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Wulf-Dieter Moll
BIOMIN Research Center, BIOMIN, Technopark 1, 3430, Tulln, Austria

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Journal article
Published: 05 November 2020 in Food Control
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Fumonisin esterase FumD (EC 3.1.1.87), FUMzyme® (BIOMIN, Austria), effectively detoxifies fumonisin B mycotoxins (FB) by hydrolysis and removal of the tricarballylic acid groups. The current study evaluated FumD detoxification of total FB (FBT) in commercial maize utilising an experimental dry milling plant by introducing the enzyme during the kernel conditioning stage. Total FB and the hydrolysed product of FB1, HFB1, in maize and milling products were determined by LC-MS/MS. During maize conditioning of 4 h 10 min substantial FB1 hydrolysis was achieved between 1 and 4 U FumD/100 g maize. Complete conversion into HFB1 was delayed and only achieved at the highest enzyme concentration (32 U/100 g maize) reaching a 1:1 M conversion ratio. Dry milling of maize containing 3.29 ± 0.20 μmole FBT/kg (2354 ± 140 μg/kg) in the absence of FumD, resulted in a 2.5-fold increase in the FBT concentration in total hominy feed (8.34 ± 0.22 μmol/kg) (5979 ± 158 μg/kg) compared to the levels that prevail in Super (0.52 ± 0.07 μmol/kg) (347 ± 48 μg/kg) and Special (1.70 ± 0.01 μmol/kg) (1213 ± 8 μg/kg) maize meal, and Semolina (1.07 ± 0.14 μmol/kg) (765 ± 100 μg/kg) milling products. Introduction of FumD (40 U/kg) mainly impacted the total hominy feed product (germ + hominy milling fractions), constituting up to 30% of the reconstituted whole maize. A 99% reduction in FBT was obtained in total hominy feed, 48% in Semolina, 7% in Special maize meal, whereas no reduction was recorded in Super maize meal. FB1 reduction rates depend on the contamination level, kernel moisture and the diffusion rate from inner kernel layers to the kernel surface/aqueous interface. Risk modelling in children and adults indicated that FumD-treated whole maize and the resultant Semolina milling product intended for human consumption reduces the risk of exposure to FBT. However, no reduction in the exposure risk was observed when considering the Super and Special maize meal milling products. FB reduction in total hominy feed could open up new applications, such as its dietary incorporation as a source of fibre, minerals and bioactive plant constituents in maize-based food. In addition, the animal feed industry and subsistence maize farming communities using rudimentary milling processes, could also benefit.

ACS Style

Johanna F. Alberts; Ibtisaam Davids; Wulf-Dieter Moll; Gerd Schatzmayr; Hester-Mari Burger; Gordon S. Shephard; Wentzel C.A. Gelderblom. Enzymatic detoxification of the fumonisin mycotoxins during dry milling of maize. Food Control 2020, 123, 107726 .

AMA Style

Johanna F. Alberts, Ibtisaam Davids, Wulf-Dieter Moll, Gerd Schatzmayr, Hester-Mari Burger, Gordon S. Shephard, Wentzel C.A. Gelderblom. Enzymatic detoxification of the fumonisin mycotoxins during dry milling of maize. Food Control. 2020; 123 ():107726.

Chicago/Turabian Style

Johanna F. Alberts; Ibtisaam Davids; Wulf-Dieter Moll; Gerd Schatzmayr; Hester-Mari Burger; Gordon S. Shephard; Wentzel C.A. Gelderblom. 2020. "Enzymatic detoxification of the fumonisin mycotoxins during dry milling of maize." Food Control 123, no. : 107726.

Journal article
Published: 16 April 2020 in Toxins
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Ochratoxin A (OTA), a mycotoxin that is of utmost concern in food and feed safety, is produced by fungal species that mainly belong to the Aspergillus and Penicillium genera. The development of mitigation strategies to reduce OTA content along the supply chains is key to ensuring safer production of food and feed. Enzyme-based strategies are among the most promising methods due to their specificity, efficacy, and multi-situ applicability. In particular, some enzymes are already known for hydrolyzing OTA into ochratoxin alpha (OTα) and phenylalanine (Phe), eventually resulting in detoxification action. Therefore, the discovery of novel OTA hydrolyzing enzymes, along with the advancement of an innovative approach for their identification, could provide a broader basis to develop more effective mitigating strategies in the future. In the present study, a hybrid in silico/in vitro workflow coupling virtual screening with enzymatic assays was applied in order to identify novel OTA hydrolyzing enzymes. Among the various hits, porcine carboxypeptidase B was identified for the first time as an effective OTA hydrolyzing enzyme. The successful experimental endorsement of findings of the workflow confirms that the presented strategy is suitable for identifying novel OTA hydrolyzing enzymes, and it might be relevant for the discovery of other mycotoxin- mitigating enzymes.

ACS Style

Luca Dellafiora; Christoph Gonaus; Barbara Streit; Gianni Galaverna; Wulf-Dieter Moll; Gudrun Vogtentanz; Gerd Schatzmayr; Chiara Dall’Asta; Shreenath Prasad. An In Silico Target Fishing Approach to Identify Novel Ochratoxin A Hydrolyzing Enzyme. Toxins 2020, 12, 258 .

AMA Style

Luca Dellafiora, Christoph Gonaus, Barbara Streit, Gianni Galaverna, Wulf-Dieter Moll, Gudrun Vogtentanz, Gerd Schatzmayr, Chiara Dall’Asta, Shreenath Prasad. An In Silico Target Fishing Approach to Identify Novel Ochratoxin A Hydrolyzing Enzyme. Toxins. 2020; 12 (4):258.

Chicago/Turabian Style

Luca Dellafiora; Christoph Gonaus; Barbara Streit; Gianni Galaverna; Wulf-Dieter Moll; Gudrun Vogtentanz; Gerd Schatzmayr; Chiara Dall’Asta; Shreenath Prasad. 2020. "An In Silico Target Fishing Approach to Identify Novel Ochratoxin A Hydrolyzing Enzyme." Toxins 12, no. 4: 258.

