Assessment of Thyroid Endocrine Disruption Effects of Parabens Using In Vivo, In Vitro, and In Silico Approaches
The extensive applications of parabens in foods, drugs, and cosmetics cause inevitable exposure to humans. Revealing the developmental toxicity of parabens is of utmost importance regarding their safety evaluation. In this study, the effects of four commonly used parabens, including methyl paraben (...
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| Veröffentlicht in: | Environmental science & technology 2022-01, Vol.56 (1), p.460-469 |
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| creator | Liang, Jiefeng Yang, Xiaoxi Liu, Qian S Sun, Zhendong Ren, Zhihua Wang, Xiaoyun Zhang, Qing Ren, Xiaomin Liu, Xiuchang Zhou, Qunfang Jiang, Guibin |
| description | The extensive applications of parabens in foods, drugs, and cosmetics cause inevitable exposure to humans. Revealing the developmental toxicity of parabens is of utmost importance regarding their safety evaluation. In this study, the effects of four commonly used parabens, including methyl paraben (20 ∼ 200 μM), ethyl paraben (20 ∼ 100 μM), propyl paraben (5 ∼ 20 μM), and butyl paraben (BuP, 2 ∼ 10 μM), were investigated on the early development of zebrafish embryos and larvae. The underlying mechanisms were explored from the aspect of their disturbance in the thyroid endocrine system using in vivo, in vitro, and in silico assays. Paraben exposure caused deleterious effects on the early development of zebrafish, with BuP displaying the highest toxicity among all, resulting in the exposure concentration-related mortality, decreased hatching rate, reduced body length, lowered heart rate, and the incidence of malformation. Further investigation showed that paraben exposure reduced thyroid hormone levels and disturbed the transcriptional expressions of the target genes in the hypothalamic–pituitary–thyroid axis. Molecular docking analysis combined with in vitro GH3 cell proliferation assay testified that all test parabens exhibited thyroid receptor agonistic activities. The findings confirmed the developmental toxicity of the test parabens and their thyroid endocrine disruption effects, providing substantial evidence on the safety control of paraben-based preservatives. |
| doi_str_mv | 10.1021/acs.est.1c06562 |
| format | Article |
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Revealing the developmental toxicity of parabens is of utmost importance regarding their safety evaluation. In this study, the effects of four commonly used parabens, including methyl paraben (20 ∼ 200 μM), ethyl paraben (20 ∼ 100 μM), propyl paraben (5 ∼ 20 μM), and butyl paraben (BuP, 2 ∼ 10 μM), were investigated on the early development of zebrafish embryos and larvae. The underlying mechanisms were explored from the aspect of their disturbance in the thyroid endocrine system using in vivo, in vitro, and in silico assays. Paraben exposure caused deleterious effects on the early development of zebrafish, with BuP displaying the highest toxicity among all, resulting in the exposure concentration-related mortality, decreased hatching rate, reduced body length, lowered heart rate, and the incidence of malformation. Further investigation showed that paraben exposure reduced thyroid hormone levels and disturbed the transcriptional expressions of the target genes in the hypothalamic–pituitary–thyroid axis. Molecular docking analysis combined with in vitro GH3 cell proliferation assay testified that all test parabens exhibited thyroid receptor agonistic activities. The findings confirmed the developmental toxicity of the test parabens and their thyroid endocrine disruption effects, providing substantial evidence on the safety control of paraben-based preservatives.</description><identifier>ISSN: 0013-936X</identifier><identifier>EISSN: 1520-5851</identifier><identifier>DOI: 10.1021/acs.est.1c06562</identifier><identifier>PMID: 34930008</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Biocompatibility ; Body length ; Cell proliferation ; Cosmetics ; Danio rerio ; Disruption ; Ecotoxicology and Public Health ; Embryos ; Endocrine disruptors ; Endocrine system ; Exposure ; Hatching ; Heart rate ; Hypothalamus ; In vivo methods and tests ; Larvae ; Molecular docking ; Molecular Docking Simulation ; Parabens - analysis ; Pituitary ; Preservatives ; Preservatives, Pharmaceutical - toxicity ; Propyl paraben ; Safety ; Thyroid ; Thyroid gland ; Thyroid Gland - metabolism ; Toxicity ; Toxicity testing ; Transcription ; Zebrafish ; Zebrafish - metabolism</subject><ispartof>Environmental science & technology, 2022-01, Vol.56 (1), p.460-469</ispartof><rights>2021 American Chemical Society</rights><rights>Copyright American Chemical Society Jan 4, 2022</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a361t-b0ac3e45ccfd1765446ce36917d08d11c3cec563fb3cb61a8f1642ded2a391fb3</citedby><cites>FETCH-LOGICAL-a361t-b0ac3e45ccfd1765446ce36917d08d11c3cec563fb3cb61a8f1642ded2a391fb3</cites><orcidid>0000-0003-2521-100X ; 0000-0002-6335-3917 ; 