Purinergic Receptor Antagonist A438079 Disrupts Benzo[a]pyrene-Mediated IL-1β, CYP1A and CYP1B Transcript Induction Pathway in Zebrafish: Insights into Possible Mechanisms.
DOI:
https://doi.org/10.5132/eec.2022.02.09Palabras clave:
A438079 benzo[a]pyrene, CYP1A1, CYP1B1, gene transcription, P2X7, zebrafishResumen
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.
Descargas
Descargas
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2022 Ecotoxicology and Environmental Contamination
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
Copyright © 2006 ECOTOX-Brasil
Copyright notice: It is a condition for publication that manuscripts submitted to this journal have not yet been published and will not be simultaneously submitted or published elsewhere. By submitting a manuscript, the authors agree that copyright for their article is transferred to the Sociedade Brasileira de Ecotoxicologia (ECOTOX-Brasil) if and when the article is accepted for publication. The copyright covers the exclusive rights to reproduce and distribute articles, including reprints, photographic reproductions or any other reproduction of a similar nature, including translations. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without permission of the publisher.
Notice: While every effort is made by the EEC, editors and editorial board to see that no inaccurate or misleading data, opinions or statements appear in this journal, they wish to make it clear that the contents of the articles and advertisements published herein are the sole responsibility of the contributors or advertisers concerned. Accordingly, the EEC, the editorial board and editors and their respective employees, officers and agents accept no responsibility or liability whatsoever for the consequences of any inaccurate or misleading data, opinion or statement.
