PBTK-TD model of the phagocytosis activity in three-spined stickleback exposed to BPA.

Autor: Mit C; Experimental Toxicology and Modeling Unit, INERIS, UMR-I 02 SEBIO, Verneuil en Halatte 65550, France; Ecotoxicology of Substances and Fields Unit, INERIS, UMR-I 02 SEBIO, Verneuil en Halatte 65550, France., Bado-Nilles A; Ecotoxicology of Substances and Fields Unit, INERIS, UMR-I 02 SEBIO, Verneuil en Halatte 65550, France., Turiès C; Ecotoxicology of Substances and Fields Unit, INERIS, UMR-I 02 SEBIO, Verneuil en Halatte 65550, France., Daniele G; Univ Lyon, CNRS, Université Claude Bernard Lyon 1, Institut des Sciences Analytiques, UMR 5280, 5 rue de la Doua, Villeurbanne F-69100, France., Giroud B; Univ Lyon, CNRS, Université Claude Bernard Lyon 1, Institut des Sciences Analytiques, UMR 5280, 5 rue de la Doua, Villeurbanne F-69100, France., Beaudouin R; Experimental Toxicology and Modeling Unit, INERIS, UMR-I 02 SEBIO, Verneuil en Halatte 65550, France. Electronic address: remy.beaudouin@ineris.fr.
Jazyk: angličtina
Zdroj: Aquatic toxicology (Amsterdam, Netherlands) [Aquat Toxicol] 2023 Aug; Vol. 261, pp. 106608. Date of Electronic Publication: 2023 Jun 10.
DOI: 10.1016/j.aquatox.2023.106608
Abstrakt: Due to the high production volume and persistence in the environment of bisphenol A (BPA) and its substitutes, realistic exposure scenarii were proposed in some species to better understand the relationship between external and internal concentrations. For example, a recent PBTK model has been developed and adapted to BPA ADME (Absorption, Distribution, Metabolization, and Excretion) processes in three-spined stickleback. These substances have an impact on organism physiology including reproductive and immune functions. In this context, physiologically-based toxicokinetic models coupled with toxicodynamics (PBTK-TD) have proven to be valuable tools to fill the knowledge gap between external exposure and effect dynamics. The aim of the current work was to explain the impact of BPA on the immune response by determining its temporality. In addition, the relationship between BPA dose and these responses was investigated using a PBTK-TD model. Two experiments were performed on stickleback to characterize their biomarker responses, (i) a short exposure (14 days) at 0, 10 and 100 µg/L, including a depuration phase (7 days), and (ii) a long exposure (21 days) at 100 µg/L to measure the immunomarker dynamic over a long period. The fish spleens were sampled to analyze immune responses of stickleback at various times of exposure and depuration: leucocyte distribution, phagocytic capacity and efficiency, lysosomal presence and leucocyte respiratory burst index. At the same date, blood, muscle, and liver were sampled to quantify BPA and their metabolites (BPA monoglucuronide and BPA monosulfate). All these data enabled the development of the indirect pharmacodynamic models (PBTK-TD) by implementing the responses of biomarkers in the existing BPA PBTK of stickleback. The results shown a high induction of phagocytosis activity by BPA in the two exposure conditions. Furthermore, the immunomarkers exhibit very different temporal dynamics. This study demonstrates the need of a thorough characterization of biomarker response for a further use in Environmental Biomonitoring.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bado-Nilles Anne reports financial support was provided by French National program EC2CO. Beaudouin R reports financial support was provided by The European Partnership for the Assessment of Risks from Chemicals (Grant Agreement No 101,057,014).
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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