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Subacute Cardiovascular Toxicity of the Marine Phycotoxin Azaspiracid-1 in Rats.
- Source :
-
Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2016 May; Vol. 151 (1), pp. 104-14. Date of Electronic Publication: 2016 Feb 10. - Publication Year :
- 2016
-
Abstract
- Azaspiracids (AZAs) are marine toxins produced by Azadinium spinosum that get accumulated in filter feeding shellfish through the food-web. The first intoxication was described in The Netherlands in 1990, and since then several episodes have been reported worldwide. Azaspiracid-1, AZA-2, and AZA-3 presence in shellfish is regulated by food safety authorities of several countries to protect human health. Azaspiracids have been related to widespread organ damage, tumorogenic properties and acute heart rhythm alterations in vivo but the mechanism of action remains unknown. Azaspiracid toxicity kinetics in vivo and in vitro suggests accumulative effects. We studied subacute cardiotoxicity in vivo after repeated exposure to AZA-1 by evaluation of the ECG, arterial blood pressure, plasmatic heart damage biomarkers, and myocardium structure and ultrastructure. Our results showed that four administrations of AZA-1 along 15 days caused functional signs of heart failure and structural heart alterations in rats at doses ranging from 1 to 55 µg/kg. Azaspiracid-1 altered arterial blood pressure, tissue inhibitors of metalloproteinase-1 plasma levels, heart collagen deposition, and ultrastructure of the myocardium. Overall, these data indicate that repeated exposure to low amounts of AZA-1 causes cardiotoxicity, at doses that do not induce signs of other organic system toxicity. Remarkably, human exposure to AZAs considering current regulatory limits of these toxins may be dangerously close to clearly cardiotoxic doses in rats. These findings should be considered when human risk is estimated particularly in high cardiovascular risk subpopulations.<br /> (© The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
Arterial Pressure drug effects
Biomarkers blood
Cardiotoxicity
Collagen metabolism
Dose-Response Relationship, Drug
Female
Heart Failure blood
Heart Failure physiopathology
Heart Rate drug effects
Inflammation Mediators blood
Myocardium metabolism
Myocardium ultrastructure
Rats, Sprague-Dawley
Risk Assessment
Time Factors
Toxicity Tests, Subacute
Heart Failure chemically induced
Marine Toxins toxicity
Spiro Compounds toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0929
- Volume :
- 151
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Toxicological sciences : an official journal of the Society of Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 26865666
- Full Text :
- https://doi.org/10.1093/toxsci/kfw025