Evidence map›Paper›PMID 28638985›Full record

ArticleArchives of toxicology2017

Glucuronidation of deoxynivalenol (DON) by different animal species: identification of iso-DON glucuronides and iso-deepoxy-DON glucuronides as novel DON metabolites in pigs, rats, mice, and cows.

Heidi E Schwartz-Zimmermann, Christian Hametner, Veronika Nagl, Iris Fiby, Lukas Macheiner, Janine Winkler, Sven Dänicke, Erica Clark, James J Pestka, Franz Berthiller

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Archives of toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
14.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 45 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Heidi E Schwartz-ZimmermannChristian Doppler Laboratory for Mycotoxin Metabolism, Department of Agrobiotechnology (IFA-Tulln), Center for Analytical Chemistry, University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430, Tulln, Austria. heidi.schwartz@boku.ac.at.
Christian HametnerInstitute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060, Vienna, Austria.
Veronika NaglChristian Doppler Laboratory for Mycotoxin Metabolism, Department of Agrobiotechnology (IFA-Tulln), Center for Analytical Chemistry, University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430, Tulln, Austria.
Iris FibyChristian Doppler Laboratory for Mycotoxin Metabolism, Department of Agrobiotechnology (IFA-Tulln), Center for Analytical Chemistry, University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430, Tulln, Austria.
Lukas MacheinerChristian Doppler Laboratory for Mycotoxin Metabolism, Department of Agrobiotechnology (IFA-Tulln), Center for Analytical Chemistry, University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430, Tulln, Austria.
Janine WinklerInstitute of Animal Nutrition, Friedrich-Loeffler-Institute (FLI), Federal Research Institute for Animal Health, 38116, Brunswick, Germany.
Sven DänickeInstitute of Animal Nutrition, Friedrich-Loeffler-Institute (FLI), Federal Research Institute for Animal Health, 38116, Brunswick, Germany.
Erica ClarkDepartment of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, 48824, USA.
James J PestkaDepartment of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, 48824, USA.
Franz BerthillerChristian Doppler Laboratory for Mycotoxin Metabolism, Department of Agrobiotechnology (IFA-Tulln), Center for Analytical Chemistry, University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430, Tulln, Austria.
BOKU University · ATFriedrich-Loeffler-Institut · DEMichigan State University · USTU Wien · AT

Funding

USDA Wheat and Scab Initiative Award 59-0206-9-058
6 · The paper itself

Abstract

The Fusarium mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereal-based food and feed. Mammals metabolize DON by conjugation to glucuronic acid (GlcAc), the extent and regioselectivity of which is species-dependent. So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. In the present work, qualitative HPLC-MS/MS analysis of urine samples of animals treated with DON (rats: 2 mg/kg bw, single bolus, gavage; mice: 1 mg/kg bw, single i.p. injection; pigs: 74 µg/kg bw, single bolus, gavage; cows: 5.2 mg DON/kg dry mass, oral for 13 weeks) revealed additional DON and deepoxy-DON (DOM) glucuronides. To elucidate their structures, DON and DOM were incubated with human (HLM) and rat liver microsomes (RLM). Besides the expected DON/DOM-3- and 15-GlcAc, minor amounts of four DON- and four DOM glucuronides were formed. Isolation and enzymatic hydrolysis of four of these compounds yielded iso-DON and iso-DOM, the identities of which were eventually confirmed by NMR. Incubation of iso-DON and iso-DOM with RLM and HLM yielded two main glucuronides for each parent compound, which were isolated and identified as iso-DON/DOM-3-GlcAc and iso-DON/DOM-8-GlcAc by NMR. Iso-DON-3-GlcAc, most likely misidentified as DON-7-GlcAc in the literature, proved to be a major DON metabolite in rats and a minor metabolite in pigs. In addition, iso-DON-8-GlcAc turned out to be one of the major DON metabolites in mice. DOM-3-GlcAc was the dominant DON metabolite in urine of cows and an important DON metabolite in rat urine. Iso-DOM-3-GlcAc was detected in urine of DON-treated rats and cows. Finally, DON-8,15-hemiketal-8-glucuronide, a previously described by-product of DON-3-GlcAc production by RLM, was identified in urine of DON-exposed mice and rats. The discovery of several novel DON-derived glucuronides in animal urine requires adaptation of the currently used methods for DON-biomarker analysis.

Indexed as

AnimalsCattleChromatography, High Pressure LiquidGlucuronidesHumansHydrolysisMiceMicrosomes, LiverRatsSwineTandem Mass SpectrometryTrichothecenesdeepoxy-deoxynivalenoldeoxynivalenoldeoxynivalenol-3-glucuronideGlucuronidesTrichothecenesCyclic hemiketal DON 8-O-β-D-glucuronideHigh-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS)Iso-deepoxy-deoxynivalenolIso-deoxynivalenolMetabolism

Identifiers

PMID28638985
PMCPMC5719127
OpenAlexW2710306050

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.