Yessotoxin: cardiotoxicity study in vivo

SF Ferreiro1, N Vilariño1, C Carrera3,1, MC Louzao1, A Cantalapiedra2,3, G Santamarina2,3, LP Rodríguez1, LM Botana1. 1Universidad de Santiago de Compostela Facultad de Veterinaria, Farmacología y Terapéutica, Spain, 2Universidad de Santiago de Compostela Facultad de Veterinaria, Ciencias clínicas veterinarias, Spain, 3Universidad de Santiago de Compostela Facultad de Veterinaria, Hospital Veterinario Universitario Rof Codina, Spain

Yessotoxins (YTXs) are polycyclic ether compounds produced by dinoglagellates that accumulate in filter feeding shellfish. The presence of some marine toxins in seafood is a serious health risk for humans. Yessotoxin levels in shellfish destined for human consumers have been regulated for years by European legislation in order to protect human health. However, the threat that yessotoxin pose to humans is controversial due to the lack of evidence regarding yessotoxin toxicity. Although initially classified as diarrheic toxins, currently they are considered cardiotoxic due to ultraestructural changes observed in cardiomyocytes after oral and intraperitoneal administration. However, no evidence of an effect on heart function has been reported. The aim of this study was to study the acute cardiotoxicity of this group of toxins in vivo. For this purpose, following the recommendations of the guideline S7B of the EMEA, yessotoxin was administered by intravenous injection to anesthetized rats and several parameters of cardiac function were monitored for six hours. The dose of yessotoxin was 10 µg/kg (ten times lower than the intraperitoneal LD50). Heart rate, QT interval, PR interval, morphology of T wave and the occurrence of arrhythmias were evaluated using ECG recordings. Troponin I levels, a biomarker of myocardium injury, were quantified in plasma samples by a specific ELISA kit. None of the ECG measurements changed when the compound was injected or through the whole duration of the experiment. Furthermore there are no evidences of proarrhythmic risk. Finally, troponin I levels in blood did not indicate myocardial injury. Some of the animals (3/7) that were administered with this dose of yessotoxin died before four hours, but none of them showed signs of altered cardiac function before the onset of apnea. This study suggests that these compounds do not induce acute cardiotoxicity, nevertheless more studies both in vivo and in vitro are necessary to evaluate the toxic potential of this group of toxins and the risk they pose to human health.