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dc.creatorBaralić, Katarina
dc.creatorPavić, Aleksandar
dc.creatorJavorac, Dragana
dc.creatorŽivančević, Katarina
dc.creatorBožić, Dragica
dc.creatorRadaković, Nataša
dc.creatorAntonijević-Miljaković, Evica
dc.creatorBuha-Đorđević, Aleksandra
dc.creatorĆurčić, Marijana
dc.creatorBulat, Zorica
dc.creatorAntonijević, Biljana
dc.creatorĐukić-Ćosić, Danijela
dc.date.accessioned2022-12-13T09:05:59Z
dc.date.available2022-12-13T09:05:59Z
dc.date.issued2023
dc.identifier.issn0304-3894
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/4334
dc.description.abstractConnections 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).
dc.publisherElsevier B.V.
dc.relationinfo:eu-repo/grantAgreement/MESTD/inst-2020/200161/RS//
dc.rightsrestrictedAccess
dc.sourceJournal of Hazardous Materials
dc.subjectPlasticizers
dc.subjectToxicogenomic data mining
dc.subjectHepatotoxicity
dc.subjectRat
dc.subjectZebrafish
dc.titleComprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A
dc.typearticle
dc.rights.licenseARR
dc.citation.volume445
dc.citation.rankaM21~
dc.identifier.wos000903718900004
dc.identifier.doi10.1016/j.jhazmat.2022.130404
dc.identifier.pmid36455319
dc.identifier.scopus2-s2.0-85142897881
dc.type.versionpublishedVersion


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