Toxic effects of zearalenone and its derivatives α-zearalenol on male reproductive system in mice

Yang, Jian Ying; Wang, Guo Xin; Liu, Jia Li; Fan, Jing; Cui, Sheng

doi:10.1016/j.reprotox.2007.05.009

Cited by 83 publications

(39 citation statements)

References 41 publications

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“…ERα activation/interactions has been evident at picomolar or nanomolar concentrations using tests covering different steps of the estrogenic response: binding affinity (Takemura et al, 2007), activation of transcriptional activation (Frizzell et al, 2011), proliferation of MCF7 cells (Molina-Molina et al, 2014;Shier et al, 2001) and yeast transfected with ERα (Bovee et al, 2004), as well as results on transcriptional activation (ERα CALUX ® ) and receptor-ligand translocation (ERα redistribution assay), as obtained in this study. Active concentrations (pico to nanomolar range: this study, and studies aforementioned) were found to be much lower than the levels required to alter steroid metabolism (micromolar range, for examples see: (Frizzell et al, 2011;Gracia et al, 2007;Kolle et al, 2012;Ranzenigo et al, 2008;Yang et al, 2007). Interestingly, estrogen may stimulate activities of enzymes of steroidogenesis such as aromatase via ER-mediated regulation (Lee et al, 2012).…”

Section: Tab 2: Computed Results Of Zen and Reduced Derivativesmentioning

confidence: 59%

“…It has been well established that ZEN and metabolites activate estrogen receptors α and β (Bovee et al, 2004;Bravin et al, 2009;EFSA, 2011;Frizzell et al, 2011;Shier et al, 2001;Takemura et al, 2007;WHO, 2000). It has also been suggested that these molecules may alter steroidogenesis (Frizzell et al, 2011;Gracia et al, 2007;Kolle et al, 2012;Ranzenigo et al, 2008;Yang et al, 2007) and may act as an antagonist of the androgenic receptor (Molina-Molina et al, 2014). Undoubtedly, ZEN and metabolites might perturbate several toxicological pathways, but based on the body of available data and reviews from regulatory agencies, the critical effects are thought to result from estrogenic activity mainly through an activation of ERα (EFSA, 2011;Kuiper et al, 1997;WHO, 2000).…”

Section: Tab 2: Computed Results Of Zen and Reduced Derivativesmentioning

confidence: 99%

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Hazard assessment through hybrid in vitro / in silico approach: The case of zearalenone

Ehrlich

2015

ALTEX

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SummaryWithin the framework of reduction, refinement and replacement of animal experiments, new approaches for identification and characterization of chemical hazards have been developed. Grouping and read-across has been promoted as a most promising alternative approach. It uses existing toxicological information on a group of chemicals to make predictions on the toxicity of uncharacterized ones. In the present work, the feasibility of applying in vitro and in silico techniques to group chemicals for read-across was studied using the food mycotoxin zearalenone (ZEN) and metabolites as a case study. ZEN and its reduced metabolites are known to act through activation of the estrogen receptor α (ERα). The ranking of their estrogenic potencies appeared highly conserved across test systems including binding, in vitro and in vivo assays. This data suggests that activation of ERα may play a role in the molecular initiating event (MIE) and be predictive of adverse effects, and it provides the rationale to model receptor-binding for hazard identification. The investigation of receptor-ligand interactions through docking simulation proved to accurately rank estrogenic potencies of ZEN and reduced metabolites, showing the suitability of the model to address estrogenic potency for this group of compounds. Therefore, the model was further applied to biologically uncharacterized, commercially unavailable, oxidized ZEN metabolites (6α-, 6β-, 8α-, 8β-, 13-and 15-OH-ZEN). Except for 15-OH-ZEN, the data indicate that in general, the oxidized metabolites would be considered of lower estrogenic concern than ZEN and reduced metabolites.