Journal article
Published: 10 September 2019 in Toxins
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Enzymatic detoxification has become a promising approach for control of mycotoxins postharvest in grains through modification of chemical structures determining their toxicity. In the present study fumonisin esterase FumD (EC 3.1.1.87) (FUMzyme®; BIOMIN, Tulln, Austria), hydrolysing fumonisin (FB) mycotoxins by de-esterification, was utilised to develop an enzymatic reduction method in a maize kernel enzyme incubation mixture. Efficacy of the FumD FB reduction method in "low" and "high" FB contaminated home-grown maize was compared by monitoring FB1 hydrolysis to the hydrolysed FB1 (HFB1) product utilising a validated LC-MS/MS analytical method. The method was further evaluated in terms of enzyme activity and treatment duration by assessing enzyme kinetic parameters and the relative distribution of HFB1 between maize kernels and the residual aqueous environment. FumD treatments resulted in significant reduction (≥80%) in "low" (≥1000 U/L, p < 0.05) and "high" (100 U/L, p < 0.05; ≥1000 U/L, p < 0.0001) FB contaminated maize after 1 h respectively, with an approximate 1:1 µmol conversion ratio of FB1 into the formation of HFB1. Enzyme kinetic parameters indicated that, depending on the activity of FumD utilised, a significantly (p < 0.05) higher FB1 conversion rate was noticed in "high" FB contaminated maize. The FumD FB reduction method in maize could find application in commercial maize-based practices as well as in communities utilising home-grown maize as a main dietary staple and known to be exposed above the tolerable daily intake levels.

ACS Style

Johanna Alberts; Gerd Schatzmayr; Wulf-Dieter Moll; Ibtisaam Davids; John Rheeder; Hester-Mari Burger; Gordon Shephard; Wentzel Gelderblom. Detoxification of the Fumonisin Mycotoxins in Maize: An Enzymatic Approach. Toxins 2019, 11, 523 .

AMA Style

Johanna Alberts, Gerd Schatzmayr, Wulf-Dieter Moll, Ibtisaam Davids, John Rheeder, Hester-Mari Burger, Gordon Shephard, Wentzel Gelderblom. Detoxification of the Fumonisin Mycotoxins in Maize: An Enzymatic Approach. Toxins. 2019; 11 (9):523.

Chicago/Turabian Style

Johanna Alberts; Gerd Schatzmayr; Wulf-Dieter Moll; Ibtisaam Davids; John Rheeder; Hester-Mari Burger; Gordon Shephard; Wentzel Gelderblom. 2019. "Detoxification of the Fumonisin Mycotoxins in Maize: An Enzymatic Approach." Toxins 11, no. 9: 523.

Journal article
Published: 20 August 2019 in Toxins
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Zearalenone (ZEN)-degrading enzymes are a promising strategy to counteract the negative effects of this mycotoxin in livestock. The reaction products of such enzymes need to be thoroughly characterized before technological application as a feed additive can be envisaged. Here, we evaluated the estrogenic activity of the metabolites hydrolyzed zearalenone (HZEN) and decarboxylated hydrolyzed zearalenone (DHZEN) formed by hydrolysis of ZEN by the zearalenone-lactonase Zhd101p. ZEN, HZEN, and DHZEN were tested in two in vitro models, the MCF-7 cell proliferation assay (0.01-500 nM) and an estrogen-sensitive yeast bioassay (1-10,000 nM). In addition, we compared the impact of dietary ZEN (4.58 mg/kg) and equimolar dietary concentrations of HZEN and DHZEN on reproductive tract morphology as well as uterine mRNA and microRNA expression in female piglets (n = 6, four weeks exposure). While ZEN increased cell proliferation and reporter gene transcription, neither HZEN nor DHZEN elicited an estrogenic response, suggesting that these metabolites are at least 50-10,000 times less estrogenic than ZEN in vitro. In piglets, HZEN and DHZEN did not increase vulva size or uterus weight. Moreover, RNA transcripts altered upon ZEN treatment (EBAG9, miR-135a-5p, miR-187-3p and miR-204-5p) were unaffected by HZEN and DHZEN. Our study shows that both metabolites exhibit markedly reduced estrogenicity in vitro and in vivo, and thus provides an important basis for further evaluation of ZEN-degrading enzymes.

ACS Style

Sebastian Fruhauf; Barbara Novak; Veronika Nagl; Matthias Hackl; Doris Hartinger; Valentina Rainer; Silvia Labudová; Gerhard Adam; Markus Aleschko; Wulf-Dieter Moll; Michaela Thamhesl; Bertrand Grenier. Biotransformation of the Mycotoxin Zearalenone to its Metabolites Hydrolyzed Zearalenone (HZEN) and Decarboxylated Hydrolyzed Zearalenone (DHZEN) Diminishes its Estrogenicity In Vitro and In Vivo. Toxins 2019, 11, 481 .

AMA Style

Sebastian Fruhauf, Barbara Novak, Veronika Nagl, Matthias Hackl, Doris Hartinger, Valentina Rainer, Silvia Labudová, Gerhard Adam, Markus Aleschko, Wulf-Dieter Moll, Michaela Thamhesl, Bertrand Grenier. Biotransformation of the Mycotoxin Zearalenone to its Metabolites Hydrolyzed Zearalenone (HZEN) and Decarboxylated Hydrolyzed Zearalenone (DHZEN) Diminishes its Estrogenicity In Vitro and In Vivo. Toxins. 2019; 11 (8):481.

Chicago/Turabian Style

Sebastian Fruhauf; Barbara Novak; Veronika Nagl; Matthias Hackl; Doris Hartinger; Valentina Rainer; Silvia Labudová; Gerhard Adam; Markus Aleschko; Wulf-Dieter Moll; Michaela Thamhesl; Bertrand Grenier. 2019. "Biotransformation of the Mycotoxin Zearalenone to its Metabolites Hydrolyzed Zearalenone (HZEN) and Decarboxylated Hydrolyzed Zearalenone (DHZEN) Diminishes its Estrogenicity In Vitro and In Vivo." Toxins 11, no. 8: 481.

Journal article
Published: 28 June 2019 in Scientific Reports
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The mycotoxin zearalenone (ZEN) poses a risk to animal health because of its estrogenic effects. Diagnosis of ZEN-induced disorders remains challenging due to the lack of appropriate biomarkers. In this regard, circulating microRNAs (small non-coding RNAs) have remarkable potential, as they can serve as indicators for pathological processes in tissue. Thus, we combined untargeted and targeted transcriptomics approaches to investigate the effects of ZEN on the microRNA expression in porcine uterus, jejunum and serum, respectively. To this end, twenty-four piglets received uncontaminated feed (Control) or feed containing 0.17 mg/kg ZEN (ZEN low), 1.46 mg/kg ZEN (ZEN medium) and 4.58 mg/kg ZEN (ZEN high). After 28 days, the microRNA expression in the jejunum remained unaffected, while significant changes in the uterine microRNA profile were observed. Importantly, 14 microRNAs were commonly and dose-dependently affected in both the ZEN medium and ZEN high group, including microRNAs from the miR-503 cluster (i.e. ssc-miR-424-5p, ssc-miR-450a, ssc-miR-450b-5p, ssc-miR-450c-5p, ssc-miR-503 and ssc-miR-542-3p). Predicted target genes for those microRNAs are associated with regulation of gene expression and signal transduction (e.g. cell cycle). Although the effects in serum were less pronounced, receiver operating characteristic analysis revealed that several microRNA ratios were able to discriminate properly between non-exposed and ZEN-exposed pigs (e.g. ssc-miR-135a-5p/ssc-miR-432-5p, ssc-miR-542-3p/ssc-miR-493-3p). This work sheds new light on the molecular mechanisms of ZEN, and fosters biomarker discovery.

