Purinergic Receptor Antagonist A438079 Disrupts Benzo[a]pyrene-Mediated IL-1β, CYP1A and CYP1B Transcript Induction Pathway in Zebrafish: Insights into Possible Mechanisms.

Authors

  • Marcelo Campos Department of Chemistry and Environmental Sciences, Universidade Estadual Paulista (IBILCE/UNESP), Rua Cristóvão Colombo, 2265, CEP-15054-000, São José do Rio Preto, São Paulo, Brazil.
  • Claudiana Lameu Departament of Biochemistry, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
  • André Chamelete Department of Chemistry and Environmental Sciences, Universidade Estadual Paulista (IBILCE/UNESP), Rua Cristóvão Colombo, 2265, CEP-15054-000, São José do Rio Preto, São Paulo, Brazil.
  • Alexandre Vidotto Barbosa Lima Department of Chemistry and Environmental Sciences, Universidade Estadual Paulista (IBILCE/UNESP), Rua Cristóvão Colombo, 2265, CEP-15054-000, São José do Rio Preto, São Paulo, Brazil.
  • Natalia Cândido Laboratory of Genomics Studies, (IBILCE/UNESP), São José do Rio Preto, São Paulo, Brazil.
  • Paula Rahal Laboratory of Genomics Studies, (IBILCE/UNESP), São José do Rio Preto, São Paulo, Brazil.
  • Henning Ulrich Departament of Biochemistry, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
  • Eduardo Alves de Almeida Department of Natural Sciences, Fundação Universidade Regional de Blumenau, Blumenau, SC, Brazil.

DOI:

https://doi.org/10.5132/eec.2022.02.09

Keywords:

A438079 benzo[a]pyrene, CYP1A1, CYP1B1, gene transcription, P2X7, zebrafish

Abstract

 The deleterious effects of benzo[a]pyrene are mainly due its metabolites generated by CYP1 metabolism. P2X7 is an important member of purinergic receptors involved in diverse cell signaling cascades, as the inflammasome pathway. Receptor blocking has beneficial effects in several models of inflammatory and neurological diseases. In our study, we show for the first time that the A438079, a “selective” P2X7 antagonist, promotes a down regulation in IL-1β, CYP1A1 and CYP1B1 gene transcription in Danio rerio gills exposed to benzo[a]pyrene. Our results shows a modulation of IL-1β and CYP1 mRNAs, suggesting a possible novel mechanism involving the P2X7 receptor in benzo[a]pyrene-mediated CYP1 induction. Nevertheless, as A438079 was also proven to block the membrane ATP channel pannexin-1, the effects of this compound on downregulating CYPs transcription would be also due to a disruption on Ca2+ influx necessary to activate CYPs transcription by the AhR-Arnt pathway.

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Published

31-01-2023

How to Cite

Campos, M., Lameu, C., Chamelete, A., Vidotto Barbosa Lima, A., Cândido, N., Rahal, P., Ulrich, H., & Alves de Almeida, E. (2023). Purinergic Receptor Antagonist A438079 Disrupts Benzo[a]pyrene-Mediated IL-1β, CYP1A and CYP1B Transcript Induction Pathway in Zebrafish: Insights into Possible Mechanisms. Ecotoxicology and Environmental Contamination, 17(2), 78–84. https://doi.org/10.5132/eec.2022.02.09

Issue

Vol. 17 No. 2 (2022)

Section

Original Articles

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