<i>In Vitro</i> Phase I Metabolism of <i>cis</i>-Zearalenone

Drzymala, Sarah; Herrmann, A.; Maul, Ronald; Pfeifer, Dietmar; Garbe, Leif‐Alexander; Koch, Matthias

doi:10.1021/tx500312g

Cited by 17 publications

(13 citation statements)

References 21 publications

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“…In vitro experiments conducted on phase I metabolism of cis -ZEN in human and rat liver microsomes showed that the metabolic pathway of this form may be similar to that of trans -ZEN. α- cis -ZEL, produced during the metabolic pathway of cis -ZEL, may exhibit higher oestrogenicity than its isomer [ 169 ]. Although the estrogenic properties of ZEN are well described, much less is known on their interactions with other nuclear receptors.…”

Section: Toxicological Propertiesmentioning

confidence: 99%

Modified Fusarium Mycotoxins in Cereals and Their Products—Metabolism, Occurrence, and Toxicity: An Updated Review

et al. 2018

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Mycotoxins are secondary fungal metabolites, toxic to humans, animals and plants. Under the influence of various factors, mycotoxins may undergo modifications of their chemical structure. One of the methods of mycotoxin modification is a transformation occurring in plant cells or under the influence of fungal enzymes. This paper reviews the current knowledge on the natural occurrence of the most important trichothecenes and zearalenone in cereals/cereal products, their metabolism, and the potential toxicity of the metabolites. Only very limited data are available for the majority of the identified mycotoxins. Most studies concern biologically modified trichothecenes, mainly deoxynivalenol-3-glucoside, which is less toxic than its parent compound (deoxynivalenol). It is resistant to the digestion processes within the gastrointestinal tract and is not absorbed by the intestinal epithelium; however, it may be hydrolysed to free deoxynivalenol or deepoxy-deoxynivalenol by the intestinal microflora. Only one zearalenone derivative, zearalenone-14-glucoside, has been extensively studied. It appears to be more reactive than deoxynivalenol-3-glucoside. It may be readily hydrolysed to free zearalenone, and the carbonyl group in its molecule may be easily reduced to α/β-zearalenol and/or other unspecified metabolites. Other derivatives of deoxynivalenol and zearalenone are poorly characterised. Moreover, other derivatives such as glycosides of T-2 and HT-2 toxins have only recently been investigated; thus, the data related to their toxicological profile and occurrence are sporadic. The topics described in this study are crucial to ensure food and feed safety, which will be assisted by the provision of widespread access to such studies and obtained results.

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Section: Toxicological Propertiesmentioning

confidence: 99%

Modified Fusarium Mycotoxins in Cereals and Their Products—Metabolism, Occurrence, and Toxicity: An Updated Review

et al. 2018

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“…Cis-isomerisation of ZEN has been described to occur in the field as an effect of sunlight (Drzymala et al, 2014). As the current analytical methods do not include cis-ZEN, occurrence data in feed or raw material are still not available.…”

Section: Occurrence Of Modified Forms Of Zen In Feed From Plant Originmentioning

confidence: 99%

Risks for animal health related to the presence of zearalenone and its modified forms in feed

Knutsen¹,

Alexander²,

Barregård³

et al. 2017

EFS2

147

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Zearalenone (ZEN), a mycotoxin primarily produced by Fusarium fungi, occurs predominantly in cereal grains. The European Commission asked EFSA for a scientific opinion on the risk to animal health related to ZEN and its modified forms in feed. Modified forms of ZEN occurring in feed include phase I metabolites a-zearalenol (a-ZEL), b-zearalenol (b-ZEL), a-zearalanol (a-ZAL), b-zearalanol (b-ZAL), zearalanone (ZAN) and phase II conjugates. ZEN has oestrogenic activity and the oestrogenic activity of the modified forms of ZEN differs considerably. For ZEN, the EFSA Panel on Contaminants in the Food Chain (CONTAM) established no observed adverse effect levels (NOAELs) for pig (piglets and gilts), poultry (chicken and fattening turkeys), sheep and fish (extrapolated from carp) and lowest observed effect level (LOAEL) for dogs. No reference points could be established for cattle, ducks, goats, horses, rabbits, mink and cats. For modified forms, no reference points could be established for any animal species and relative potency factors previously established from rodents by the CONTAM Panel in 2016 were used. The dietary exposure was estimated on 17,706 analytical results with high proportions of left-censored data (ZEN about 60%, ZAN about 70%, others close to 100%). Samples for ZEN were collected between 2001 and 2015 in 25 different European countries, whereas samples for the modified forms were collected mostly between 2013 and 2015 from three Member States. Based on exposure estimates, the risk of adverse health effects of feed containing ZEN was considered extremely low for poultry and low for sheep, dog, pig and fish. The same conclusions also apply to the sum of ZEN and its modified forms.

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“…In order to widely estimate the effect of human metabolism on the activity of cis-ZEN, several computed metabolites and the phase-I human metabolites resolved so far (i.e. a-and b-cis-zearalenol) (Drzymala et al, 2014) have been analyzed herein for the capability to interact with the active conformation of ERa-LBD. Several phase-I metabolites retained the structural requirements for interacting with the pocket of ERa, thus pointing out a possible relevant xenoestrogenicity of cis-ZEN in vivo.…”

Section: Introductionmentioning

confidence: 99%