Zearalenone

Mutat Res. 2004 Jan 10;557(1):19-27.

Ochratoxin A and zearalenone: a comparative study on genotoxic effects and cell death induced in bovine lymphocytes.[Pubmed: 14706515]

Ochratoxin A (OTA) and Zearalenone (ZEA), two naturally occurring contaminants of animal feed, have been implicated in several mycotoxicoses in farm livestock but there is little information on their genotoxicity and toxicity in these species.
METHODS AND RESULTS:
Therefore, we investigated on the cytogenetic and cytotoxic effects of both OTA and ZEA in in vitro cultures of bovine lymphocytes. We determined chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) as well as the mitotic index (MI) and cell viability following OTA and ZEA treatment.
CONCLUSIONS:
This report is the first to provide evidence of a statistically significant increase of structural CAs and of SCEs/cell associated with a reduction of the MI in all OTA- and ZEA-treated bovine lymphocyte cultures and a clear reproducible reducing effect of OTA on cell viability mediated by enhanced apoptosis. OTA-induced programmed cell death was not limited to bovine lymphocytes, as comparable data were demonstrated in the human leukemic T-cell line Jurkat.

Front Pharmacol. 2019 Oct 18;10:1160.

Zearalenone and ß-Zearalenol But Not Their Glucosides Inhibit Heat Shock Protein 90 ATPase Activity.[Pubmed: 31680951 ]

The mycotoxin Zearalenone (ZEN) is produced by many plant pathogenic Fusarium species. It is well known for its estrogenic activity in humans and animals, but whether ZEN has a role in plant-pathogen interaction and which process it is targeting in planta was so far unclear.
METHODS AND RESULTS:
We found that treatment of Arabidopsis thaliana seedlings with ZEN induced transcription of the AtHSP90.1 gene. This heat shock protein (HSP) plays an important role in plant-pathogen interaction, assisting in stability and functionality of various disease resistance gene products. Inhibition of HSP90 ATPase activity impairs functionality. Because HSP90 inhibitors are known to induce HSP90 gene expression and due to the structural similarity with the known HSP90 inhibitor radicicol (RAD), we tested whether ZEN and its phase I metabolites α- and ß-zearalenol are also HSP90 ATPase inhibitors. Indeed, AtHSP90.1 and wheat TaHSP90-2 were inhibited by ZEN and ß-zearalenol, while α-zearalenol was almost inactive. Plants can efficiently glycosylate ZEN and α/ß-zearalenol. We therefore tested whether glucosylation has an effect on the inhibitory activity of these metabolites. Expression of the A. thaliana glucosyltransferase UGT73C6 conferred RAD resistance to a sensitive yeast strain. Glucosylation of RAD, ZEN, and α/ß-zearalenol abolished the in vitro inhibitory activity with recombinant HSP90 purified from Escherichia coli.
CONCLUSIONS:
In conclusion, the mycotoxin ZEN has a very prominent target in plants, HSP90, but it can be inactivated by glycosylation. This may explain why there is little evidence for a virulence function of ZEN in host plants.

Toxicology. 2008 Dec 5;254(1-2):19-28.

Different apoptotic pathways induced by zearalenone, T-2 toxin and ochratoxin A in human hepatoma cells.[Pubmed: 18834919 ]

Mycotoxins, secondary metabolites produced by moulds, have been shown to cause diverse toxic effects in animals and are also suspected of disease causation in humans.
METHODS AND RESULTS:
The present study compares the molecular mechanisms of the toxicity of Zearalenone (ZEN), T-2 toxin and ochratoxin A (OTA) in human hepatoma cells HepG2. The three mycotoxins-induced a caspase-dependent mitochondrial apoptotic pathway. The mitochondrial alterations include: bax relocalisation into the mitochondrial outer membrane, loss of the mitochondrial transmembrane potential, PTPC opening, and cytochrome c (but not AIF) release. In the presence of ZEN and T-2 toxin, reactive oxygen species (ROS) level was highly increased at an early stage even before mitochondrial alterations were observed, whereas OTA-induced only O(2)(-) generation among total ROS. This ROS production appears as a consequence of mitochondrial alterations. HepG2 cell treatment with the p53 inhibitor pifithrin-alpha (PFT) and western blot analysis suggested that both ZEN and OTA, but not T-2 toxin, trigger a p53-dependent apoptotic pathway.
CONCLUSIONS:
These results clearly point to a central role of mitochondria in the apoptotic process induced by ZEN, T-2 toxin and OTA and provide new insights into the molecular mechanisms by which these mycotoxins might promote hepatotoxicty.

Food Chem. 2020 Mar 1;307:125546.

Molecular reaction mechanism for elimination of zearalenone during simulated alkali neutralization process of corn oil.[Pubmed: 31639580]

Zearalenone (ZEN) is one of the most widely distributed harmful mycotoxins produced by Fusarium species, especially deposited in corn oil.
METHODS AND RESULTS:
In this study, we systematically tracked the changes of ZEN in the refining of corn oil, and especially during neutralization process. An alkali neutralization process could remove certain amounts of ZEN that was much more than that of others refining steps. In a mimicking condition, ZEN contents decreased continuously and significantly with increasing neutralization temperature. However, when returned to neutral, recoverable ZEN decreased with increasing temperature, which confirmed more degradation of ZEN at high temperature. HPLC-Q/TOF MS and NMR evidence showed that non-reversible hydrolyzate followed decarboxylation was observed in a high-temperature alkali neutralization condition.
CONCLUSIONS:
The results may serve as the scientific basis for the elimination of Zearalenone in refined vegetable oils, and provide clues to understanding the oil-safety aspects of elimination of Zearalenone.