Preparation and characterization of the deepoxy trichothecenes: deepoxy HT-2, deepoxy T-2 triol, deepoxy T-2 tetraol, deepoxy 15-monoacetoxyscirpenol, and deepoxy scirpentriol

Swanson, Steven; Rood, Harold D; Behrens, J C; Sanders, Phillip E.

doi:10.1128/aem.53.12.2821-2826.1987

Cited by 48 publications

(26 citation statements)

References 31 publications

(31 reference statements)

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“…As representative example Table 3 shows the results for norNIV C. These findings are in agreement with the fact that the epoxy-group plays an important role in the toxicity of trichothecenes [14,15] using the 5-bromo-29-deoxyuridine incorporation assay accessing DNA synthesis showed that the de-epoxides of DON and NIV were 24 and 51 times less toxic compared to the toxins with an intact epoxide ring [15]. It was also shown in the brine shrimp bioassay that the de-epoxides are much less acutely toxic than the corresponding trichothecenes [16]. Furthermore, in the case of the T2 trichothecene i.p.…”

Section: Resultssupporting

confidence: 86%

Structural elucidation and analysis of thermal degradation products of theFusarium mycotoxin nivalenol

Bretz

Knecht

Göckler

et al. 2005

Mol. Nutr. Food Res.

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The major class of mycotoxins produced by Fusarium moulds are trichothecenes, a large group of sesquiterpenes sharing the same basic chemical structure, a 12,13-epoxytrichothec-9-ene ring system. Their toxic effects range from causing diarrhoea, vomiting and gastro-intestinal inflammation to noncompetitive inhibition of the biosynthesis of proteins in eukaryotic cells. Trichothecenes in general are relatively stable compounds, their degradation is observed only at high temperatures and prolonged heating time. In order to investigate the stability of the trichothecene nivalenol (NIV) under food processing conditions such as cooking or baking, we performed model heating experiments and screened the residue for degradation products using gas chromatography-mass spectrometry (GC-MS). Heating of nivalenol, especially under mild alkaline conditions, gave a mixture of four compounds (norNIV A, norNIV B, norNIV C, and NIV lactone), which where isolated and identified by nuclear magnetic resonance (NMR) and MS experiments. Although their formation was also demonstrated in heating experiments with spiked flour samples, only norNIV B was detectable in a screening of several commercially available samples, possibly due to the very low contamination with nivalenol. Furthermore, cell culture experiments using immortalized human kidney epithelial (IHKE) cells showed that the four compounds are less cytotoxic (formazan dye cytotoxicity assay) compared to nivalenol. Whereas nivalenol revealed an EC50 at 0.9 micromol, all other compounds did not show any significant effect up to 100 micromol.

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Section: Resultssupporting

confidence: 86%

Structural elucidation and analysis of thermal degradation products of theFusarium mycotoxin nivalenol

Bretz

Knecht

Göckler

et al. 2005

Mol. Nutr. Food Res.

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“…Deepoxy-DON is obtained after de-epoxidation of DON; several bacterial species and enzymes are able to catalyze this reaction 19 . The lower toxicity of deepoxy-DON, as compared to DON has been demonstrated in vitro on Swiss mouse 3T3 fibroblasts 16 , lymphocytes 17 and brine shrimp 25 . In vivo supplementation of DON-contaminated feed, with bacteria and/or an enzyme able to de-epoxidize DON, induced a reduction of the toxicity as shown by measurement of zootechnical or immune parameters 18 26 27 .…”