0000-0003-4759-5016</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.est.1c06562$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.est.1c06562$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34930008$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liang, Jiefeng</creatorcontrib><creatorcontrib>Yang, Xiaoxi</creatorcontrib><creatorcontrib>Liu, Qian S</creatorcontrib><creatorcontrib>Sun, Zhendong</creatorcontrib><creatorcontrib>Ren, Zhihua</creatorcontrib><creatorcontrib>Wang, Xiaoyun</creatorcontrib><creatorcontrib>Zhang, Qing</creatorcontrib><creatorcontrib>Ren, Xiaomin</creatorcontrib><creatorcontrib>Liu, Xiuchang</creatorcontrib><creatorcontrib>Zhou, Qunfang</creatorcontrib><creatorcontrib>Jiang, Guibin</creatorcontrib><title>Assessment of Thyroid Endocrine Disruption Effects of Parabens Using In Vivo, In Vitro, and In Silico Approaches</title><title>Environmental science & technology</title><addtitle>Environ. Sci. Technol</addtitle><description>The extensive applications of parabens in foods, drugs, and cosmetics cause inevitable exposure to humans. Revealing the developmental toxicity of parabens is of utmost importance regarding their safety evaluation. In this study, the effects of four commonly used parabens, including methyl paraben (20 ∼ 200 μM), ethyl paraben (20 ∼ 100 μM), propyl paraben (5 ∼ 20 μM), and butyl paraben (BuP, 2 ∼ 10 μM), were investigated on the early development of zebrafish embryos and larvae. The underlying mechanisms were explored from the aspect of their disturbance in the thyroid endocrine system using in vivo, in vitro, and in silico assays. Paraben exposure caused deleterious effects on the early development of zebrafish, with BuP displaying the highest toxicity among all, resulting in the exposure concentration-related mortality, decreased hatching rate, reduced body length, lowered heart rate, and the incidence of malformation. Further investigation showed that paraben exposure reduced thyroid hormone levels and disturbed the transcriptional expressions of the target genes in the hypothalamic–pituitary–thyroid axis. Molecular docking analysis combined with in vitro GH3 cell proliferation assay testified that all test parabens exhibited thyroid receptor agonistic activities. 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Sci. Technol</addtitle><date>2022-01-04</date><risdate>2022</risdate><volume>56</volume><issue>1</issue><spage>460</spage><epage>469</epage><pages>460-469</pages><issn>0013-936X</issn><eissn>1520-5851</eissn><abstract>The extensive applications of parabens in foods, drugs, and cosmetics cause inevitable exposure to humans. Revealing the developmental toxicity of parabens is of utmost importance regarding their safety evaluation. In this study, the effects of four commonly used parabens, including methyl paraben (20 ∼ 200 μM), ethyl paraben (20 ∼ 100 μM), propyl paraben (5 ∼ 20 μM), and butyl paraben (BuP, 2 ∼ 10 μM), were investigated on the early development of zebrafish embryos and larvae. The underlying mechanisms were explored from the aspect of their disturbance in the thyroid endocrine system using in vivo, in vitro, and in silico assays. Paraben exposure caused deleterious effects on the early development of zebrafish, with BuP displaying the highest toxicity among all, resulting in the exposure concentration-related mortality, decreased hatching rate, reduced body length, lowered heart rate, and the incidence of malformation. Further investigation showed that paraben exposure reduced thyroid hormone levels and disturbed the transcriptional expressions of the target genes in the hypothalamic–pituitary–thyroid axis. Molecular docking analysis combined with in vitro GH3 cell proliferation assay testified that all test parabens exhibited thyroid receptor agonistic activities. The findings confirmed the developmental toxicity of the test parabens and their thyroid endocrine disruption effects, providing substantial evidence on the safety control of paraben-based preservatives.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>34930008</pmid><doi>10.1021/acs.est.1c06562</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-2521-100X</orcidid><orcidid>https://orcid.org/0000-0002-6335-3917</orcidid><orcidid>https://orcid.org/0000-0003-4759-5016</orcidid></addata></record> |
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| subjects | Animals Biocompatibility Body length Cell proliferation Cosmetics Danio rerio Disruption Ecotoxicology and Public Health Embryos Endocrine disruptors Endocrine system Exposure Hatching Heart rate Hypothalamus In vivo methods and tests Larvae Molecular docking Molecular Docking Simulation Parabens - analysis Pituitary Preservatives Preservatives, Pharmaceutical - toxicity Propyl paraben Safety Thyroid Thyroid gland Thyroid Gland - metabolism Toxicity Toxicity testing Transcription Zebrafish Zebrafish - metabolism |
| title | Assessment of Thyroid Endocrine Disruption Effects of Parabens Using In Vivo, In Vitro, and In Silico Approaches |
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