ACS Style

Bertrand Grenier; Matthias Hackl; Susanna Skalicky; Michaela Thamhesl; Wulf-Dieter Moll; Roger Berrios; Gerd Schatzmayr; Veronika Nagl. MicroRNAs in porcine uterus and serum are affected by zearalenone and represent a new target for mycotoxin biomarker discovery. Scientific Reports 2019, 9, 1 -14.

AMA Style

Bertrand Grenier, Matthias Hackl, Susanna Skalicky, Michaela Thamhesl, Wulf-Dieter Moll, Roger Berrios, Gerd Schatzmayr, Veronika Nagl. MicroRNAs in porcine uterus and serum are affected by zearalenone and represent a new target for mycotoxin biomarker discovery. Scientific Reports. 2019; 9 (1):1-14.

Chicago/Turabian Style

Bertrand Grenier; Matthias Hackl; Susanna Skalicky; Michaela Thamhesl; Wulf-Dieter Moll; Roger Berrios; Gerd Schatzmayr; Veronika Nagl. 2019. "MicroRNAs in porcine uterus and serum are affected by zearalenone and represent a new target for mycotoxin biomarker discovery." Scientific Reports 9, no. 1: 1-14.

Immunotoxicology
Published: 31 August 2018 in Archives of Toxicology
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Deoxynivalenol (DON) is the most abundant trichothecene in food and feed. It causes both acute and chronic disorders of the human and animal intestine, liver and the immune system. The structural basis for the toxicity of DON has not been fully elucidated. Using the pig as a target and a model species for human, the toxicity of DON and its deepoxy-metabolite (DOM-1) was compared. Animals were exposed by gavage to 1 and 0.5 nmol toxin/kg b.w./day for 2 and 3 weeks respectively. Whatever the dose/duration, DOM-1 was less toxic than DON in terms of weight gain and emesis. In the 3-week experiment, animals were vaccinated with ovalbumin, and their immune response was analyzed in addition to tissue morphology, biochemistry and hematology. DON impaired the morphology of the jejunum and the ileum, reduced villi height, decreased E-cadherin expression and modified the intestinal expression of cytokines. Similarly, DON induced hepatotoxicity as indicated by the lesion score and the blood biochemistry. By contrast, DOM-1 only induced minimal intestinal toxicity and did not trigger hepatotoxicity. As far as the immune response was concerned, the effects of ingesting DOM-1 were similar to those caused by DON, as measured by histopathology of lymphoid organs, PCNA expression and the specific antibody response. Taken together, these data demonstrated that DOM-1, a microbial detoxification product of DON, was not toxic in the sensitive pig model but retained some immune-modulatory properties of DON, especially its ability to stimulate a specific antibody response during a vaccination protocol.

ACS Style

Alix Pierron; Ana Paula Loureiro Bracarense; Anne-Marie Cossalter; Joëlle Laffitte; Heidi Schwartz-Zimmermann; Gerd Schatzmayr; Philippe Pinton; Wulf-Dieter Moll; Isabelle P. Oswald. Deepoxy-deoxynivalenol retains some immune-modulatory properties of the parent molecule deoxynivalenol in piglets. Archives of Toxicology 2018, 92, 3381 -3389.

AMA Style

Alix Pierron, Ana Paula Loureiro Bracarense, Anne-Marie Cossalter, Joëlle Laffitte, Heidi Schwartz-Zimmermann, Gerd Schatzmayr, Philippe Pinton, Wulf-Dieter Moll, Isabelle P. Oswald. Deepoxy-deoxynivalenol retains some immune-modulatory properties of the parent molecule deoxynivalenol in piglets. Archives of Toxicology. 2018; 92 (11):3381-3389.

Chicago/Turabian Style

Alix Pierron; Ana Paula Loureiro Bracarense; Anne-Marie Cossalter; Joëlle Laffitte; Heidi Schwartz-Zimmermann; Gerd Schatzmayr; Philippe Pinton; Wulf-Dieter Moll; Isabelle P. Oswald. 2018. "Deepoxy-deoxynivalenol retains some immune-modulatory properties of the parent molecule deoxynivalenol in piglets." Archives of Toxicology 92, no. 11: 3381-3389.

Journal article
Published: 01 December 2017 in Poultry Science
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Fumonisins (FB) are among the most frequently detected mycotoxins in feedstuffs and finished feed, and recent data suggest that the functions of the gastrointestinal tract (GIT) in poultry species might be compromised at doses ranging from 10 to 20 mg/kg, close to field incidences and below the US and EU guidelines. Strategies are therefore necessary to reduce the exposure of poultry to FB. In the present study, we assessed the efficacy of fumonisin esterase FumD (EC 3.1.1.87, commercial name FUMzyme®) to cleave the tricarballylic acid side chains of FB, leading to the formation of non-toxic hydrolyzed fumonisins in the GIT of broiler chickens. Broiler chickens were fed for 14 d (7 to 21 d of age) 3 different diets (6 birds/cage, 6 cages/diet), i) control feed (negative control group), ii) feed contaminated with 10 mg FB/kg (FB group), and iii) feed contaminated with 10 mg FB/kg and supplemented with 100 units of FUMzyme®/kg (FB+FUMzyme® group). To determine the degree of reduction of FB in the GIT, 2 characteristics were analyzed. First, the sphinganine-to-sphingosine ratio in the serum and liver was determined as a biomarker of effect for exposure to FB. Second, the concentration of fumonisin B1 and its hydrolyzed forms was evaluated in the gizzard, the proximal and distal parts of the small intestine, and the excreta. Significantly reduced sphinganine-to-sphingosine ratios in the serum and liver of the FB+FUMzyme® group (serum: 0.15 ± 0.01; liver: 0.17 ± 0.01) compared to the FB group (serum: 0.20 ± 0.01; liver: 0.29 ± 0.03) proved that supplementation of broiler feed with FUMzyme® was effective in partially counteracting the toxic effect of dietary FB. Likewise, FB concentrations in digesta and excreta were significantly reduced in the FB+FUMzyme® group compared to the FB group (P < 0.05; up to 75%). FUMzyme® furthermore partially counteracted FB-induced up-regulation of cytokine gene expression (IL-8 and IL-10) in the jejunum. The FB group showed significantly higher gene expression of IL-8 and IL-10 compared to the negative control group (IL-8: fold change = 2.9 ± 1.1, P < 0.05; IL-10: fold change = 3.6 ± 1.4, P < 0.05), whereas IL-8 and IL-10 mRNA levels were not significantly different in the FB+FUMzyme®® group compared to the other 2 groups. In conclusion, FUMzyme® is suitable to detoxify FB in chickens and maintain gut functions.