Section: Discussionmentioning

confidence: 96%

Microbial biotransformation of DON: molecular basis for reduced toxicity

Pierron

Mimoun

Murate

et al. 2016

Sci Rep

124

134

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Bacteria are able to de-epoxidize or epimerize deoxynivalenol (DON), a mycotoxin, to deepoxy-deoxynivalenol (deepoxy-DON or DOM-1) or 3-epi-deoxynivalenol (3-epi-DON), respectively. Using different approaches, the intestinal toxicity of 3 molecules was compared and the molecular basis for the reduced toxicity investigated. In human intestinal epithelial cells, deepoxy-DON and 3-epi-DON were not cytotoxic, did not change the oxygen consumption or impair the barrier function. In intestinal explants, exposure for 4 hours to 10 μM DON induced intestinal lesions not seen in explants treated with deepoxy-DON and 3-epi-DON. A pan-genomic transcriptomic analysis was performed on intestinal explants. 747 probes, representing 323 genes, were differentially expressed, between DON-treated and control explants. By contrast, no differentially expressed genes were observed between control, deepoxy-DON and 3-epi-DON treated explants. Both DON and its biotransformation products were able to fit into the pockets of the A-site of the ribosome peptidyl transferase center. DON forms three hydrogen bonds with the A site and activates MAPKinases (mitogen-activated protein kinases). By contrast deepoxy-DON and 3-epi-DON only form two hydrogen bonds and do not activate MAPKinases. Our data demonstrate that bacterial de-epoxidation or epimerization of DON altered their interaction with the ribosome, leading to an absence of MAPKinase activation and a reduced toxicity.

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“…Few studies on the in vitro biotransformation of DAS in farm animals have been identified. DAS was incubated for 12, 24 and 48 h under anaerobic conditions in rumen fluids (Swanson et al., ). MAS, SCT and their deepoxide metabolites were detected in the incubates.…”

Section: Assessmentmentioning

confidence: 99%

Risk to human and animal health related to the presence of 4,15‐diacetoxyscirpenol in food and feed

Knutsen¹,

Alexander²,

Barregård³

et al. 2018

EFS2

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4,15-Diacetoxyscirpenol (DAS) is a mycotoxin primarily produced by Fusarium fungi and occurring predominantly in cereal grains. As requested by the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) assessed the risk of DAS to human and animal health related to its presence in food and feed. Very limited information was available on toxicity and on toxicokinetics in experimental and farm animals. Due to the limitations in the available data set, human acute and chronic health-based guidance values (HBGV) were established based on data obtained in clinical trials of DAS as an anticancer agent (anguidine) after intravenous administration to cancer patients. The CONTAM Panel considered these data as informative for the hazard characterisation of DAS after oral exposure. The main adverse effects after acute and repeated exposure were emesis, with a no-observed-adverse-effect level (NOAEL) of 32 lg DAS/kg body weight (bw), and haematotoxicity, with a NOAEL of 65 lg DAS/kg bw, respectively. An acute reference dose (ARfD) of 3.2 lg DAS/kg bw and a tolerable daily intake (TDI) of 0.65 lg DAS/kg bw were established. Based on over 15,000 occurrence data, the highest acute and chronic dietary exposures were estimated to be 0.8 and 0.49 lg DAS/kg bw per day, respectively, and were not of health concern for humans. The limited information for poultry, pigs and dogs indicated a low risk for these animals at the estimated DAS exposure levels under current feeding practices, with the possible exception of fattening chicken. Assuming similar or lower sensitivity than for poultry, the risk was considered overall low for other farm and companion animal species for which no toxicity data were available. In consideration of the similarities of several trichothecenes and the likelihood of co-exposure via food and feed, it could be appropriate to perform a cumulative risk assessment for this group of substances. Acknowledgments: The CONTAM Panel wishes to thank the hearing expert Chiara Dall'Asta, the WG member Hanspeter Naegeli and the EFSA staff member Mari Eskola for the support provided to this scientific output. The CONTAM Panel acknowledges all European competent institutions and other stakeholders that provided occurrence data on DAS in food and feed, and supported the data collection for the Comprehensive European Food Consumption database.

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Preparation and characterization of the deepoxy trichothecenes: deepoxy HT-2, deepoxy T-2 triol, deepoxy T-2 tetraol, deepoxy 15-monoacetoxyscirpenol, and deepoxy scirpentriol

Cited by 48 publications

References 31 publications

Structural elucidation and analysis of thermal degradation products of theFusarium mycotoxin nivalenol

Structural elucidation and analysis of thermal degradation products of theFusarium mycotoxin nivalenol

Microbial biotransformation of DON: molecular basis for reduced toxicity

Risk to human and animal health related to the presence of 4,15‐diacetoxyscirpenol in food and feed

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