Cerebral toxicity of the trichothecene toxin T-2, of the products of its hydrolysis and of some related toxins. 1988

F Bergmann, and D Soffer, and B Yagen
Department of Pharmacology, Hebrew University-Hadassah Medical School, Jerusalem.

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.

UI MeSH Term Description Entries
D008297 Male Males
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D006868 Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012717 Sesquiterpenes Fifteen-carbon compounds formed from three isoprenoid units with general formula C15H24. Farnesanes,Farnesene,Farnesenes,Sesquiterpene,Sesquiterpene Derivatives,Sesquiterpenoid,Sesquiterpenoids,Derivatives, Sesquiterpene
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013605 T-2 Toxin A potent mycotoxin produced in feedstuffs by several species of the genus FUSARIUM. It elicits a severe inflammatory reaction in animals and has teratogenic effects. Fusaritoxin,Fusariotoxin,T-2 Toxin, alpha,4 beta-Isomer,T2 Toxin,T 2 Toxin,Toxin, T-2,Toxin, T2
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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