title: In vivo cardiomyocyte response to YTX- and AZA-1-induced damage: autophagy versus apoptosis.
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.
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain.
authors.forename: Sara F
authors.initials: SF
authors.lastname: Ferreiro
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain. natalia.vilarino@usc.es.
authors.forename: Natalia
authors.initials: N
authors.lastname: Vilariño
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain.|Hospital Veterinario Universitario Rof Codina, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Carrera
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Louzao
authors.affiliation: Departamento de Ciencias Clínicas Veterinarias, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain.|Hospital Veterinario Universitario Rof Codina, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Santamarina
authors.affiliation: Departamento de Ciencias Clínicas Veterinarias, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain.|Hospital Veterinario Universitario Rof Codina, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain.
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Cantalapiedra
authors.affiliation: Departamento de Anatomía y Producción Animal, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain.
authors.forename: J Manuel
authors.initials: JM
authors.lastname: Cifuentes
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Crespo
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidade de Santiago de Compostela, 27002, Lugo, Spain. luis.botana@usc.es.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Botana
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D005260:Female; D008387:Marine Toxins / Q000008:administration & dosage / Q000633:toxicity*; D008978:Mollusk Venoms; D032383:Myocytes, Cardiac / Q000187:drug effects*; D035964:Oxocins / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013141:Spiro Compounds / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D059551:Toxicity Tests, Subacute / Q000379:methods; D000095702:Polyether Toxins
chemical_list: D015415:Biomarkers; D008387:Marine Toxins; D008978:Mollusk Venoms; D035964:Oxocins; D013141:Spiro Compounds; C406592:azaspiracid; D000095702:Polyether Toxins; C066632:yessotoxin
keywords: Apoptosis; Autophagy; Azaspiracid; Cardiotoxicity; Subacute; Yessotoxin