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Section: Tab 2: Computed Results Of Zen and Reduced Derivativesmentioning

confidence: 59%

Section: Tab 2: Computed Results Of Zen and Reduced Derivativesmentioning

confidence: 99%

Hazard assessment through hybrid in vitro / in silico approach: The case of zearalenone

Ehrlich

2015

ALTEX

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“…The suspension was stirred; one drop was placed in a hemocytometer. At least 10 microscopic fields were observed at 400x magnification using a standard optical microscope and the percentage of motile sperm was determined [17] . The sperm morphology was assessed by smearing the sperm suspension (in 20 µL saline solution) onto a glass slide.…”

Section: Evaluation Of Sperm Motility and Morphologymentioning

confidence: 99%

“…Once air-dried, the cells were fixed in 96% ethanol for 5 min, stained with 0.5% gentian violet and rinsed with distilled water. A minimum of 600 spermatozoa were examined from each sample under a light microscope [17] .…”

Section: Evaluation Of Sperm Motility and Morphologymentioning

confidence: 99%

Reproductive Toxicology of Tartrazine (FD and C Yellow No. 5) in Swiss Albino Mice

Mehedi¹,

Ainad-Tabet²,

Mokrane³

et al. 2009

American J. of Pharmacology and Toxicology

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Abstract. Problem statement: Tartrazine (FD and C Yellow No. 5) is an orange-colored widely used in food products, drugs and cosmetics. This color has a potential toxicological risk. The current study evaluated the effect of sub-chronic consumption of tartrazine on the male reproductive system. Approach: Tartrazine was administered to adult male mice in drinking water at doses of 0, 0.1, 1 and 2.5% for 13 weeks. After that period, the weights of testes, epididymides and seminal vesicles were determined. Sperm counts in the testis and epididymides, motility, morphology and testis histology were assessed. Results: Body weight gain, absolute and relative testis, epididymis and seminal vesicles weights did not change. However, sperm count was decreased and sperm abnormalities were increased in the 2.5% tartrazine treated groups compared to the control. Sperm motility and histological changes in testis were observed in the middle and high treated groups. Conclusion/Recommendations: We concluded that excessive tartrazine consumption can have adverse effects on the male reproductive function. We suggested conducting surveys among the population to estimate their daily intake.

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“…injection at doses of 25-75 mg kg −1 body weight affects spermatogenesis and sperm quality by an unknown mechanism (Yang et al, 2007), while a single i.p. dose of ZEN (5 mg kg −1 ) induces testicular germ cell apoptosis in rats (Kim et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of zearalenone and α‐zearalenol toxicity on boar sperm DNA integrity

Tsakmakidis

Lymberopoulos

Khalifa

et al. 2008

J of Applied Toxicology

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This study aimed at investigating the in vitro effects of zearalenone (zen) and alpha-zearalenol (alpha-zen) on motility and nuclear chromatin integrity (NCI) of boar spermatozoa. Mycotoxins were tested, at levels ranging from 10 to 30 microg ml(-1) of diluted semen. Four boars were used for semen collection (eight replicates per boar, four per mycotoxin). After the addition of zen or alpha-zen, semen samples were incubated for 4 h at 38.5 degrees C, 5% CO(2) and 96% humidified air. Motility and NCI were assessed at 0 and 4 h of incubation. No significant differences were noticed in motility among the experimental groups (P > 0.05) for all tested boars. Chromatin instability was significantly higher (P < 0.05) in spermatozoa of only one boar treated with zen and alpha-zen independently of the dose. In conclusion, under our experimental conditions, zen and alpha-zen did not affect the motility of boar sperm, whereas the effects of these toxins on sperm NCI were individual-dependent.

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Toxic effects of zearalenone and its derivatives α-zearalenol on male reproductive system in mice

Cited by 83 publications

References 41 publications

Hazard assessment through hybrid in vitro / in silico approach: The case of zearalenone

Hazard assessment through hybrid in vitro / in silico approach: The case of zearalenone

Reproductive Toxicology of Tartrazine (FD and C Yellow No. 5) in Swiss Albino Mice

Evaluation of zearalenone and α‐zearalenol toxicity on boar sperm DNA integrity

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