Zearalenoneのソースを表示

{{chembox
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| ImageFile = Zearalenone.svg
| ImageSize =
| ImageFile1 = Zearalenone-from-xtal-3D-bs-17.png
| PIN = (3''S'',11''E'')-14,16-Dihydroxy-3-methyl-3,4,5,6,9,10-hexahydro-1''H''-2-benzoxacyclotetradecine-1,7(8''H'')-dione
| OtherNames = Mycotoxin F2
| Section1 = {{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4444897
| InChI = 1/C18H22O5/c1-12-6-5-9-14(19)8-4-2-3-7-13-10-15(20)11-16(21)17(13)18(22)23-12/h3,7,10-12,20-21H,2,4-6,8-9H2,1H3/b7-3+/t12-/m0/s1
| InChIKey = MBMQEIFVQACCCH-QBODLPLBBS
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| StdInChI = 1S/C18H22O5/c1-12-6-5-9-14(19)8-4-2-3-7-13-10-15(20)11-16(21)17(13)18(22)23-12/h3,7,10-12,20-21H,2,4-6,8-9H2,1H3/b7-3+/t12-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MBMQEIFVQACCCH-QBODLPLBSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 17924-92-4
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 5W827M159J
| PubChem = 5281576
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 454173
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C09981
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 10106
| SMILES = C[C@H]1CCCC(=O)CCC/C=C/c2cc(cc(c2C(=O)O1)O)O
}}
| Section2 = {{Chembox Properties
| C=18|H=22|O=5
| Appearance =
| Density =
| MeltingPt =
| BoilingPt =
| Solubility =
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| Section3 = {{Chembox Hazards
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'''Zearalenone''' ('''ZEN'''), also known as RAL and F-2 [[mycotoxin]], is a potent [[estrogenic]] [[metabolite]] produced by some ''[[Fusarium]]'' and ''[[Gibberella]]'' species.<ref name="Fermentek2">{{cite web|title=Zearalenone|date=January 2002 |url=http://www.fermentek.com/zearalenone|publisher=[[Fermentek]]}}</ref> Specifically, the ''[[Gibberella zeae]]'', the fungal species where zearalenone was initially detected, in its asexual/[[anamorph]] stage is known as ''Fusarium graminearum.''<ref>{{cite journal | vauthors = Liu J, Applegate T | title = Zearalenone (ZEN) in Livestock and Poultry: Dose, Toxicokinetics, Toxicity and Estrogenicity | journal = Toxins | volume = 12 | issue = 6 | pages = 377 | date = June 2020 | pmid = 32517357 | pmc = 7354539 | doi = 10.3390/toxins12060377 | doi-access = free }}</ref> Several ''Fusarium'' species produce toxic substances of considerable concern to livestock and poultry producers, namely [[deoxynivalenol]], [[T-2 toxin]], [[HT-2 toxin]], [[diacetoxyscirpenol]] (DAS) and zearalenone. Particularly, ZEN is produced by ''[[Fusarium graminearum]]'', ''[[Fusarium culmorum]]'', ''[[Fusarium cerealis]]'', ''[[Fusarium equiseti]]'',<ref name=":3">{{cite journal | vauthors = Bulgaru CV, Marin DE, Pistol GC, Taranu I | title = Zearalenone and the Immune Response | journal = Toxins | volume = 13 | issue = 4 | pages = 248 | date = March 2021 | pmid = 33807171 | doi = 10.3390/toxins13040248 | pmc = 8066068 | doi-access = free }}</ref> ''[[Fusarium verticillioides]]'',<ref name=":0">{{cite journal | vauthors = Ropejko K, Twarużek M | title = Zearalenone and Its Metabolites-General Overview, Occurrence, and Toxicity | journal = Toxins | volume = 13 | issue = 1 | pages = 35 | date = January 2021 | pmid = 33418872 | doi = 10.3390/toxins13010035 | pmc = 7825134 | doi-access = free }}</ref> and ''[[Fusarium incarnatum]]''.  Zearalenone is the primary toxin that binds to [[estrogen receptor]]s, causing [[infertility]], [[abortion]] or other breeding problems, especially in swine.<ref name=":0" /> Often, ZEN is detected together with deoxynivalenol in contaminated samples and its toxicity needs to be considered in combination with the presence of other toxins.<ref>{{cite journal | vauthors = Peillod C, Laborde M, Travel A, Mika A, Bailly JD, Cleva D, Boissieu C, Le Guennec J, Albaric O, Labrut S, Froment P, Tardieu D, Guerre P | display-authors = 6 | title = Toxic Effects of Fumonisins, Deoxynivalenol and Zearalenone Alone and in Combination in Ducks Fed the Maximum EUTolerated Level | journal = Toxins | volume = 13 | issue = 2 | pages = 152 | date = February 2021 | pmid = 33669302 | pmc = 7920068 | doi = 10.3390/toxins13020152 | doi-access = free }}</ref>