ACS Style

B Grenier; Heidi Schwartz-Zimmermann; C Gruber-Dorninger; I Dohnal; M Aleschko; G Schatzmayr; Wulf-Dieter Moll; T J Applegate. Enzymatic hydrolysis of fumonisins in the gastrointestinal tract of broiler chickens. Poultry Science 2017, 96, 4342 -4351.

AMA Style

B Grenier, Heidi Schwartz-Zimmermann, C Gruber-Dorninger, I Dohnal, M Aleschko, G Schatzmayr, Wulf-Dieter Moll, T J Applegate. Enzymatic hydrolysis of fumonisins in the gastrointestinal tract of broiler chickens. Poultry Science. 2017; 96 (12):4342-4351.

Chicago/Turabian Style

B Grenier; Heidi Schwartz-Zimmermann; C Gruber-Dorninger; I Dohnal; M Aleschko; G Schatzmayr; Wulf-Dieter Moll; T J Applegate. 2017. "Enzymatic hydrolysis of fumonisins in the gastrointestinal tract of broiler chickens." Poultry Science 96, no. 12: 4342-4351.

Journal article
Published: 06 July 2016 in Scientific Reports
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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.

ACS Style

Alix Pierron; Sabria Mimoun; Leticia S. Murate; Nicolas Loiseau; Yannick Lippi; Ana-Paula F. L. Bracarense; Gerd Schatzmayr; Jian Wei He; Ting Zhou; Wulf-Dieter Moll; Isabelle P. Oswald. Microbial biotransformation of DON: molecular basis for reduced toxicity. Scientific Reports 2016, 6, 29105 .

AMA Style

Alix Pierron, Sabria Mimoun, Leticia S. Murate, Nicolas Loiseau, Yannick Lippi, Ana-Paula F. L. Bracarense, Gerd Schatzmayr, Jian Wei He, Ting Zhou, Wulf-Dieter Moll, Isabelle P. Oswald. Microbial biotransformation of DON: molecular basis for reduced toxicity. Scientific Reports. 2016; 6 (1):29105.

Chicago/Turabian Style

Alix Pierron; Sabria Mimoun; Leticia S. Murate; Nicolas Loiseau; Yannick Lippi; Ana-Paula F. L. Bracarense; Gerd Schatzmayr; Jian Wei He; Ting Zhou; Wulf-Dieter Moll; Isabelle P. Oswald. 2016. "Microbial biotransformation of DON: molecular basis for reduced toxicity." Scientific Reports 6, no. 1: 29105.

Journal article
Published: 24 September 2015 in Archives of Toxicology
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Natural food contaminants such as mycotoxins are an important problem for human health. Deoxynivalenol (DON) is one of the most common mycotoxins detected in cereals and grains. Its toxicological effects mainly concern the immune system and the gastrointestinal tract. This toxin is a potent ribotoxic stressor leading to MAP kinase activation and inflammatory response. DON frequently co-occurs with its glucosylated form, the masked mycotoxin deoxynivalenol-3-β-d-glucoside (D3G). The toxicity of this later compound remains unknown in mammals. This study aimed to assess the ability of D3G to elicit a ribotoxic stress and to induce intestinal toxicity. The toxicity of D3G and DON (0–10 µM) was studied in vitro, on the human intestinal Caco-2 cell line, and ex vivo, on porcine jejunal explants. First, an in silico analysis revealed that D3G, contrary to DON, was unable to bind to the A-site of the ribosome peptidyl transferase center, the main targets for DON toxicity. Accordingly, D3G did not activate JNK and P38 MAPKs in treated Caco-2 cells and did not alter viability and barrier function on cells, as measured by the trans-epithelial electrical resistance. Treatment of intestinal explants for 4 h with 10 µM DON induced morphological lesions and up-regulated the expression of pro-inflammatory cytokines as measured by qPCR and pan-genomic microarray analysis. By contrast, expression profile of D3G-treated explants was similar to that of controls, and these explants did not show histomorphology alteration. In conclusion, our data demonstrated that glucosylation of DON suppresses its ability to bind to the ribosome and decreases its intestinal toxicity.

ACS Style

Alix Pierron; Sabria Mimoun; Leticia Sayuri Murate; Nicolas Loiseau; Yannick Lippi; Ana-Paula F. L. Bracarense; Laurence Liaubet; Gerd Schatzmayr; Franz Berthiller; Wulf-Dieter Moll; Isabelle P. Oswald. Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside. Archives of Toxicology 2015, 90, 2037 -2046.

AMA Style

Alix Pierron, Sabria Mimoun, Leticia Sayuri Murate, Nicolas Loiseau, Yannick Lippi, Ana-Paula F. L. Bracarense, Laurence Liaubet, Gerd Schatzmayr, Franz Berthiller, Wulf-Dieter Moll, Isabelle P. Oswald. Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside. Archives of Toxicology. 2015; 90 (8):2037-2046.

Chicago/Turabian Style

Alix Pierron; Sabria Mimoun; Leticia Sayuri Murate; Nicolas Loiseau; Yannick Lippi; Ana-Paula F. L. Bracarense; Laurence Liaubet; Gerd Schatzmayr; Franz Berthiller; Wulf-Dieter Moll; Isabelle P. Oswald. 2015. "Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-d-glucoside." Archives of Toxicology 90, no. 8: 2037-2046.

