Cerebral toxicity of the trichothecene toxin T-2, of the products of its hydrolysis and of some related toxins.
T-2 toxin and its metabolites (resulting from enzymatic hydrolysis by rat brain homogenate) were applied to the midbrain of albino rats, either in solid form or dissolved in dimethyl sulfoxide (DMSO). Solid implants of HT-2 toxin and of T-2 triol were lethal in the range of 10-20 micrograms per rat, i.e. similar to the effect of T-2 toxin itself. For four further trichothecenes, the following decreasing order of toxicities was found: T-2 tetraol = iso-T-2 toxin greater than T-2 tetraol tetraacetate greater than T-2 toxin acetate. Implants of the last compound were the least toxic in the present series of trichothecenes; its LD50 value was nearly ten times higher than that of T-2 toxin. A similar gradation of toxicity was observed upon intracerebral injection of the compounds dissolved in DMSO. Here the only exception was the markedly reduced toxicity of T-2 toxin itself. From these data, the role of free 3 alpha- and 4 beta-hydroxyl groups has been evaluated. For subcutaneous applications, the largest ratio of LD50 values was 5, i.e. for the pair T-2 triol-T-2 tetraol tetraacetate. Among the signs of central intoxication, convulsions, adipsia and aphagia were marked. Pathological changes in the brain tissue, mainly involving necrotic, hemorrhagic and inflammatory lesions at the sites of application, were similar for all trichothecenes tested in this study.
Bergmann
F
F
Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem.
Soffer
D
D
Yagen
B
B
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D006868:Hydrolysis; D008297:Male; D051381:Rats; D012717:Sesquiterpenes / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013605:T-2 Toxin / Q000378:metabolism / Q000633:toxicity*
D012717:Sesquiterpenes; D013605:T-2 Toxin