Zearalenone is heat-stable and is found worldwide in a number of cereal crops, such as [[maize]], [[barley]], [[oats]], [[wheat]], [[rice]], and [[sorghum]].<ref>{{cite journal | vauthors = Kuiper-Goodman T, Scott PM, Watanabe H | title = Risk assessment of the mycotoxin zearalenone | journal = Regulatory Toxicology and Pharmacology | volume = 7 | issue = 3 | pages = 253–306 | date = September 1987 | pmid = 2961013 | doi = 10.1016/0273-2300(87)90037-7 }}</ref><ref>{{cite journal| vauthors = Tanaka T, Hasegawa A, Yamamoto S, Lee US, Sugiura Y, Ueno Y |year=1988|title=Worldwide Contamination of Cereals by the ''Fusarium'' Mycotoxins Nivalenol, Deoxynivalenol, and Zearalenone. 1. Survey of 19 Countries|journal=Journal of Agricultural and Food Chemistry|publisher=American Chemical Society|volume=36|issue=5|pages=979–983|doi=10.1021/jf00083a019|bibcode=1988JAFC...36..979T }}</ref><ref name="ProssnitzBarton20142">{{cite journal | vauthors = Prossnitz ER, Barton M | title = Estrogen biology: new insights into GPER function and clinical opportunities | journal = Molecular and Cellular Endocrinology | volume = 389 | issue = 1–2 | pages = 71–83 | date = May 2014 | pmid = 24530924 | pmc = 4040308 | doi = 10.1016/j.mce.2014.02.002 }}</ref> Its production increases when the climate is warm with air humidity at or above twenty percent. <ref name=":0" /> The environmental pH plays also a role in the toxin's production. When temperatures fall to 15<sup>o</sup>C, alkaline soils still support ZEN production.  At the preferred ''Fusarium'' temperature, which ranges between 25<sup>o</sup>C and 30<sup>o</sup>C, neutral pH results in the greatest toxin production. <ref name=":1">{{cite journal | vauthors = Mahato DK, Devi S, Pandhi S, Sharma B, Maurya KK, Mishra S, Dhawan K, Selvakumar R, Kamle M, Mishra AK, Kumar P | display-authors = 6 | title = Occurrence, Impact on Agriculture, Human Health, and Management Strategies of Zearalenone in Food and Feed: A Review | journal = Toxins | volume = 13 | issue = 2 | pages = 92 | date = January 2021 | pmid = 33530606 | doi = 10.3390/toxins13020092 | pmc = 7912641 | doi-access = free }}</ref>

In addition to its actions on the classical [[estrogen receptor]]s, zearalenone has been found to act as an [[agonist]] of the [[GPER]] (GPR30).<ref name="ProssnitzBarton20142"/>