Journal article
Published: 13 April 2015 in Toxins
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In chickens, the effect of mycotoxins, especially fumonisins (FB), in the gastrointestinal tract (GIT) is not well documented. Thus, this study in broiler chicks determined the effects of consuming diets prepared with Fusarium verticillioides culture material containing FB on intestinal gene expression and on the sphinganine (Sa)/sphingosine (So) ratio (Sa/So; a biomarker of FB effect due to disruption of sphingolipid metabolism). Male broilers were assigned to 6 diets (6 cages/diet; 6 birds/cage) from hatch to 20 days containing 0.4, 5.6, 11.3, 17.5, 47.8, or 104.8 mg FB/kg diet. Exposure to FB altered the Sa/So ratio in all tissues analyzed, albeit to varying extents. Linear dose-responses were observed in the kidney, jejunum and cecum. The liver and the ileum were very sensitive and data fit a cubic and quadratic polynomial model, respectively. Gene expression in the small intestine revealed low but significant upregulations of cytokines involved in the pro-inflammatory, Th1/Th17 and Treg responses, especially at 10 days of age. Interestingly, the cecal tonsils exhibited a biphasic response. Unlike the sphingolipid analysis, the effects seen on gene expression were not dose dependent, even showing more effects when birds were exposed to 11.3 mg FB/kg. In conclusion, this is the first report on the disruption of the sphingolipid metabolism by FB in the GIT of poultry. Further studies are needed to reach conclusions on the biological meaning of the immunomodulation observed in the GIT, but the susceptibility of chickens to intestinal pathogens when exposed to FB, at doses lower than those that would cause overt clinical symptoms, should be addressed.

ACS Style

Bertrand Grenier; Heidi E. Schwartz-Zimmermann; Sylvia Caha; Wulf Dieter Moll; Gerd Schatzmayr; Todd J. Applegate. Dose-Dependent Effects on Sphingoid Bases and Cytokines in Chickens Fed Diets Prepared with Fusarium Verticillioides Culture Material Containing Fumonisins. Toxins 2015, 7, 1253 -1272.

AMA Style

Bertrand Grenier, Heidi E. Schwartz-Zimmermann, Sylvia Caha, Wulf Dieter Moll, Gerd Schatzmayr, Todd J. Applegate. Dose-Dependent Effects on Sphingoid Bases and Cytokines in Chickens Fed Diets Prepared with Fusarium Verticillioides Culture Material Containing Fumonisins. Toxins. 2015; 7 (4):1253-1272.

Chicago/Turabian Style

Bertrand Grenier; Heidi E. Schwartz-Zimmermann; Sylvia Caha; Wulf Dieter Moll; Gerd Schatzmayr; Todd J. Applegate. 2015. "Dose-Dependent Effects on Sphingoid Bases and Cytokines in Chickens Fed Diets Prepared with Fusarium Verticillioides Culture Material Containing Fumonisins." Toxins 7, no. 4: 1253-1272.

Journal article
Published: 28 March 2015 in BMC Microbiology
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Ergopeptines are a predominant class of ergot alkaloids produced by tall fescue grass endophyte Neotyphodium coenophialum or cereal pathogen Claviceps purpurea. The vasoconstrictive activity of ergopeptines makes them toxic for mammals, and they can be a problem in animal husbandry. We isolated an ergopeptine degrading bacterial strain, MTHt3, and classified it, based on its 16S rDNA sequence, as a strain of Rhodococcus erythropolis (Nocardiaceae, Actinobacteria). For strain isolation, mixed microbial cultures were obtained from artificially ergot alkaloid-enriched soil, and provided with the ergopeptine ergotamine in mineral medium for enrichment. Individual colonies derived from such mixed cultures were screened for ergotamine degradation by high performance liquid chromatography and fluorescence detection. R. erythropolis MTHt3 converted ergotamine to ergine (lysergic acid amide) and further to lysergic acid, which accumulated as an end product. No other tested R. erythropolis strain degraded ergotamine. R. erythropolis MTHt3 degraded all ergopeptines found in an ergot extract, namely ergotamine, ergovaline, ergocristine, ergocryptine, ergocornine, and ergosine, but the simpler lysergic acid derivatives agroclavine, chanoclavine, and ergometrine were not degraded. Temperature and pH dependence of ergotamine and ergine bioconversion activity was different for the two reactions. Degradation of ergopeptines to ergine is a previously unknown microbial reaction. The reaction end product, lysergic acid, has no or much lower vasoconstrictive activity than ergopeptines. If the genes encoding enzymes for ergopeptine catabolism can be cloned and expressed in recombinant hosts, application of ergopeptine and ergine degrading enzymes for reduction of toxicity of ergot alkaloid-contaminated animal feed may be feasible.

ACS Style

Michaela Thamhesl; Elisabeth Apfelthaler; Heidi Elisabeth Schwartz-Zimmermann; Elisavet Kunz-Vekiru; Rudolf Krska; Wolfgang Kneifel; Gerd Schatzmayr; Wulf-Dieter Moll. Rhodococcus erythropolis MTHt3 biotransforms ergopeptines to lysergic acid. BMC Microbiology 2015, 15, 73 .

AMA Style

Michaela Thamhesl, Elisabeth Apfelthaler, Heidi Elisabeth Schwartz-Zimmermann, Elisavet Kunz-Vekiru, Rudolf Krska, Wolfgang Kneifel, Gerd Schatzmayr, Wulf-Dieter Moll. Rhodococcus erythropolis MTHt3 biotransforms ergopeptines to lysergic acid. BMC Microbiology. 2015; 15 (1):73.

Chicago/Turabian Style

Michaela Thamhesl; Elisabeth Apfelthaler; Heidi Elisabeth Schwartz-Zimmermann; Elisavet Kunz-Vekiru; Rudolf Krska; Wolfgang Kneifel; Gerd Schatzmayr; Wulf-Dieter Moll. 2015. "Rhodococcus erythropolis MTHt3 biotransforms ergopeptines to lysergic acid." BMC Microbiology 15, no. 1: 73.

Journal article
Published: 01 February 2015 in Food and Chemical Toxicology
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Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in maize-based food and feed. Alkaline processing like nixtamalisation of maize generates partially and fully hydrolysed FB1 (pHFB1 and HFB1) and thermal treatment in the presence of reducing sugars leads to formation of N-(1-deoxy-D-fructos-1-yl) fumonisin B1 (NDF). The toxicity of these metabolites, in particular their effect on the sphingolipid metabolism, is either unknown or discussed controversially. We produced high purity FB1, pHFB1a+b, HFB1 and NDF and fed them to male Sprague Dawley rats for three weeks. Once a week, urine and faeces samples were collected over 24 h and analysed for fumonisin metabolites as well as for the sphinganine (Sa) to sphingosine (So) ratio by validated LC-MS/MS based methods. While the latter was significantly increased in the FB1 positive control group, the Sa/So ratios of the partially and fully hydrolysed fumonisins were indifferent from the negative control group. Although NDF was partly cleaved during digestion, the liberated amounts of FB1 did not raise the Sa/So ratio. These results show that the investigated alkaline and thermal processing products of FB1 were, at the tested concentrations, non-toxic for rats, and suggest that according food processing can reduce fumonisin toxicity for humans.

