Advances in Deoxynivalenol Toxicity Mechanisms: The Brain as a Target

Bonnet, M; Roux, Julien; Mounien, Lourdes; Dallaporta, Michel; Troadec, Jean‐Denis

doi:10.3390/toxins4111120

Cited by 88 publications

(85 citation statements)

References 101 publications

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“…In vivo studies have shown that DON affects the activity of brain neurons, particularly in relation to anorexia and emesis; exposure of pigs to 10–75 or >150 µg of DON/kg BW (body weight)/day causing partial/total feed refusal or vomiting, respectively (for review: [153]). Importantly, higher doses of DON are required in mice, i.e ., 0.5 to 5 mg/kg of BW causing anorexia, suggesting that pigs are more sensitive to brain effects than mice [153].…”

Section: Pathophysiological Effects Of Donmentioning

confidence: 99%

From the Gut to the Brain: Journey and Pathophysiological Effects of the Food-Associated Trichothecene Mycotoxin Deoxynivalenol

Maresca

2013

Toxins

323

287

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Mycotoxins are fungal secondary metabolites contaminating food and causing toxicity to animals and humans. Among the various mycotoxins found in crops used for food and feed production, the trichothecene toxin deoxynivalenol (DON or vomitoxin) is one of the most prevalent and hazardous. In addition to native toxins, food also contains a large amount of plant and fungal derivatives of DON, including acetyl-DON (3 and 15ADON), glucoside-DON (D3G), and potentially animal derivatives such as glucuronide metabolites (D3 and D15GA) present in animal tissues (e.g., blood, muscle and liver tissue). The present review summarizes previous and very recent experimental data collected in vivo and in vitro regarding the transport, detoxification/metabolism and physiological impact of DON and its derivatives on intestinal, immune, endocrine and neurologic functions during their journey from the gut to the brain.

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Section: Pathophysiological Effects Of Donmentioning

confidence: 99%

From the Gut to the Brain: Journey and Pathophysiological Effects of the Food-Associated Trichothecene Mycotoxin Deoxynivalenol

Maresca

2013

Toxins

323

287

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Section: Introductionmentioning

confidence: 99%

“…DON exerts a range of toxic effects in mammals and humans, e.g., on the intestine, the immune system and the brain [2,3]. The effects on the brain have been linked to the observed emesis and feed refusal in pigs [2]. Conjugation of DON with L-glutathione (GSH) was recently shown to be a biotransformation pathway in wheat plants that were injected with DON in controlled trials [4,5].…”

Section: Introductionmentioning

confidence: 99%

Glutathione-Conjugates of Deoxynivalenol in Naturally Contaminated Grain Are Primarily Linked via the Epoxide Group

Uhlig

Stanic

Hofgaard

et al. 2016

Toxins

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A glutathione (GSH) adduct of the mycotoxin 4-deoxynivalenol (DON), together with a range of related conjugates, has recently been tentatively identified by LC-MS of DON-treated wheat spikelets. In this study, we prepared samples of DON conjugated at the 10- and 13-positions with GSH, Cys, CysGly, γ-GluCys and N-acetylcysteine (NAC). The mixtures of conjugates were used as standards for LC-HRMS analysis of one of the DON-treated wheat spikelet samples, as well as 19 Norwegian grain samples of spring wheat and 16 grain samples of oats that were naturally-contaminated with DON at concentrations higher than 1 mg/kg. The artificially-contaminated wheat spikelets contained conjugates of GSH, CysGly and Cys coupled at the olefinic 10-position of DON, whereas the naturally-contaminated harvest-ripe grain samples contained GSH, CysGly, Cys, and NAC coupled mainly at the 13-position on the epoxy group. The identities of the conjugates were confirmed by LC-HRMS comparison with authentic standards, oxidation to the sulfoxides with hydrogen peroxide, and examination of product-ion spectra from LC-HRMS/MS analysis. No γ-GluCys adducts of DON were detected in any of the samples. The presence of 15-O-acetyl-DON was demonstrated for the first time in Norwegian grain. The results indicate that a small but significant proportion of DON is metabolized via the GSH-conjugation pathway in plants. To our knowledge, this is the first report of in vivo conjugation of trichothecenes via their epoxy group, which has generally been viewed as unreactive. Because conjugation at the 13-position of DON and other trichothecenes has been shown to be irreversible, this type of conjugate may prove useful as a biomarker of exposure to DON and other 12,13-epoxytrichothecenes.

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“…In 2001, the Joint Food and Agriculture Organization/ World Health Organization (FAO/WHO) Expert Committee on Food Additives (JECFA) proposed a provisional maximum tolerable daily intake (PMTDI) for DON of 1 µg/kg body weight (bw) based on the growth effects associated with DON exposure (8,27,28). In the following decade, investigations into the mechanisms of the effect of DON on weight gain were pursued and understood (8,9,(29)(30)(31)(32). In 2010, JECFA extended the PMTDI to apply to both DON and its acetylated derivatives and concluded that mean estimates of national exposure to DON were below the PMTDI of 1 µg/kg bw (8,27,28).…”

Section: Introductionmentioning

confidence: 99%

DON Occurrence in Grains: A North American Perspective

Bianchini

Horsley

Jack³

et al. 2015

Cereal Foods World

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In agricultural commodities, the occurrence of deoxynivalenol (DON) has been reported all over the world, with levels varying among grain types and years of production. The grain supply chain, including growers, buyers, and end users, have effectively managed DON with strategies to control this issue systematically. The safety of consumers is ensured through use of these management strategies. This is observed in this review of the North American systems. This article describes the occurrence and management of DON in North America, which is accomplished by 1) a review of the toxicological effects of DON; 2) a review of publically available data and introduction of new information regarding the occurrence of DON in wheat, maize, and barley in North America, including variability due to growing regions, grain varieties, and year of production; 3) an overview of industry practices to reduce DON contamination from field through milling when necessary; 4) a review of how all in the value chain, including growers, buyers, and end users, have effectively managed DON for more than 20 years; 5) a description of current maximum limits associated with DON; and 6) the economic impact of any potential changes in international regulations.

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Advances in Deoxynivalenol Toxicity Mechanisms: The Brain as a Target

Cited by 88 publications

References 101 publications

From the Gut to the Brain: Journey and Pathophysiological Effects of the Food-Associated Trichothecene Mycotoxin Deoxynivalenol

From the Gut to the Brain: Journey and Pathophysiological Effects of the Food-Associated Trichothecene Mycotoxin Deoxynivalenol

Glutathione-Conjugates of Deoxynivalenol in Naturally Contaminated Grain Are Primarily Linked via the Epoxide Group

DON Occurrence in Grains: A North American Perspective

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