==Chemical and physical properties==
Zearalenone is a white [[crystalline]] solid, with molecular formula C<sub>18</sub>H<sub>22</sub>O<sub>5</sub> and 318.364 g/mol molecular weight. It is a [[Resorcylic acid lactone|resorcyclic acid lactone]]. It exhibits blue-green [[fluorescence]] when excited by long wavelength [[Ultraviolet light|ultraviolet]] (UV) light (360&nbsp;nm) and a more intense green fluorescence when excited with short wavelength UV light (260&nbsp;nm).<ref name=":0" /> In methanol, UV absorption maxima occur at 236 (e = 29,700), 274 (e = 13,909) and 316&nbsp;nm (e = 6,020). Maximum fluorescence in [[ethanol]] occurs with irradiation at 314&nbsp;nm and with emission at 450&nbsp;nm. Solubility in water is about 0.002 g/100 mL. It is slightly soluble in [[hexane]] and progressively more so in [[benzene]], [[acetonitrile]], [[methylene chloride]], [[methanol]], [[ethanol]], and [[acetone]]. It is also soluble in aqueous [[alkali]].{{cn|date=October 2023}}

The naturally occurring [[Cis–trans isomerism|isomer]] ''trans''-zearalenone (trans-ZEN) is transformed by ultraviolet irradiation to ''cis''-zearalenone (cis-ZEN).<ref>{{cite journal | vauthors = Brezina U, Kersten S, Valenta H, Sperfeld P, Riedel J, Dänicke S | title = UV-induced cis-trans isomerization of zearalenone in contaminated maize | journal = Mycotoxin Research | volume = 29 | issue = 4 | pages = 221–227 | date = November 2013 | pmid = 24018604 | doi = 10.1007/s12550-013-0178-7 | s2cid = 17466231 }}</ref>

== Metabolic pathways and products ==
Zearalenone is metabolically transformed to α-zearalenol (α-Zel) or (α-Zol), β-zearalenol (β-Zel) or (β-Zol), α-zearalanol (α-Zal), β-zearalanol (β-Zal), and zearalanone (ZAN) in animals. <ref name=":1" /><ref name=":2">{{cite journal | vauthors = Yang D, Jiang X, Sun J, Li X, Li X, Jiao R, Peng Z, Li Y, Bai W | display-authors = 6 | title = Toxic effects of zearalenone on gametogenesis and embryonic development: A molecular point of review | journal = Food and Chemical Toxicology | volume = 119 | pages = 24–30 | date = September 2018 | pmid = 29864477 | doi = 10.1016/j.fct.2018.06.003 | s2cid = 46927149 }}</ref> The relative composition of these metabolic products varies by species.  In pigs, cows and ducks, α-Zel is the dominant form detected.<ref>{{cite journal | vauthors = Peillod C, Laborde M, Travel A, Mika A, Bailly JD, Cleva D, Boissieu C, Le Guennec J, Albaric O, Labrut S, Froment P, Tardieu D, Guerre P | display-authors = 6 | title = Toxic Effects of Fumonisins, Deoxynivalenol and Zearalenone Alone and in Combination in Ducks Fed the Maximum EUTolerated Level | journal = Toxins | volume = 13 | issue = 2 | pages = 152 | date = February 2021 | pmid = 33669302 | pmc = 7920068 | doi = 10.3390/toxins13020152 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Gruber-Dorninger C, Faas J, Doupovec B, Aleschko M, Stoiber C, Höbartner-Gußl A, Schöndorfer K, Killinger M, Zebeli Q, Schatzmayr D | display-authors = 6 | title = Metabolism of Zearalenone in the Rumen of Dairy Cows with and without Application of a Zearalenone-Degrading Enzyme | journal = Toxins | volume = 13 | issue = 2 | pages = 84 | date = January 2021 | pmid = 33499402 | pmc = 7911295 | doi = 10.3390/toxins13020084 | doi-access = free }}</ref><ref name=":0" /> In humans, both α-Zel and β-Zel are seen in urine samples, with the beta form being prevalent.<ref>{{cite journal | vauthors = Al-Jaal B, Latiff A, Salama S, Hussain HM, Al-Thani NA, Al-Naimi N, Al-Qasmi N, Horvatovich P, Jaganjac M | display-authors = 6 | title = Analysis of Multiple Mycotoxins in the Qatari Population and Their Relation to Markers of Oxidative Stress | journal = Toxins | volume = 13 | issue = 4 | pages = 267 | date = April 2021 | pmid = 33917988 | pmc = 8068385 | doi = 10.3390/toxins13040267 | doi-access = free }}</ref>  In chickens, β-Zel is the dominant form and in plant cells, the metabolic product zeralenonne-14-O-β-glucoside has been detected.<ref name=":0" /> Additionally, in the organs of animals these metabolic products are further modified to yield zearalenone-14-glucuronide (ZEN-14GlcA), α-zearalenol-glucuronide (α-Zel-14G) and  β-zearalenol-glucuronide (β-Zel-14G).<ref name=":4">{{cite journal | vauthors = Yan Z, Wang L, Wang J, Tan Y, Yu D, Chang X, Fan Y, Zhao D, Wang C, De Boevre M, De Saeger S, Sun C, Wu A | display-authors = 6 | title = A QuEChERS-Based Liquid Chromatography-Tandem Mass Spectrometry Method for the Simultaneous Determination of Nine Zearalenone-Like Mycotoxins in Pigs | journal = Toxins | volume = 10 | issue = 3 | pages = 129 | date = March 2018 | pmid = 29558416 | pmc = 5869417 | doi = 10.3390/toxins10030129 | doi-access = free }}</ref>