ACS Style

Irene Hahn; Veronika Nagl; Heidi Elisabeth Schwartz-Zimmermann; Elisabeth Varga; Christiane Schwarz; Veronika Slavik; Nicole Reisinger; Alexandra Malachová; Martina Cirlini; Silvia Generotti; Chiara Dall'Asta; Rudolf Krska; Wulf-Dieter Moll; Franz Berthiller. Effects of orally administered fumonisin B1 (FB1), partially hydrolysed FB1, hydrolysed FB1 and N-(1-deoxy-D-fructos-1-yl) FB1 on the sphingolipid metabolism in rats. Food and Chemical Toxicology 2015, 76, 11 -18.

AMA Style

Irene Hahn, Veronika Nagl, Heidi Elisabeth Schwartz-Zimmermann, Elisabeth Varga, Christiane Schwarz, Veronika Slavik, Nicole Reisinger, Alexandra Malachová, Martina Cirlini, Silvia Generotti, Chiara Dall'Asta, Rudolf Krska, Wulf-Dieter Moll, Franz Berthiller. Effects of orally administered fumonisin B1 (FB1), partially hydrolysed FB1, hydrolysed FB1 and N-(1-deoxy-D-fructos-1-yl) FB1 on the sphingolipid metabolism in rats. Food and Chemical Toxicology. 2015; 76 ():11-18.

Chicago/Turabian Style

Irene Hahn; Veronika Nagl; Heidi Elisabeth Schwartz-Zimmermann; Elisabeth Varga; Christiane Schwarz; Veronika Slavik; Nicole Reisinger; Alexandra Malachová; Martina Cirlini; Silvia Generotti; Chiara Dall'Asta; Rudolf Krska; Wulf-Dieter Moll; Franz Berthiller. 2015. "Effects of orally administered fumonisin B1 (FB1), partially hydrolysed FB1, hydrolysed FB1 and N-(1-deoxy-D-fructos-1-yl) FB1 on the sphingolipid metabolism in rats." Food and Chemical Toxicology 76, no. : 11-18.

Validation study
Published: 23 October 2014 in Analytical and Bioanalytical Chemistry
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Deoxynivalenol (DON) is a trichothecene mycotoxin regularly occurring in cereals. Rats are often used to study toxicokinetics of DON and related compounds, yet only about 30 % of the administered dose is typically recovered. Recently, it was reported that DON is partly metabolised to previously undetected DON- and deepoxy-DON (DOM) sulfonate in rats and tentative structures were proposed. The present work describes the production and characterisation of DON-, DOM- and DON-3-glucoside (D3G) sulfonates of three different series; the development and validation of liquid chromatography tandem mass spectrometry (LC-MS/MS)-based methods for determination of DON, DOM, D3G and their sulfonates in rat faeces and urine; and application of the methods to samples from a DON and D3G feeding trial with rats. In addition to previously produced DON sulfonates (DONS) 1, 2 and 3, D3G sulfonates 1, 2 and 3; and DOM sulfonates (DOMS) 2 and 3 were synthesised, purified and characterised. The developed methods showed apparent recoveries of all investigated compounds between 68 and 151 % in faeces and between 48 and 113 % in urine. The recovery of DON, D3G and their metabolites from faeces and urine of rats (n = 6) administered in a single dose of 2.0 mg/kg b.w. DON or the equimolar amount of D3G was 75 ± 9 % for the DON group and 68 ± 8 % for the D3G group. DON-, DOM- and D3G sulfonates excreted in faeces accounted for 48 and 47 % of the total amount of administered DON and D3G. Urinary excretion of sulfonates was DOMS 2 was predominant thereafter. The developed methods can also be used for investigation of DON (conjugate) sulfonate formation in other animal species. Graphical Abstract

ACS Style

Heidi E. Schwartz-Zimmermann; Christian Hametner; Veronika Nagl; Veronika Slavik; Wulf-Dieter Moll; Franz Berthiller. Deoxynivalenol (DON) sulfonates as major DON metabolites in rats: from identification to biomarker method development, validation and application. Analytical and Bioanalytical Chemistry 2014, 406, 7911 -7924.

AMA Style

Heidi E. Schwartz-Zimmermann, Christian Hametner, Veronika Nagl, Veronika Slavik, Wulf-Dieter Moll, Franz Berthiller. Deoxynivalenol (DON) sulfonates as major DON metabolites in rats: from identification to biomarker method development, validation and application. Analytical and Bioanalytical Chemistry. 2014; 406 (30):7911-7924.

Chicago/Turabian Style

Heidi E. Schwartz-Zimmermann; Christian Hametner; Veronika Nagl; Veronika Slavik; Wulf-Dieter Moll; Franz Berthiller. 2014. "Deoxynivalenol (DON) sulfonates as major DON metabolites in rats: from identification to biomarker method development, validation and application." Analytical and Bioanalytical Chemistry 406, no. 30: 7911-7924.

Journal article
Published: 01 July 2014 in New Biotechnology
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Julia Panhölzl; Julia Lindenberger; Patricia Menczik; Markus Aleschko; Irene Hahn; Heidi Schwartz-Zimmermann; Gerd Schatzmayr; Michaela Thamhesl; Wulf-Dieter Moll. Effect of gene copy number on production yield of recombinant ergopeptine hydrolase ErgA in Pichia pastoris. New Biotechnology 2014, 31, S188 .

AMA Style

Julia Panhölzl, Julia Lindenberger, Patricia Menczik, Markus Aleschko, Irene Hahn, Heidi Schwartz-Zimmermann, Gerd Schatzmayr, Michaela Thamhesl, Wulf-Dieter Moll. Effect of gene copy number on production yield of recombinant ergopeptine hydrolase ErgA in Pichia pastoris. New Biotechnology. 2014; 31 ():S188.

Chicago/Turabian Style

Julia Panhölzl; Julia Lindenberger; Patricia Menczik; Markus Aleschko; Irene Hahn; Heidi Schwartz-Zimmermann; Gerd Schatzmayr; Michaela Thamhesl; Wulf-Dieter Moll. 2014. "Effect of gene copy number on production yield of recombinant ergopeptine hydrolase ErgA in Pichia pastoris." New Biotechnology 31, no. : S188.

Journal article
Published: 01 July 2014 in New Biotechnology
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Corinna Kern; Markus Aleschko; Wulf-Dieter Moll; Gerd Schatzmayr. Purification of tag-free recombinant fumonisin esterase FumD from Pichia pastoris culture supernatant for use as calibration standard for enzyme quantification. New Biotechnology 2014, 31, S189 .

AMA Style

Corinna Kern, Markus Aleschko, Wulf-Dieter Moll, Gerd Schatzmayr. Purification of tag-free recombinant fumonisin esterase FumD from Pichia pastoris culture supernatant for use as calibration standard for enzyme quantification. New Biotechnology. 2014; 31 ():S189.

