Trichothecene mycotoxins metabolism

Swanson, S.P. et ah. Metabolism of three trichothecene mycotoxins, T-2 toxin, diacetoxyscirpenol and deox5mivalenol, by bovine rumen microorganisms, J. Chromatogr., 414, 335, 1987. 

Swanson, S.P., Corley, R.A. (1989). The distribution, metabolism and excretion of trichothecene mycotoxins. In Trichothecene Mycotoxicosis Physiological Effects, Vol. 1 (V.R. Beasley, ed.), pp. 37-61. CRC Press, Boca Raton, FL. 

Compared with some of the other mycotoxins such as aflatoxin, the trichothecenes do not appear to require metabolic activation to exert their biological activity.50 After direct dermal application or oral ingestion, the trichothecene mycotoxins can cause rapid irritation to the skin or intestinal mucosa. In cell-free systems or single cells in culture, these mycotoxins cause a rapid inhibition of protein synthesis and polyribosomal disaggregation.35 47 50 Thus, we can postulate that the trichothecene mycotoxins have molecular capability of direct reaction with cellular components. Despite this direct effect, it is possible to measure the toxicokinetics and the metabolism of the trichothecene mycotoxins. 

Pharmacokinetic studies60,61 have demonstrated T-2 toxin in the plasma of animals that were administered this mycotoxin both intravascularly and by aerosol. As plasma concentrations of the parent trichothecene mycotoxin decrease, the deacylated and hydroxylated metabolites and their glucu-ronide conjugates rapidly appear and disappear from circulation. From these various observations, we can conclude that the pharmacokinetics of the trichothecene mycotoxins are functions of the rate of absorption into the general circulation, metabolism, tissue distribution, and excretion. 

Regardless of the route of administration or the species of animal tested, the trichothecene mycotoxins were rapidly metabolized and excreted in urine... 

Four hours after swine received intravenous tritium-labeled T-2 toxin, glucuronide conjugates represented 63% of the metabolic residues in urine, and 77% in bile.63 The formation of glucuronide conjugates generally results in the elimination of toxicological activity of xenobiotics, which in certain species could represent a major route of detoxification of trichothecene mycotoxins. 

Swanson SP, Helaszek C, Buck WB, Rood HDJ, Haschek WM. The role of intestinal microflora in the metabolism of trichothecene mycotoxins. Food Chem Toxicol. 1988 26(10) 823-830. 

Hesketh AR (1992) Metabolic Studies on the Transformation of Trichodiene to Trichothecene Mycotoxins. Mycotoxin Res 8 52... 

Tamm Ch, Breitenstein W (1980) The Biosynthesis of Trichothecene Mycotoxins. In Steyn PS (ed.) The Biosynthesis of Mycotoxins. A Study in Secondary Metabolism, p. 69. Academic Press, New York... 

Udell MN, Dewick PM (1989) Metabolic Conversions of Trichothecene Mycotoxins De-Esterification Reactions Using Cell-Free Extracts of Fusarium. Z Naturforsch 44C 660... 

Baldwin NCP, Bycroft BW, Dewick PM, Gilbert J (1986) Metabolic Conversions of Trichothecene Mycotoxins Biotransformation of 3-Acetyldeoxynivalenol into Fusarenone X. Z Naturforsch 41C 845... 

Ohta, M., Matsumoto, H., Ishii, K. and Ueno, Y. (1978). Metabolism of trichothecene mycotoxins. II. Substrate specificity of microsomal deacetylation of trichothecene. jJ. Biochem. 84, 697-706. 

Contamination occurs primarily in wheat, barley, rye, and maize. Type A trichothecenes include mainly T-2 toxin, HT-2, and diacetoxyscirpenol (DAS) mycotoxins of the group B include mainly 4-deoxynivalenol (DON), commonly known as vomitoxin, and nivalenol (NIV). Toxic effects include nausea, vomiting, visual disorder, vertigo, throat irritation, and feed refusal in farm animals. The most toxic is T-2, followed by DAS and NIV, with DON being the least toxic in acute toxicity studies but the most widespread in grains worldwide and therefore the most studied. Issues related to chemical and physical data, occurrence, toxicity, absorption, distribution, and metabolism of trichothecenes are reviewed in WHO (89) and IARC (34). Physicochemical data for some selected Fusarium toxins is given by Sydenham et al. (90). The molecular structures of the main trichothecenes are shown in Fig. 9. 

Mycotoxins are, in general, low molecular weight, non-antigenic fungal secondary metabolites formed by way of several metabolic pathways, e.g. the polyketide route (aflatoxins), the terpene route (trichothecenes), the amino acid... 

C22H32O8, Mr 424.49, light yellow oil. Mycotoxin of the tric(h)othecene group formed by various Fusa-rium species. It is also formed in the metabolism of T-2 toxin. In comparison to the latter, H. is about 3- to 10-times less toxic. Otherwise it exhibits the typical properties of the trichothecenes. LD50 (mouse i.p.) 9mg/kg. 

Trichothecenes are a group of mycotoxins produced as secondary metabolic products by various fungi of several genuses such as Fusarium, Trichoderma, Myrothecium, Trichothecium, Cephalosporium and Stachybotrys. 

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