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Archives of Toxicology

, Volume 91, Issue 4, pp 1859–1870 | Cite as

In vivo cardiomyocyte response to YTX- and AZA-1-induced damage: autophagy versus apoptosis

  • Sara F. Ferreiro
  • Natalia Vilariño
  • Cristina Carrera
  • M. Carmen Louzao
  • Germán Santamarina
  • Antonio G. Cantalapiedra
  • J. Manuel Cifuentes
  • Andrés Crespo
  • Luis M. Botana
Organ Toxicity and Mechanisms

Abstract

Yessotoxins (YTX) and azaspiracids (AZAs) are marine toxins produced by phytoplanktonic dinoflagellates that get accumulated in filter feeding shellfish and finally reach human consumers through the food web. Both toxin classes are worldwide distributed, and food safety authorities have regulated their content in shellfish in many countries. Recently, YTXs and AZAs have been described as compounds with subacute cardiotoxic potential in rats owed to alterations of the cardiovascular function and ultrastructural heart damage. These molecules are also well known in vitro inducers of cell death. The aim of this study was to explore the presence of cardiomyocyte death after repeated subacute exposure of rats to AZA-1 and YTX for 15 days. Because autophagy and apoptosis are often found in dying cardiomyocytes, several autophagic and apoptotic markers were determined by western blot in heart tissues of these rats. The results showed that hearts from YTX-treated rats presented increased levels of the autophagic markers microtubule-associated protein light chain 3-II (LC3-II) and beclin-1, nevertheless AZA-1-treated hearts evidenced increased levels of the apoptosis markers cleaved caspase-3 and -8, cleaved PARP and Fas ligand. Therefore, while YTX-induced damage to the heart triggers autophagic processes, apoptosis activation occurs in the case of AZA-1. For the first time, activation of cell death signals in cardiomyocytes is demonstrated for these toxins with in vivo experiments, which may be related to alterations of the cardiovascular function.

Keywords

Apoptosis Autophagy Azaspiracid Cardiotoxicity Subacute Yessotoxin 

Notes

Acknowledgments

The research leading to these results has received funding from the following FEDER cofunded grants. From CDTI and Technological Funds, supported by Ministerio de Economía y Competitividad, AGL2012-40185-CO2-01, AGL2014-58210-R, and Consellería de Cultura, Educación e Ordenación Universitaria, GRC2013-016. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD. From the European Union’s Seventh Framework Programme managed by REA—Research Executive Agency (FP7/2007-2013) under grant agreement 312184 PHARMASEA.

Supplementary material

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Supplementary material 1 (DOCX 5244 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Sara F. Ferreiro
    • 1
  • Natalia Vilariño
    • 1
  • Cristina Carrera
    • 1
    • 3
  • M. Carmen Louzao
    • 1
  • Germán Santamarina
    • 2
    • 3
  • Antonio G. Cantalapiedra
    • 2
    • 3
  • J. Manuel Cifuentes
    • 4
  • Andrés Crespo
    • 1
  • Luis M. Botana
    • 1
  1. 1.Departamento de Farmacología, Facultad de VeterinariaUniversidade de Santiago de CompostelaLugoSpain
  2. 2.Departamento de Ciencias Clínicas Veterinarias, Facultad de VeterinariaUniversidade de Santiago de CompostelaLugoSpain
  3. 3.Hospital Veterinario Universitario Rof Codina, Facultad de VeterinariaUniversidade de Santiago de CompostelaLugoSpain
  4. 4.Departamento de Anatomía y Producción Animal, Facultad de VeterinariaUniversidade de Santiago de CompostelaLugoSpain

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