Mechanisms of Action of Low Molecular Weight Toxins in the Cardiovascular System.

摘要

This contract (DAMD17-86-C-6075) was devoted to investigation of mechanisms by which T-2 toxin, Roridin A, and other low molecular weight toxins exert toxic effects on the mammalian cardiovascular system. In year 02 we were granted permission by USAMRDC, to complete work on trichothecenes and phase in experiments to determine mechanisms of action of other low molecular weight toxins in cardiac cells. The majority of the second year was occupied by analysis of data obtained in earlier experiments. With respect to trichothecene toxicity, our data confirmed the hypothesis that cardiovascular complications mainly result from imbalance within the autonomic nervous system; the imbalance is caused by direct effects on autonomic neurons. With respect to the toxins known as tetrodotoxin (TTX), batrachatoxin (BTX), and veratridine, each of which binds to sodium channels in excitable cell membranes, our data suggest that BTX and veratridine can promote opening of cardiac sodium channels and that TTX promotes their closure. Keywords: Cardiovascular, Trichothecenes, Lab animals. (jes)