TY  - JOUR
PY  - 2016//
TI  - Subacute cardiotoxicity of yessotoxin: in vitro and in vivo studies
JO  - Chemical research in toxicology
A1  - Ferreiro, Sara F.
A1  - Vilariño, Natalia
A1  - Carrera, Cristina
A1  - Louzao, M. Carmen
A1  - Cantalapiedra, Antonio G.
A1  - Santamarina, Germán
A1  - Cifuentes, J. Manuel
A1  - Vieira, Andrés C.
A1  - Botana, Luis M.
SP  - 981
EP  - 990
VL  - 29
IS  - 6
N2  - Yessotoxin (YTX) is a marine phycotoxin produced by dinoflagellates and accumulated in filter feeding shellfish. Although no human intoxication episodes have been reported, YTXs content in shellfish is regulated by many food safety authorities due to their worldwide distribution. YTXs have been related to ultrastructural heart damage in vivo, but the functional consequences in the long term have not been evaluated. In this study we explored the accumulative cardiotoxic potential of YTX in vitro and in vivo. Preliminary in vitro evaluation of cardiotoxicity was based on the effect on hERG (human ether-a-go-go related gene) channel trafficking. In vivo experiments were performed in rats that received repeated administrations of YTX followed by recording of electrocardiogram, arterial blood pressure and plasmatic cardiac biomarkers, and analysis of myocardium structure and ultrastructure. Our results showed that an exposure to 100 nM YTX for 12 or 24 hours caused an increase of extracellular surface hERG channels. Furthermore, remarkable bradycardia and hypotension, structural heart alterations and increased plasma levels of tissue inhibitor of metalloproteinases-1 were observed in rats after four intraperitoneal inyections of YTX at doses of 50 or 70 µg/kg that were administered every 4 days along a period of 15 days. Therefore and for the first time, YTX-induced subacute cardiotoxicity is supported by evidence of cardiovascular function alterations related to its repeated administration. Considering international criteria for marine toxin risk estimation and that the regulatory limit for YTX has been recently raised in many countries, YTX cardiotoxicity might pose a health risk to humans and especially to people with previous cardiovascular risk.<p />  <p>Language: en</p>
LA  - en
SN  - 0893-228X
UR  - http://dx.doi.org/10.1021/acs.chemrestox.6b00012
ID  - ref1
ER  -