Involvement of toxic metals and PCBs mixture in the thyroid and male reproductive toxicity: In silico toxicogenomic data mining
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2023
Authors
Stojilković, Nikola
Radović, Biljana
Vukelić, Dragana

Ćurčić, Marijana

Antonijević-Miljaković, Evica

Buha-Đorđević, Aleksandra

Baralić, Katarina

Marić, Đurđica

Bulat, Zorica

Đukić-Ćosić, Danijela

Antonijević, Biljana

Article (Published version)

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Toxicological research is mostly limited to considering the effects of a single substance, even though the real exposure of people is reflected in their daily exposure to many different chemical substances in low-doses. This in silico toxicogenomic study aims to provide evidence for the selected environmental (organo)metals (lead, cadmium, methyl mercury) + polychlorinated biphenyls mixture involvement in the possible alteration of thyroid, and male reproductive system function, and furthermore to predict the possible toxic mechanisms of the environmental cocktail. The Comparative Toxicogenomic Database, GeneMANIA online software, and ToppGene Suite portal were used as the main tools for toxicogenomic data mining and gene ontology analysis. The results show that 35 annotated common genes between selected chemicals and endocrine system diseases can interact on the co-expression level. Our study highlighted the disruption of the cytokines, the cell's response to oxidative stress, and the... influence of the transcription factors as the potential core of toxicological mechanisms of the discussed mixture's effects. The connected toxicological effects of the tested mixture were abnormal sperm cells, a disrupted level of testosterone, and thyroid hormones. The core mechanisms of these effects were inflammation, oxidative stress, disruption of androgen receptor signaling, and the alteration of the FOXO3-Keap-1/NRF2-HMOX1-NQO1 pathway signaling most likely controlled by the co-expression of overlapped genes among used chemicals. This in silico research can be used as a potential core for the determination of biomarkers that can be monitored in future further in vitro and in vivo experiments.
Keywords:
Oxidative stress / Inflammation / Bioinformatics / Androgen receptor / Heavy metals / PCBsSource:
Environmental Research, 2023Publisher:
- Elsevier
Funding / projects:
DOI: 10.1016/j.envres.2023.117274
ISSN: 0013-9351
PubMed: 37797666
Scopus: 2-s2.0-85173480663
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PharmacyTY - JOUR AU - Stojilković, Nikola AU - Radović, Biljana AU - Vukelić, Dragana AU - Ćurčić, Marijana AU - Antonijević-Miljaković, Evica AU - Buha-Đorđević, Aleksandra AU - Baralić, Katarina AU - Marić, Đurđica AU - Bulat, Zorica AU - Đukić-Ćosić, Danijela AU - Antonijević, Biljana PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5142 AB - Toxicological research is mostly limited to considering the effects of a single substance, even though the real exposure of people is reflected in their daily exposure to many different chemical substances in low-doses. This in silico toxicogenomic study aims to provide evidence for the selected environmental (organo)metals (lead, cadmium, methyl mercury) + polychlorinated biphenyls mixture involvement in the possible alteration of thyroid, and male reproductive system function, and furthermore to predict the possible toxic mechanisms of the environmental cocktail. The Comparative Toxicogenomic Database, GeneMANIA online software, and ToppGene Suite portal were used as the main tools for toxicogenomic data mining and gene ontology analysis. The results show that 35 annotated common genes between selected chemicals and endocrine system diseases can interact on the co-expression level. Our study highlighted the disruption of the cytokines, the cell's response to oxidative stress, and the influence of the transcription factors as the potential core of toxicological mechanisms of the discussed mixture's effects. The connected toxicological effects of the tested mixture were abnormal sperm cells, a disrupted level of