System-wide health risk prediction for 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene(MBP), a major active metabolite of environmental pollutant and food contaminant - Bisphenol A.

Autor: Maadurshni GB; Environmental Health and Toxicology Laboratory, Department of Environmental Sciences, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India., Nagarajan M; Environmental Health and Toxicology Laboratory, Department of Environmental Sciences, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India., Priyadharshini S; Integrated Biocomputing Lab, Department of Bioinformatics, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India., Singaravelu U; Integrated Biocomputing Lab, Department of Bioinformatics, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India., Manivannan J; Environmental Health and Toxicology Laboratory, Department of Environmental Sciences, School of Life Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India. Electronic address: drjmaniau@gmail.com.
Jazyk: angličtina
Zdroj: Toxicology [Toxicology] 2023 Feb; Vol. 485, pp. 153414. Date of Electronic Publication: 2022 Dec 29.
DOI: 10.1016/j.tox.2022.153414
Abstrakt: Human exposure to plastic contaminated foods and environmental micro/nano plastic derived chemicals necessitates system-wide health risk assessment. Hence, current study intend to explore the mode of action (MoA) based adverse outcome pathways of 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), the major active metabolite of bisphenol A (BPA). The computational study employed broad range of target prediction, systems biology tools and molecular docking protocols. Further, validation of MBP targets was done using protein-ligand fluorescence quenching assay, endothelial cell culture and chicken embryo vascular angiogenesis models. Interestingly, the current results illustrate that various physiological signaling pathways (MAPK and VEGF related angiogenesis signaling) and disease progression pathways (hypertension, cancer and endocrine disorders) were enriched as potential targets of MBP. Further, docking studies highlights the possible binding mechanism of MBP with important targets including endothelial nitric oxide synthase (eNOS) and serum albumin (BSA). In addition, the validation studies on MBP-BSA interaction (fluorescence quenching), eNOS derived nitric oxide (NOx) generation in endothelial cells and chicken embryo angiogenesis support the system-wide impacts of MBP with highlights on cardiovascular pathogenesis. Thus, the current observation provides novel insights into the system wide impacts of MBP for the futuristic health risk assessment of plastic derived chemicals.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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