Toxicological studies with trichothecenes, applied to the rat brain in vivo and in vitro

Abstract The trichothecene mycotoxins are secondary metabolites, produced by a variety of species of fungi, and are contaminating various agricultural commodities. The toxicity of the trichothecenes has been tested by several methods of systemic applications. The toxic effects of trichothecenes, introduced directly into the rat brain, are much more selective and specific than the toxic actions, evoked by peripheral applications. In vitro, the enzymatic conversion of T-2 toxin by brain homogenate is largely restricted, as compared to the metabolic changes in the mammalian body as a whole. In vivo, slight modifications of the substituents, attached to the fundamental ring system A-C of the trichothecenes, cause marked variations in cerebral toxicity. This is particularly noteworthy for the macrocyclic trichothecenes, where relatively small changes in the large ring D cause more than a hundred fold variation in toxicity.