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 / Zebrafish
TY - 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 . .