==Dermal exposure==
Zearalenone can permeate through the human skin.<ref>{{cite journal | vauthors = Boonen J, Malysheva SV, Taevernier L, Diana Di Mavungu J, De Saeger S, De Spiegeleer B | title = Human skin penetration of selected model mycotoxins | journal = Toxicology | volume = 301 | issue = 1–3 | pages = 21–32 | date = November 2012 | pmid = 22749975 | doi = 10.1016/j.tox.2012.06.012 | bibcode = 2012Toxgy.301...21B }}</ref> However, no significant hormonal effects are expected after dermal contact in normal agricultural or residential environments.

==Reproduction==
Zearalenone structure is similar to [[estrogen]]s and α-zearalenol binds with an even greater affinity estrogen receptors, while β-zearalenol's affinity is lower than both the parent compound's and α-Zel's binding affinity.<ref name=":0" /> This identifies ZEN and its metabolites as [[xenoestrogen]]s.<ref name=":3" /> The human and livestock exposure to ZEN through the diet poses health concern due to the onset of several [[Sexual dysfunction|sexual disorders]] and alterations in the development of [[sexual apparatus]].<ref>{{cite journal | vauthors = Massart F, Saggese G | title = Oestrogenic mycotoxin exposures and precocious pubertal development | journal = International Journal of Andrology | volume = 33 | issue = 2 | pages = 369–376 | date = April 2010 | pmid = 20002219 | doi = 10.1111/j.1365-2605.2009.01009.x | doi-access = free }}</ref><ref>{{cite journal | vauthors = Schoevers EJ, Santos RR, Colenbrander B, Fink-Gremmels J, Roelen BA | title = Transgenerational toxicity of Zearalenone in pigs | journal = Reproductive Toxicology | volume = 34 | issue = 1 | pages = 110–119 | date = August 2012 | pmid = 22484360 | doi = 10.1016/j.reprotox.2012.03.004 | bibcode = 2012RepTx..34..110S }}</ref> There are reliable case reports of early puberty in girls chronically exposed to ZEN in various regions of the world.<ref name="HuezaRaspantini20142">{{cite journal | vauthors = Hueza IM, Raspantini PC, Raspantini LE, Latorre AO, Górniak SL | title = Zearalenone, an estrogenic mycotoxin, is an immunotoxic compound | journal = Toxins | volume = 6 | issue = 3 | pages = 1080–1095 | date = March 2014 | pmid = 24632555 | pmc = 3968378 | doi = 10.3390/toxins6031080 | doi-access = free }}</ref> In mice, ZEN consumption was linked to a decline of potent sperm and egg cells, an increase to double-stranded breaks in DNA and activation of DNA repair mechanisms, followed by embryonic development challenges that reduced the viability of offspring.<ref name=":2" />

