Cytotoxic effects and degradation products of three mycotoxins: Alternariol, 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol in liver hepatocellular carcinoma cells

Juan-García, Ana; König, Stefanie; Ruiz, María-José

doi:10.1016/j.toxlet.2015.03.003

Cited by 41 publications

(24 citation statements)

References 34 publications

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“…However, no such discrimination between 3ADON and 15ADON is observed with the digestive enzymes, T84 cells and renal S9 fraction. Interestingly, preferential deacetylation of 3ADON compared to 15ADON has also been reported in HepG2 by others [33], in plant cells [34,35] and in vivo with chickens since exposure to 15ADON, but not 3ADON, results in some acetylated form being detected into their blood [21]. At this stage, the reason of this selectivity remains unknown but could rely on an easier access and/or higher affinity of 3ADON compared to 15ADON for the catalytic site of the enzyme(s) responsible of their deacetylation.…”

Section: Discussionmentioning

confidence: 57%

Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches

Ajandouz

Berdah

Moutardier

et al. 2016

Toxins

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In addition to deoxynivalenol (DON), acetylated derivatives, i.e., 3-acetyl and 15-acetyldexynivalenol (or 3/15ADON), are present in cereals leading to exposure to these mycotoxins. Animal and human studies suggest that 3/15ADON are converted into DON after their ingestion through hydrolysis of the acetyl moiety, the site(s) of such deacetylation being still uncharacterized. We used in vitro and ex vivo approaches to study the deacetylation of 3/15ADON by enzymes and cells/tissues present on their way from the food matrix to the blood in humans. We found that luminal deacetylation by digestive enzymes and bacteria is limited. Using human cells, tissues and S9 fractions, we were able to demonstrate that small intestine and liver possess strong deacetylation capacity compared to colon and kidneys. Interestingly, in most cases, deacetylation was more efficient for 3ADON than 15ADON. Although we initially thought that carboxylesterases (CES) could be responsible for the deacetylation of 3/15ADON, the use of pure human CES1/2 and of CES inhibitor demonstrated that CES are not involved. Taken together, our original model system allowed us to identify the small intestine and the liver as the main site of deacetylation of ingested 3/15ADON in humans.

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Section: Discussionmentioning

confidence: 57%

Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches

Ajandouz

Berdah

Moutardier

et al. 2016

Toxins

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“…We are only aware of one previous study indicating that this pathway seems to exist for DON. 47 In our experiment, we found two isomers of DON-10-GSH and DON-10cysteine. The fragmentation pattern indicates that both were conjugated at position C-10 via Michael addition.…”

Section: Don-gsh and Related Metabolites A Common Phase IIsupporting

confidence: 47%

Stable Isotope-Assisted Metabolomics for Deciphering Xenobiotic Metabolism in Mammalian Cell Culture

Flasch¹,

Bueschl²,

Woelflingseder³

et al. 2020

Preprint

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We present a workflow based on stable isotope-assisted metabolomics and the bioinformatics tool MetExtract II for deciphering xenobiotic metabolites produced by human cells. Its potential was demonstrated by the investigation of the metabolism of deoxynivalenol (DON), an abundant food contaminatn, in a liver cracinoma cell line (HeoG2) and a model for colon carcinoma (HT29). Detected known metabolites included DON-3-sulfate, DON-10-sulfonate, and DON-10-glutathione as well as DON-cysteine. Conjugation with amino acids and antibiotics was confirmed for the first time. The approach allows the untargeted elucidation of human xenobiotic products in tissue culture.<br>

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“…However, glutathione-conjugate formation of DON has not been recognized as mammalian detoxification mechanism so far. We are only aware of one previous study indicating that this pathway seems to exist for DON (Juan-García et al 2015). In our experiment, we found two isomers of DON-10-GSH and DON-10-Cys.…”

Section: Don-gsh and Related Metabolitesmentioning

confidence: 51%

Stable Isotope-Assisted Metabolomics for Deciphering Xenobiotic Metabolism in Mammalian Cell Culture

Flasch¹,

Bueschl²,

Woelflingseder³

et al. 2019

Preprint

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Cytotoxic effects and degradation products of three mycotoxins: Alternariol, 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol in liver hepatocellular carcinoma cells

Cited by 41 publications

References 34 publications

Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches

Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches

Stable Isotope-Assisted Metabolomics for Deciphering Xenobiotic Metabolism in Mammalian Cell Culture

Stable Isotope-Assisted Metabolomics for Deciphering Xenobiotic Metabolism in Mammalian Cell Culture

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