The Role of Gastrointestinal Microflora in the Metabolism and Toxicity of Trichothecene Mycotoxins
Swanson, Steven Philip
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https://hdl.handle.net/2142/71357
Description
Title
The Role of Gastrointestinal Microflora in the Metabolism and Toxicity of Trichothecene Mycotoxins
Author(s)
Swanson, Steven Philip
Issue Date
1988
Doctoral Committee Chair(s)
Buck, William B.
Department of Study
Veterinary Medical Science
Discipline
Veterinary Medical Science
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Veterinary Science
Abstract
The three trichothecene mycotoxins, T-2 toxin, diacetoxyscirpenol (DAS) and deoxynivalenol (DON) were incubated in vitro under anaerobic conditions with bovine rumen microorganisms. Gas chromatographic and gas chromatography/mass spectrometric analysis of the extracts demonstrated that all three toxins were biotransformed to a variety of deacylated, deepoxy products including: deepoxy deoxynivalenol (DOM-1), deepoxy monoacetoxyscirpenol (DE MAS), deepoxy scirpentriol (DE SCP), deepoxy HT-2 (DE HT-2) and deepoxy T-2 triol (DE TRIOL). Fecal microflora obtained from rats, cattle and swine biotransformed DAS to deacylated deepoxidation products including DE MAS and DE SCP. By contrast, fecal microflora from horses, dogs and chickens failed to produce deepoxy metabolites, yielding only deacylation products. Rat cecal microflora efficiently biotransformed T-2, DAS and the polar trichothecenes, tetraol and scirpentriol, to their deepoxy metabolites demonstrating that lipid solubility is not a major factor in epoxide reduction.
The metabolites DE HT-2, DE TRIOL, DE MAS and DE SCP were prepared in milligram quantities by fermentation of T-2 or DAS with bovine rumen microorganisms under anaerobic conditions. Deepoxy T-2 tetraol was produced by alkaline hydrolysis of DE HT-2. Purification was accomplished with both normal and reverse phase HPLC. Deepoxy T-2 was synthesized from T-2 toxin with n-butyl lithium and tungsten hexachloride.
The toxicity of the deacylated deepoxy trichothecenes was compared to their epoxy analogs using a brine shrimp bioassay system. In all cases the deepoxy metabolites were significantly less toxic than the corresponding epoxy congeners. Deepoxy T-2 was demonstrated to be non toxic to mice at dosages administered intraperitoneally up to 60 mg/kg, and at least 400 times less toxic than T-2 toxin in the rat skin irritation bioassay.
Two different types of anti T-2 antibodies were examined for cross-reactivity to several T-2 metabolites. Both HT-2 and DE HT-2 cross-reacted with monoclonal antibody 15H6 to a greater extent than T-2 toxin. Rabbit polyclonal T-2 antibodies displayed greater specificity to T-2 toxin compared to the monoclonal antibody.
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