==Sampling and analysis==
In common with other mycotoxins, sampling food commodities for zearalenone must be carried out to obtain samples representative of the consignment under test. Commonly used extraction solvents are aqueous mixtures of methanol, [[acetonitrile]], or [[ethyl acetate]] followed by a range of different clean-up procedures that depend in part on the food and on the detection method in use. [[Thin-layer chromatography]] (TLC) methods and [[high-performance liquid chromatography]] (HPLC) are commonly used. The TLC method for zearalenone is: normal phase [[silica gel]] plates, the eluent: 90% [[dichloromethane]], 10% v/v acetone; or reverse phase C18 silica plates; the eluent: 90% v/v [[methanol]], 10% water. Zearalenone gives unmistakable blue luminiscence under UV.<ref name="Fermentek2" /> HPLC alone is not sufficient, as it may often yield false positive results. Today, HPLC-[[MS/MS]] analysis is used to quantify and confirm the presence of zearalenone.

Typically, the representative sample is commuted and homogenized then few grams are used for extraction with acetonitrile/water mixture. The procedure is the widely used [[QuEChERS]] method that quickly and effectively extracts small molecules, like mycotoxins and pesticides, from complex food matrices and animal tissues.  The determination step relies on [[Liquid chromatography–mass spectrometry|liquid chromatography - mass-spectrometry]] (LC-MS/MS).<ref name=":4" /> Another approach for the analysis of ZEA, without the requirement of expensive instrumentation, is developing specific [[Peptidomimetic|peptide mimetic]] with the [[Bioluminescence|bioluminescent]] ''Gaussia'' [[luciferase]] fused as one protein that can bind specifically to ZEA.<ref>{{cite journal | vauthors = Peltomaa R, Fikacek S, Benito-Peña E, Barderas R, Head T, Deo S, Daunert S, Moreno-Bondi MC | display-authors = 6 | title = Bioluminescent detection of zearalenone using recombinant peptidomimetic Gaussia luciferase fusion protein | journal = Mikrochimica Acta | volume = 187 | issue = 10 | pages = 547 | date = September 2020 | pmid = 32886242 | doi = 10.1007/s00604-020-04538-7 | pmc = 7938698 }}</ref>

== See also ==
* [[α-Zearalenol]]
* [[β-Zearalenol]]
* [[Taleranol]]
* [[Trichothecene]]
* [[Zeranol]]
* [[Zearalanone]]

== References ==
{{Reflist|30em}}

== External links ==
* {{Commonscatinline}}
* {{ cite web | url = http://www.inchem.org/documents/jecfa/jecmono/v44jec14.htm | vauthors = Eriksen GS, Pennington J, Schlatter J | work = WHO International Programme on Chemical Safety - Safety Evaluation of Certain Food Additives and Contaminants | title = Zearalenone | publisher = Inchem | id = WHO Food Additives Series | volume = 44 | year = 2000 }}

{{Toxins}}
{{Xenoestrogens}}
{{Estrogen receptor modulators}}

[[Category:Aromatase inhibitors]]
[[Category:Ecotoxicology]]
[[Category:Female reproductive toxins]]
[[Category:GPER modulators]]
[[Category:Heterocyclic compounds with 2 rings]]
[[Category:Mycoestrogens]]
[[Category:Mycotoxins]]
[[Category:Oxygen heterocycles]]
[[Category:Resorcinols]]
[[Category:Lactones]]
[[Category:Ketones]]