Chicago/Turabian Style

Corinna Kern; Markus Aleschko; Wulf-Dieter Moll; Gerd Schatzmayr. 2014. "Purification of tag-free recombinant fumonisin esterase FumD from Pichia pastoris culture supernatant for use as calibration standard for enzyme quantification." New Biotechnology 31, no. : S189.

Journal article
Published: 23 June 2014 in Toxicology Letters
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Plants can metabolize the Fusarium mycotoxin deoxynivalenol (DON) by forming the masked mycotoxin deoxynivalenol-3-β-d-glucoside (D3G). D3G might be cleaved during digestion, thus increasing the total DON burden of an individual. Due to a lack of invivo data, D3G has not been included in the various regulatory limits established for DON so far. The aim of our study was to contribute to the risk assessment of D3G by determination of its metabolism in pigs. Four piglets received water, D3G (116 μg/kg b.w.) and the equimolar amount of DON (75 μg/kg b.w.) by gavage on day 1, 5 and 9 of the experiment, respectively. Additionally, 15.5 μg D3G/kg b.w. were administered intravenously on day 13. Urine and feces were collected for 24 h and analyzed for DON, D3G, deoxynivalenol-3-glucuronide (DON-3-GlcA), deoxynivalenol-15-GlcA (DON-15-GlcA) and deepoxy-deoxynivalenol (DOM-1) by UHPLC–MS/MS. After oral application of DON and D3G, in total 84.8 ± 9.7% and 40.3 ± 8.5% of the given dose were detected in urine, respectively. The majority of orally administered D3G was excreted in form of DON, DON-15-GlcA, DOM-1 and DON-3-GlcA, while urinary D3G accounted for only 2.6 ± 1.4%. In feces, just trace amounts of metabolites were found. Intravenously administered D3G was almost exclusively excreted in unmetabolized form via urine. Data indicate that D3G is nearly completely hydrolyzed in the intestinal tract of pigs, while the toxin seems to be rather stable after systemic absorption. Compared to DON, the oral bioavailability of D3G and its metabolites seems to be reduced by a factor of up to 2, approximately.

ACS Style

Veronika Nagl; Bettina Woechtl; Heidi Schwartz-Zimmermann; Isabel Hennig-Pauka; Wulf-Dieter Moll; Gerhard Adam; Franz Berthiller. Metabolism of the masked mycotoxin deoxynivalenol-3-glucoside in pigs. Toxicology Letters 2014, 229, 190 -197.

AMA Style

Veronika Nagl, Bettina Woechtl, Heidi Schwartz-Zimmermann, Isabel Hennig-Pauka, Wulf-Dieter Moll, Gerhard Adam, Franz Berthiller. Metabolism of the masked mycotoxin deoxynivalenol-3-glucoside in pigs. Toxicology Letters. 2014; 229 (1):190-197.

Chicago/Turabian Style

Veronika Nagl; Bettina Woechtl; Heidi Schwartz-Zimmermann; Isabel Hennig-Pauka; Wulf-Dieter Moll; Gerhard Adam; Franz Berthiller. 2014. "Metabolism of the masked mycotoxin deoxynivalenol-3-glucoside in pigs." Toxicology Letters 229, no. 1: 190-197.

Research article
Published: 11 June 2013 in Journal of Agricultural and Food Chemistry
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Mycotoxin mitigation is of major interest as ingestion of mycotoxins results in poor animal health, decreased productivity, as well as substantial economic losses. A feed additive (FA) consisting of a combination of bacteria (Eubacterium BBSH797) and enzyme (fumonisin esterase FumD) was tested in pigs for its ability to neutralize the effects of mono- and co-contaminated diets with deoxynivalenol (DON) and fumonisins (FB) on hematology, biochemistry, tissue morphology, and immune response. Forty-eight animals, allocated into eight groups, received one of eight diets for 35 days: a control diet, a diet contaminated with either DON (3 mg/kg) or FB (6 mg/kg), or both toxins, and the same four diets with FA. Inclusion of FA restored the circulating number of neutrophils of piglets fed the FB and DON + FB diets. Similarly, FA counteracted the minor changes observed on plasma concentrations of albumin and creatinine. In lung, the lesions induced by the ingestion of FB in mono- and co-contaminated diets were no longer observed after addition of FA in these diets. Lesions recorded in the liver of pigs fed either of the contaminated diets with FA were partly reduced, and the increased hepatocyte proliferation was totally neutralized when FA was present in the co-contaminated diet. After 35 days of exposure, the development of the vaccinal response was significantly improved in animals fed diets supplemented with FA, as shown by results of lymphocyte proliferation, cytokine expression in spleen, and the production of specific Ig. Similarly, in jejunum of animals fed diets with FA, occurrence of lesions and upregulation of pro-inflammatory cytokines were much less obvious. The ameliorative effects provided by FA suggest that this approach would be suitable in the control of DON and FB that commonly co-occur in feed.

ACS Style

Bertrand Grenier; Ana Paula Loureiro Bracarense; Heidi Schwartz-Zimmermann; Joelma Lucioli; Anne-Marie Cossalter; Wulf-Dieter Moll; Gerd Schatzmayr; Isabelle Oswald. Biotransformation Approaches To Alleviate the Effects Induced by Fusarium Mycotoxins in Swine. Journal of Agricultural and Food Chemistry 2013, 61, 6711 -6719.

AMA Style

Bertrand Grenier, Ana Paula Loureiro Bracarense, Heidi Schwartz-Zimmermann, Joelma Lucioli, Anne-Marie Cossalter, Wulf-Dieter Moll, Gerd Schatzmayr, Isabelle Oswald. Biotransformation Approaches To Alleviate the Effects Induced by Fusarium Mycotoxins in Swine. Journal of Agricultural and Food Chemistry. 2013; 61 (27):6711-6719.

Chicago/Turabian Style

Bertrand Grenier; Ana Paula Loureiro Bracarense; Heidi Schwartz-Zimmermann; Joelma Lucioli; Anne-Marie Cossalter; Wulf-Dieter Moll; Gerd Schatzmayr; Isabelle Oswald. 2013. "Biotransformation Approaches To Alleviate the Effects Induced by Fusarium Mycotoxins in Swine." Journal of Agricultural and Food Chemistry 61, no. 27: 6711-6719.

