Ferreiro Sara F, Vilariño Natalia, Carrera Cristina, Louzao M Carmen, Cantalapiedra Antonio G, Santamarina Germán, Cifuentes J Manuel, Vieira Andrés C, Botana Luis M
*Departamento de Farmacología
*Departamento de Farmacología Hospital Veterinario Universitario Rof Codina.
Toxicol Sci. 2016 May;151(1):104-14. doi: 10.1093/toxsci/kfw025. Epub 2016 Feb 10.
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.
azaspiracids（AZAs）是由多棘阿扎藻产生的海洋毒素，通过食物网在滤食性贝类中积累。1990年在荷兰首次描述了中毒事件，此后全球范围内报告了多起此类事件。几个国家的食品安全当局对贝类中azaspiracid-1、AZA-2和AZA-3的存在进行监管，以保护人类健康。azaspiracids与体内广泛的器官损伤、致癌特性和急性心律改变有关，但其作用机制尚不清楚。azaspiracid在体内和体外的毒性动力学表明存在累积效应。我们通过评估心电图、动脉血压、血浆心脏损伤生物标志物以及心肌结构和超微结构，研究了重复暴露于AZA-1后体内的亚急性心脏毒性。我们的结果表明，在15天内四次给予AZA-1，剂量范围为1至55μg/kg时，会导致大鼠出现心力衰竭的功能体征和心脏结构改变。azaspiracid-1改变了动脉血压、金属蛋白酶-1血浆水平的组织抑制剂、心脏胶原沉积以及心肌的超微结构。总体而言，这些数据表明，重复暴露于低剂量的AZA-1会导致心脏毒性，而这些剂量不会诱发其他有机系统毒性的体征。值得注意的是，考虑到这些毒素的当前监管限值，人类接触AZAs的剂量可能危险地接近大鼠明显的心脏毒性剂量。在评估人类风险时，尤其是在高心血管风险亚人群中，应考虑这些发现。