testosterone, and thyroid hormones. The core mechanisms of these effects were inflammation, oxidative stress, disruption of androgen receptor signaling, and the alteration of the FOXO3-Keap-1/NRF2-HMOX1-NQO1 pathway signaling most likely controlled by the co-expression of overlapped genes among used chemicals. This in silico research can be used as a potential core for the determination of biomarkers that can be monitored in future further in vitro and in vivo experiments. PB - Elsevier T2 - Environmental Research T1 - Involvement of toxic metals and PCBs mixture in the thyroid and male reproductive toxicity: In silico toxicogenomic data mining DO - 10.1016/j.envres.2023.117274 ER -
@article{ author = "Stojilković, Nikola and Radović, Biljana and Vukelić, Dragana and Ćurčić, Marijana and Antonijević-Miljaković, Evica and Buha-Đorđević, Aleksandra and Baralić, Katarina and Marić, Đurđica and Bulat, Zorica and Đukić-Ćosić, Danijela and Antonijević, Biljana", year = "2023", abstract = "Toxicological research is mostly limited to considering the effects of a single substance, even though the real exposure of people is reflected in their daily exposure to many different chemical substances in low-doses. This in silico toxicogenomic study aims to provide evidence for the selected environmental (organo)metals (lead, cadmium, methyl mercury) + polychlorinated biphenyls mixture involvement in the possible alteration of thyroid, and male reproductive system function, and furthermore to predict the possible toxic mechanisms of the environmental cocktail. The Comparative Toxicogenomic Database, GeneMANIA online software, and ToppGene Suite portal were used as the main tools for toxicogenomic data mining and gene ontology analysis. The results show that 35 annotated common genes between selected chemicals and endocrine system diseases can interact on the co-expression level. Our study highlighted the disruption of the cytokines, the cell's response to oxidative stress, and the influence of the transcription factors as the potential core of toxicological mechanisms of the discussed mixture's effects. The connected toxicological effects of the tested mixture were abnormal sperm cells, a disrupted level of testosterone, and thyroid hormones. The core mechanisms of these effects were inflammation, oxidative stress, disruption of androgen receptor signaling, and the alteration of the FOXO3-Keap-1/NRF2-HMOX1-NQO1 pathway signaling most likely controlled by the co-expression of overlapped genes among used chemicals. This in silico research can be used as a potential core for the determination of biomarkers that can be monitored in future further in vitro and in vivo experiments.", publisher = "Elsevier", journal = "Environmental Research", title = "Involvement of toxic metals and PCBs mixture in the thyroid and male reproductive toxicity: In silico toxicogenomic data mining", doi = "10.1016/j.envres.2023.117274" }
Stojilković, N., Radović, B., Vukelić, D., Ćurčić, M., Antonijević-Miljaković, E., Buha-Đorđević, A., Baralić, K., Marić, Đ., Bulat, Z., Đukić-Ćosić, D.,& Antonijević, B.. (2023). Involvement of toxic metals and PCBs mixture in the thyroid and male reproductive toxicity: In silico toxicogenomic data mining. in Environmental Research Elsevier.. https://doi.org/10.1016/j.envres.2023.117274
Stojilković N, Radović B, Vukelić D, Ćurčić M, Antonijević-Miljaković E, Buha-Đorđević A, Baralić K, Marić Đ, Bulat Z, Đukić-Ćosić D, Antonijević B. Involvement of toxic metals and PCBs mixture in the thyroid and male reproductive toxicity: In silico toxicogenomic data mining. in Environmental Research. 2023;. doi:10.1016/j.envres.2023.117274 .
Stojilković, Nikola, Radović, Biljana, Vukelić, Dragana, Ćurčić, Marijana, Antonijević-Miljaković, Evica, Buha-Đorđević, Aleksandra, Baralić, Katarina, Marić, Đurđica, Bulat, Zorica, Đukić-Ćosić, Danijela, Antonijević, Biljana, "Involvement of toxic metals and PCBs mixture in the thyroid and male reproductive toxicity: In silico toxicogenomic data mining" in Environmental Research (2023), https://doi.org/10.1016/j.envres.2023.117274 . .