Insights into toxicity of polychlorinated naphthalenes to multiple human endocrine receptors: Mechanism and health risk analysis
This study explored the combined disruption mechanism of polychlorinated naphthalenes (PCNs) on the three key receptors (estrogen receptor, thyroid receptor, and adrenoceptor) of the human endocrine system. The intensity of PCN endocrine disruption on these receptors was first determined using a mol...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412022002185 |
| _version_ | 1811245852036956160 |
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| author | Xixi Li Wenwen Gu Baiyu Zhang Xiaying Xin Qiao Kang Min Yang Bing Chen Yu Li |
| author_facet | Xixi Li Wenwen Gu Baiyu Zhang Xiaying Xin Qiao Kang Min Yang Bing Chen Yu Li |
| author_sort | Xixi Li |
| collection | DOAJ |
| description | This study explored the combined disruption mechanism of polychlorinated naphthalenes (PCNs) on the three key receptors (estrogen receptor, thyroid receptor, and adrenoceptor) of the human endocrine system. The intensity of PCN endocrine disruption on these receptors was first determined using a molecular docking method. A comprehensive index of PCN endocrine disruption to human was quantified by analytic hierarchy process and fuzzy analysis. The mode of action between PCNs and the receptors was further identified to screen the molecular characteristics influencing PCN endocrine disruption through molecular docking and fractional factorial design. Quantitative structure–activity relationship (QSAR) models were established to investigate the toxic mechanism due to PCN endocrine disruption. The results showed that the lowest occupied orbital energy (ELUMO) was the most important factor contributing to the toxicity of PCNs on the endocrine receptors, followed by the orbital energy difference (ΔE) and positive Millikan charge (q+). Furthermore, the strategies were formulated through adjusting the nutritious diet to reduce health risk for the workers in PCN contaminated sites and the effectiveness and feasibility were assessed by molecular dynamic simulation. The simulation results indicated that the human health risk caused by PCN endocrine disruption could be effectively decreased by nutritional supplementation. The binding ability between PCNs and endocrine receptors significantly declined (up to −16.45%) with the supplementation of vitamins (A, B2, B12, C, and E) and carotene. This study provided the new insights to reveal the toxic mechanism of PCNs on human endocrine systems and the recommendations on nutritional supplements for health risk reduction. The methodology and findings could serve as valuable references for screening of potential endocrine disruptors and developing appropriate strategies for PCN or other persistent organic pollution control and health risk management. |
| first_indexed | 2024-04-12T14:45:32Z |
| format | Article |
| id | doaj.art-ae23be663b2945529eff511a75344e11 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-12T14:45:32Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-ae23be663b2945529eff511a75344e112022-12-22T03:28:40ZengElsevierEnvironment International0160-41202022-07-01165107291Insights into toxicity of polychlorinated naphthalenes to multiple human endocrine receptors: Mechanism and health risk analysisXixi Li0Wenwen Gu1Baiyu Zhang2Xiaying Xin3Qiao Kang4Min Yang5Bing Chen6Yu Li7Northern Region Persistent Organic Pollution Control (NRPOP) Laboratory, Faculty of Engineering and Applied Science, Memorial University, St. John’s, NL A1B 3X5, CanadaNorthern Region Persistent Organic Pollution Control (NRPOP) Laboratory, Faculty of Engineering and Applied Science, Memorial University, St. John’s, NL A1B 3X5, Canada; MOE Key Laboratory of Resources and Environmental Systems Optimization, North China Electric Power University, Beijing 102206, ChinaNorthern Region Persistent Organic Pollution Control (NRPOP) Laboratory, Faculty of Engineering and Applied Science, Memorial University, St. John’s, NL A1B 3X5, CanadaNorthern Region Persistent Organic Pollution Control (NRPOP) Laboratory, Faculty of Engineering and Applied Science, Memorial University, St. John’s, NL A1B 3X5, CanadaNorthern Region Persistent Organic Pollution Control (NRPOP) Laboratory, Faculty of Engineering and Applied Science, Memorial University, St. John’s, NL A1B 3X5, CanadaNorthern Region Persistent Organic Pollution Control (NRPOP) Laboratory, Faculty of Engineering and Applied Science, Memorial University, St. John’s, NL A1B 3X5, CanadaNorthern Region Persistent Organic Pollution Control (NRPOP) Laboratory, Faculty of Engineering and Applied Science, Memorial University, St. John’s, NL A1B 3X5, Canada; Corresponding authors.MOE Key Laboratory of Resources and Environmental Systems Optimization, North China Electric Power University, Beijing 102206, China; Corresponding authors.This study explored the combined disruption mechanism of polychlorinated naphthalenes (PCNs) on the three key receptors (estrogen receptor, thyroid receptor, and adrenoceptor) of the human endocrine system. The intensity of PCN endocrine disruption on these receptors was first determined using a molecular docking method. A comprehensive index of PCN endocrine disruption to human was quantified by analytic hierarchy process and fuzzy analysis. The mode of action between PCNs and the receptors was further identified to screen the molecular characteristics influencing PCN endocrine disruption through molecular docking and fractional factorial design. Quantitative structure–activity relationship (QSAR) models were established to investigate the toxic mechanism due to PCN endocrine disruption. The results showed that the lowest occupied orbital energy (ELUMO) was the most important factor contributing to the toxicity of PCNs on the endocrine receptors, followed by the orbital energy difference (ΔE) and positive Millikan charge (q+). Furthermore, the strategies were formulated through adjusting the nutritious diet to reduce health risk for the workers in PCN contaminated sites and the effectiveness and feasibility were assessed by molecular dynamic simulation. The simulation results indicated that the human health risk caused by PCN endocrine disruption could be effectively decreased by nutritional supplementation. The binding ability between PCNs and endocrine receptors significantly declined (up to −16.45%) with the supplementation of vitamins (A, B2, B12, C, and E) and carotene. This study provided the new insights to reveal the toxic mechanism of PCNs on human endocrine systems and the recommendations on nutritional supplements for health risk reduction. The methodology and findings could serve as valuable references for screening of potential endocrine disruptors and developing appropriate strategies for PCN or other persistent organic pollution control and health risk management.http://www.sciencedirect.com/science/article/pii/S0160412022002185Polychlorinated naphthalenes (PCNs)Endocrine disruptionHuman health riskQSAR modelMD simulation |
| spellingShingle | Xixi Li Wenwen Gu Baiyu Zhang Xiaying Xin Qiao Kang Min Yang Bing Chen Yu Li Insights into toxicity of polychlorinated naphthalenes to multiple human endocrine receptors: Mechanism and health risk analysis Environment International Polychlorinated naphthalenes (PCNs) Endocrine disruption Human health risk QSAR model MD simulation |
| title | Insights into toxicity of polychlorinated naphthalenes to multiple human endocrine receptors: Mechanism and health risk analysis |
| title_full | Insights into toxicity of polychlorinated naphthalenes to multiple human endocrine receptors: Mechanism and health risk analysis |
| title_fullStr | Insights into toxicity of polychlorinated naphthalenes to multiple human endocrine receptors: Mechanism and health risk analysis |
| title_full_unstemmed | Insights into toxicity of polychlorinated naphthalenes to multiple human endocrine receptors: Mechanism and health risk analysis |
| title_short | Insights into toxicity of polychlorinated naphthalenes to multiple human endocrine receptors: Mechanism and health risk analysis |
| title_sort | insights into toxicity of polychlorinated naphthalenes to multiple human endocrine receptors mechanism and health risk analysis |
| topic | Polychlorinated naphthalenes (PCNs) Endocrine disruption Human health risk QSAR model MD simulation |
| url | http://www.sciencedirect.com/science/article/pii/S0160412022002185 |
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