stage of PND[J]. Frontiers in Immunology, 2019, 10:149 |
| Hashimotodani Y, Ohno-Shosaku T, Kano M. Presynaptic monoacylglycerol lipase activity determines basal endocannabinoid tone and terminates retrograde endocannabinoid signaling in the hippocampus[J]. Journal of Neuroscience, 2007, 27(5):1211-1219 |
| 胡莺燕, 方贻儒. 双相障碍与脑源性神经营养因子信号通路研究进展[J]. 上海交通大学学报:医学版, 2011, 31(11):1546-1549Hu Y Y, Fang Y R. Research progress of bipolar disorder and signaling pathway of brain derived neurotrophic factor[J]. Journal of Shanghai Jiaotong University:Medical Science, 2011, 31(11):1546-1549(in Chinese) |
| 崔光成, 司雨, 李平, 等. 轴突导向通路单核苷酸多态性与精神分裂症易感关联研究[J]. 中华行为医学与脑科学杂志, 2017, 26(12):1096-1100Cui G C, Si Y, Li P, et al. The association between axon guidance pathway single nucleotide polymorphisms and susceptibility to schizophrenia[J]. Chinese Journal of Behavioral Medicine and Brain Science, 2017, 26(12):1096-1100(in Chinese) |
| Berer K, Gerdes L A, Cekanaviciute E, et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice[J]. Proceedings of the National Academy of Sciences, USA, 2017, 114:10719-10724 |
