In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether
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2023
Authors
Radović, BiljanaStojilković, Nikola
Ćurčić, Marijana

Antonijević-Miljaković, Evica

Buha-Đorđević, Aleksandra

Vukelić-Javorac, Dragana

Baralić, Katarina

Đukić-Ćosić, Danijela

Bulat, Zorica

Antonijević, Biljana

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The current study aimed to assess the connection between the mixture of lead (Pb), cadmium (Cd), arsenic (As), methylmercury (MeHg) and decabrominated diphenyl ether (decaBDE) and thyroid function, by using in silico toxicogenomic data-mining approach. To obtain the linkage between investigated toxic mixture and thyroid diseases (TDs), the Comparative Toxicogenomics Database (CTD) was used, while gene ontology (GO) enrichment analysis was performed by ToppGeneSuite portal. The analysis has shown 10 genes connected to all chemicals present in the mixture and TDs (CAT, GSR, IFNG, IL1B, IL4, IL6, MAPK1, SOD2, TGFB1, TNF), most of which were in co-expression (45.68%), or belonged to the same pathway (30.47%). Top 5 biological processes and molecular functions affected by the investigated mixture emphasized the role of two common mechanisms – oxidative stress and inflammation. Cytokines and inflammatory response was listed as the main molecular pathway that may be triggered by simultaneous ...exposure to toxic metal(oid)s and decaBDE and connected to TDs. The direct relations between Pb/decaBDE and redox status impairment in thyroid tissue was confirmed by our chemical-phenotype interaction analysis, while the strongest linkage between Pb, As and decaBDE and thyroid disorders was found. The obtained results provide better understanding of molecular mechanisms involved in the thyrotoxicity of the investigated mixture, and can be used to direct further research.
Keywords:
BDE209 / Co-exposure / Thyroid disruptors / Toxic metal(oid)s / Toxicogenomic data-miningSource:
Toxicology, 2023, 489Publisher:
- Elsevier Ireland Ltd
Funding / projects:
DOI: 10.1016/j.tox.2023.153496
ISSN: 0300-483X
PubMed: 36933645
Scopus: 2-s2.0-85151026514
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PharmacyTY - JOUR AU - Radović, Biljana AU - Stojilković, Nikola AU - Ćurčić, Marijana AU - Antonijević-Miljaković, Evica AU - Buha-Đorđević, Aleksandra AU - Vukelić-Javorac, Dragana AU - Baralić, Katarina AU - Đukić-Ćosić, Danijela AU - Bulat, Zorica AU - Antonijević, Biljana PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4613 AB - The current study aimed to assess the connection between the mixture of lead (Pb), cadmium (Cd), arsenic (As), methylmercury (MeHg) and decabrominated diphenyl ether (decaBDE) and thyroid function, by using in silico toxicogenomic data-mining approach. To obtain the linkage between investigated toxic mixture and thyroid diseases (TDs), the Comparative Toxicogenomics Database (CTD) was used, while gene ontology (GO) enrichment analysis was performed by ToppGeneSuite portal. The analysis has shown 10 genes connected to all chemicals present in the mixture and TDs (CAT, GSR, IFNG, IL1B, IL4, IL6, MAPK1, SOD2, TGFB1, TNF), most of which were in co-expression (45.68%), or belonged to the same pathway (30.47%). Top 5 biological processes and molecular functions affected by the investigated mixture emphasized the role of two common mechanisms – oxidative stress and inflammation. Cytokines and inflammatory response was listed as the main molecular pathway that may be triggered by simultaneous exposure to toxic metal(oid)s and decaBDE and connected to TDs. The direct relations between Pb/decaBDE and redox status impairment in thyroid tissue was confirmed by our chemical-phenotype interaction analysis, while the strongest linkage between Pb, As and decaBDE and thyroid disorders was found. The obtained results provide better understanding of molecular mechanisms involved in the thyrotoxicity of the investigated mixture, and can be used to direct further research. PB - Elsevier Ireland Ltd T2 - Toxicology T1 - In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether VL - 489 DO - 10.1016/j.tox.2023.153496 ER -
@article{ author = "Radović, Biljana and Stojilković, Nikola and Ćurčić, Marijana and Antonijević-Miljaković, Evica and Buha-Đorđević, Aleksandra and Vukelić-Javorac, Dragana and Baralić, Katarina and Đukić-Ćosić, Danijela and Bulat, Zorica and Antonijević, Biljana", year = "2023", abstract = "The current study aimed to assess the connection between the mixture of lead (Pb), cadmium (Cd), arsenic (As), methylmercury (MeHg) and decabrominated diphenyl ether (decaBDE) and thyroid function, by using in silico toxicogenomic data-mining approach. To obtain the linkage between investigated toxic mixture and thyroid diseases (TDs), the Comparative Toxicogenomics Database (CTD) was used, while gene ontology (GO) enrichment analysis was performed by ToppGeneSuite portal. The analysis has shown 10 genes connected to all chemicals present in the mixture and TDs (CAT, GSR, IFNG, IL1B, IL4, IL6, MAPK1, SOD2, TGFB1, TNF), most of which were in co-expression (45.68%), or belonged to the same pathway (30.47%). Top 5 biological processes and molecular functions affected by the investigated mixture emphasized the role of two common mechanisms – oxidative stress and inflammation. Cytokines and inflammatory response was listed as the main molecular pathway that may be triggered by simultaneous exposure to toxic metal(oid)s and decaBDE and connected to TDs. The direct relations between Pb/decaBDE and redox status impairment in thyroid tissue was confirmed by our chemical-phenotype interaction analysis, while the strongest linkage between Pb, As and decaBDE and thyroid disorders was found. The obtained results provide better understanding of molecular mechanisms involved in the thyrotoxicity of the investigated mixture, and can be used to direct further research.", publisher = "Elsevier Ireland Ltd", journal = "Toxicology", title = "In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether", volume = "489", doi = "10.1016/j.tox.2023.153496" }
Radović, B., Stojilković, N., Ćurčić, M., Antonijević-Miljaković, E., Buha-Đorđević, A., Vukelić-Javorac, D., Baralić, K., Đukić-Ćosić, D., Bulat, Z.,& Antonijević, B.. (2023). In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether. in Toxicology Elsevier Ireland Ltd., 489. https://doi.org/10.1016/j.tox.2023.153496
Radović B, Stojilković N, Ćurčić M, Antonijević-Miljaković E, Buha-Đorđević A, Vukelić-Javorac D, Baralić K, Đukić-Ćosić D, Bulat Z, Antonijević B. In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether. in Toxicology. 2023;489. doi:10.1016/j.tox.2023.153496 .
Radović, Biljana, Stojilković, Nikola, Ćurčić, Marijana, Antonijević-Miljaković, Evica, Buha-Đorđević, Aleksandra, Vukelić-Javorac, Dragana, Baralić, Katarina, Đukić-Ćosić, Danijela, Bulat, Zorica, Antonijević, Biljana, "In silico assessment of mixture toxicity mechanisms involved in the pathogenesis of thyroid diseases: The combination of toxic metal(oid)s and decabrominated diphenyl ether" in Toxicology, 489 (2023), https://doi.org/10.1016/j.tox.2023.153496 . .