In vitro and in vivo toxicity study of compounds of natural origin: marine biotoxins

Abstract

This doctoral thesis provides data on different phases necessary for a complete risk assessment of the most common marine biotoxins in Galicia: okadaic acid (OA), their derivatives the dinophysistoxins (DTXs), the azaspiracids (AZAs), and also the emerging toxin: tetrodotoxin (TTX). For this, elimination of the toxic source from the natural environment, the passage of toxins through the gastrointestinal tract, toxic effects, and oral toxicity studies are evaluated. Natural clays with smaller particle size result more efficient in eliminating dinoflagellates producing toxins. Azaspiracid-1 (AZA1) crosses the intestinal barrier in a dose- dependent manner causing alterations in intestinal epithelial cells. In vivo studies reveal highest toxicity for DTX1 and lowest for DTX2 with respect to OA, while a relationship between the diarreal effect of OA and its neuronal action is suggested in vitro. Besides, this is the first time that oral lethal dose 50 and NOAEL (No-Observed-Adverse-Effect-Level) values for TTX are established.