Comparative study
Published: 18 September 2012 in Toxicology Letters
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Deoxynivalenol-3-β-d-glucoside (D3G), a plant metabolite of the Fusarium mycotoxin deoxynivalenol (DON), might be hydrolyzed in the digestive tract of mammals, thus contributing to the total dietary DON exposure of individuals. Yet, D3G has not been considered in regulatory limits set for DON for foodstuffs due to the lack of in vivo data. The aim of our study was to evaluate whether D3G is reactivated in vivo by investigation of its metabolism in rats. Six Sprague-Dawley rats received water, DON (2.0 mg/kg body weight (b.w.)) and the equimolar amount of D3G (3.1 mg/kg b.w.) by gavage on day 1, 8 and 15, respectively. Urine and feces were collected for 48 h and analyzed for D3G, DON, deoxynivalenol-glucuronide (DON-GlcA) and de-epoxy deoxynivalenol (DOM-1) by a validated LC–tandem mass spectrometry (MS/MS) based biomarker method. After administration of D3G, only 3.7 ± 0.7% of the given dose were found in urine in the form of analyzed analytes, compared to 14.9 ± 5.0% after administration of DON, and only 0.3 ± 0.1% were detected in the form of urinary D3G. The majority of administered D3G was recovered as DON and DOM-1 in feces. These results suggest that D3G is little bioavailable, hydrolyzed to DON during digestion, and partially converted to DOM-1 and DON-GlcA prior to excretion. Our data indicate that D3G is of considerably lower toxicological relevance than DON, at least in rats.

ACS Style

Veronika Nagl; Heidi Schwartz-Zimmermann; Rudolf Krska; Wulf-Dieter Moll; Siegfried Knasmüller; Mathias Ritzmann; Gerhard Adam; Franz Berthiller. Metabolism of the masked mycotoxin deoxynivalenol-3-glucoside in rats. Toxicology Letters 2012, 213, 367 -373.

AMA Style

Veronika Nagl, Heidi Schwartz-Zimmermann, Rudolf Krska, Wulf-Dieter Moll, Siegfried Knasmüller, Mathias Ritzmann, Gerhard Adam, Franz Berthiller. Metabolism of the masked mycotoxin deoxynivalenol-3-glucoside in rats. Toxicology Letters. 2012; 213 (3):367-373.

Chicago/Turabian Style

Veronika Nagl; Heidi Schwartz-Zimmermann; Rudolf Krska; Wulf-Dieter Moll; Siegfried Knasmüller; Mathias Ritzmann; Gerhard Adam; Franz Berthiller. 2012. "Metabolism of the masked mycotoxin deoxynivalenol-3-glucoside in rats." Toxicology Letters 213, no. 3: 367-373.

Journal article
Published: 01 September 2012 in New Biotechnology
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Sebastian Fruhauf; Elisavet Kunz-Vekiru; Gerd Schatzmayr; Wulf-Dieter Moll. Detection of hydrolyzed zearalenone (HZEN) as intermediate in Zearalenone catabolism of Clonostachys rosea. New Biotechnology 2012, 29, S167 .

AMA Style

Sebastian Fruhauf, Elisavet Kunz-Vekiru, Gerd Schatzmayr, Wulf-Dieter Moll. Detection of hydrolyzed zearalenone (HZEN) as intermediate in Zearalenone catabolism of Clonostachys rosea. New Biotechnology. 2012; 29 ():S167.

Chicago/Turabian Style

Sebastian Fruhauf; Elisavet Kunz-Vekiru; Gerd Schatzmayr; Wulf-Dieter Moll. 2012. "Detection of hydrolyzed zearalenone (HZEN) as intermediate in Zearalenone catabolism of Clonostachys rosea." New Biotechnology 29, no. : S167.

Journal article
Published: 15 May 2012 in Biochemical Pharmacology
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Fumonisins are mycotoxins frequently found as natural contaminants in maize, where they are produced by the plant pathogen Fusarium verticillioides. They are toxic to animals and exert their effects through mechanisms involving disruption of sphingolipid metabolism. Fumonisin B1 (FB1) is the predominant fumonisin in this family. FB1 is converted to its hydrolyzed analogs HFB1, by alkaline cooking (nixtamalization) or through enzymatic degradation. The toxicity of HFB1 is poorly documented especially at the intestinal level. The objectives of this study were to compare the toxicity of HFB1 and FB1 and to assess the ability of these toxins to disrupt sphingolipids biosynthesis. HFB1 was obtained by a deesterification of FB1 with a carboxylesterase. Piglets, animals highly sensitive to FB1, were exposed by gavage for 2 weeks to 2.8 μmol FB1 or HFB1/kg body weight/day. FB1 induced hepatotoxicity as indicated by the lesion score, the level of several biochemical analytes and the expression of inflammatory cytokines. Similarly, FB1 impaired the morphology of the different segments of the small intestine, reduced villi height and modified intestinal cytokine expression. By contrast, HFB1 did not trigger hepatotoxicity, did not impair intestinal morphology and slightly modified the intestinal immune response. This low toxicity of HFB1 correlates with a weak alteration of the sphinganine/sphingosine ratio in the liver and in the plasma. Taken together, these data demonstrate that HFB1 does not cause intestinal or hepatic toxicity in the sensitive pig model and only slightly disrupts sphingolipids metabolism. This finding suggests that conversion to HFB1 could be a good strategy to reduce FB1 exposure.

ACS Style

Bertrand Grenier; Ana-Paula F.L. Bracarense; Heidi Schwartz-Zimmermann; Catherine Trumel; Anne-Marie Cossalter; Gerd Schatzmayr; Martine Kolf-Clauw; Wulf-Dieter Moll; Isabelle Oswald. The low intestinal and hepatic toxicity of hydrolyzed fumonisin B1 correlates with its inability to alter the metabolism of sphingolipids. Biochemical Pharmacology 2012, 83, 1465 -1473.

AMA Style

Bertrand Grenier, Ana-Paula F.L. Bracarense, Heidi Schwartz-Zimmermann, Catherine Trumel, Anne-Marie Cossalter, Gerd Schatzmayr, Martine Kolf-Clauw, Wulf-Dieter Moll, Isabelle Oswald. The low intestinal and hepatic toxicity of hydrolyzed fumonisin B1 correlates with its inability to alter the metabolism of sphingolipids. Biochemical Pharmacology. 2012; 83 (10):1465-1473.

Chicago/Turabian Style

Bertrand Grenier; Ana-Paula F.L. Bracarense; Heidi Schwartz-Zimmermann; Catherine Trumel; Anne-Marie Cossalter; Gerd Schatzmayr; Martine Kolf-Clauw; Wulf-Dieter Moll; Isabelle Oswald. 2012. "The low intestinal and hepatic toxicity of hydrolyzed fumonisin B1 correlates with its inability to alter the metabolism of sphingolipids." Biochemical Pharmacology 83, no. 10: 1465-1473.