Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A
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2023
Authors
Baralić, Katarina
Pavić, Aleksandar

Javorac, Dragana

Živančević, Katarina

Božić, Dragica

Radaković, Nataša

Antonijević-Miljaković, Evica

Buha-Đorđević, Aleksandra

Ćurčić, Marijana

Bulat, Zorica

Antonijević, Biljana

Đukić-Ćosić, Danijela

Article (Published version)

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Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP + DBP + BPA. Zebrafish embryos were exposed to the investigated substances in different doses, singularly and combined (binary and ternary mixtures). Liver injury was linked to 75 DEHP, DBP, and BPA genes, mostly connected to inflammation/oxidative stress. In rats, significant alterations in redox status/bioelements and pathohistology were most notable or exclusively present in MIX (probable additive effects). BPA decreased liver area (LA) index in dose-dependent manner. DEHP (<... 2 µg/mL) and DBP (≤ 5 µg/mL) reduced LA values, while their higher doses increased LA index. The effect of DBP in binary mixtures led to a lethal outcome at the two highest concentrations, while the hepatotoxicity of DEHP/DBP/BPA mixture was dictated by BPA (confirmed by the benchmark dose analysis).
Keywords:
Plasticizers / Toxicogenomic data mining / Hepatotoxicity / Rat / ZebrafishSource:
Journal of Hazardous Materials, 2023, 445Publisher:
- Elsevier B.V.
Funding / projects:
DOI: 10.1016/j.jhazmat.2022.130404
ISSN: 0304-3894
PubMed: 36455319
WoS: 000903718900004
Scopus: 2-s2.0-85142897881
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PharmacyTY - JOUR AU - Baralić, Katarina AU - Pavić, Aleksandar AU - Javorac, Dragana AU - Živančević, Katarina AU - Božić, Dragica AU - Radaković, Nataša AU - Antonijević-Miljaković, Evica AU - Buha-Đorđević, Aleksandra AU - Ćurčić, Marijana AU - Bulat, Zorica AU - Antonijević, Biljana AU - Đukić-Ćosić, Danijela PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4334 AB - Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP + DBP + BPA. Zebrafish embryos were exposed to the investigated substances in different doses, singularly and combined (binary and ternary mixtures). Liver injury was linked to 75 DEHP, DBP, and BPA genes, mostly connected to inflammation/oxidative stress. In rats, significant alterations in redox status/bioelements and pathohistology were most notable or exclusively present in MIX (probable additive effects). BPA decreased liver area (LA) index in dose-dependent manner. DEHP (< 2 µg/mL) and DBP (≤ 5 µg/mL) reduced LA values, while their higher doses increased LA index. The effect of DBP in binary mixtures led to a lethal outcome at the two highest concentrations, while the hepatotoxicity of DEHP/DBP/BPA mixture was dictated by BPA (confirmed by the benchmark dose analysis). PB - Elsevier B.V. T2 - Journal of Hazardous Materials T1 - Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A VL - 445 DO - 10.1016/j.jhazmat.2022.130404 ER -
@article{ author = "Baralić, Katarina and Pavić, Aleksandar and Javorac, Dragana and Živančević, Katarina and Božić, Dragica and Radaković, Nataša and Antonijević-Miljaković, Evica and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela", year = "2023", abstract = "Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP + DBP + BPA. Zebrafish embryos were exposed to the investigated substances in different doses, singularly and combined (binary and ternary mixtures). Liver injury was linked to 75 DEHP, DBP, and BPA genes, mostly connected to inflammation/oxidative stress. In rats, significant alterations in redox status/bioelements and pathohistology were most notable or exclusively present in MIX (probable additive effects). BPA decreased liver area (LA) index in dose-dependent manner. DEHP (< 2 µg/mL) and DBP (≤ 5 µg/mL) reduced LA values, while their higher doses increased LA index. The effect of DBP in binary mixtures led to a lethal outcome at the two highest concentrations, while the hepatotoxicity of DEHP/DBP/BPA mixture was dictated by BPA (confirmed by the benchmark dose analysis).", publisher = "Elsevier B.V.", journal = "Journal of Hazardous Materials", title = "Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A", volume = "445", doi = "10.1016/j.jhazmat.2022.130404" }
Baralić, K., Pavić, A., Javorac, D., Živančević, K., Božić, D., Radaković, N., Antonijević-Miljaković, E., Buha-Đorđević, A., Ćurčić, M., Bulat, Z., Antonijević, B.,& Đukić-Ćosić, D.. (2023). Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A. in Journal of Hazardous Materials Elsevier B.V.., 445. https://doi.org/10.1016/j.jhazmat.2022.130404
Baralić K, Pavić A, Javorac D, Živančević K, Božić D, Radaković N, Antonijević-Miljaković E, Buha-Đorđević A, Ćurčić M, Bulat Z, Antonijević B, Đukić-Ćosić D. Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A. in Journal of Hazardous Materials. 2023;445. doi:10.1016/j.jhazmat.2022.130404 .
Baralić, Katarina, Pavić, Aleksandar, Javorac, Dragana, Živančević, Katarina, Božić, Dragica, Radaković, Nataša, Antonijević-Miljaković, Evica, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, "Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A" in Journal of Hazardous Materials, 445 (2023), https://doi.org/10.1016/j.jhazmat.2022.130404 . .