Advances in toxicity and transformation studies of zearalenone and its derivatives

Abstract

Abstract: Zearalenone (ZEN) is mycotoxin produced by the Fusarium fungi, which has various toxicity. Its own chemical structure and its derivatives are similar to estrogen. ZEN and its derivatives can lead to disturbance of estrogen balance and harm the reproductive system when ingested by animals or humans, change the cellular gene structure and thus affect the expression of various genes, damage the immune system of the organism and weaken the immune response. Zearalenone is transformed and metabolized into zearalenone derivatives during food processing and absorption by animals and plants, the toxicity of these derivatives is altered due to structural and physicochemical changes. The study of the toxicity of zearalenone and its derivatives as well as their transformation and metabolism in various organisms is important for food security and mycotoxin toxicity risk assessment.

Key words: Zearalenone, Zearalenone derivatives, Toxicity, Transformation, Mycotoxin

CLC Number:

TS201.6

Meng-Meng LI WANG RUIHU. Advances in toxicity and transformation studies of zearalenone and its derivatives[J]. FOOD SCIENCE, 0, (): 0-0.

References

[1]FINK-GREMMELS J, MALEKINEJAD H.Clinical effects and biochemical mechanisms associated with exposure to the mycoestrogen zearalenone[J].Animal Feed Science and Technology, 2007, 137(3-4):326-41
[2]BINDER S B, SCHWARTZ-ZIMMERMANN H E, VARGA E, et al.Metabolism of Zearalenone and Its Major Modified Forms in Pigs[J].Toxins (Basel), 2017, 9(2):-
[3]BAI X J, SUN C P, XU J, et al.Detoxification of zearalenone from corn oil by adsorption of functionalized GO systems[J]., 2018, :198-207
[4]CHAIN E P O C I T F, KNUTSEN H K, ALEXANDER J, et al.Risks for animal health related to the presence of zearalenone and its modified forms in feed[J].EFSA J, 2017, 15(7):-
[5]FREIRE L, SANT' ANA A S.Modified mycotoxins: An updated review on their formation, detection, occurrence, and toxic effects [J]., 2018, :189-205
[6]ALASSANE-KPEMBI I, KOLF-CLAUW M, GAUTHIER T, et al.New insights into mycotoxin mixtures: the toxicity of low doses of Type B trichothecenes on intestinal epithelial cells is synergistic[J].Toxicol Appl Pharmacol, 2013, 272(1):191-8
[7]BRODEHL A, MOLLER A, KUNTE H J, et al.Biotransformation of the mycotoxin zearalenone by fungi of the genera Rhizopus and Aspergillus[J].FEMS Microbiol Lett, 2014, 359(1):124-30
[8]食品安全国家标准食品中真菌毒素限量: [S].2017:
[9]BORZEKOWSKI A, DREWITZ T, KELLER J, et al.Biosynthesis and Characterization of Zearalenone-14-Sulfate, Zearalenone-14-Glucoside and Zearalenone-16-Glucoside Using Common Fungal Strains[J].Toxins (Basel), 2018, 10(3):-
[10]TIAN Y, TAN Y, YAN Z, et al.Antagonistic and Detoxification Potentials of Trichoderma Isolates for Control of Zearalenone (ZEN) Producing Fusarium graminearum[J]., 2017, 8(2710):-
[11]WARTH B, SULYOK M, BERTHILLER F, et al.New insights into the human metabolism of the Fusarium mycotoxins deoxynivalenol and zearalenone[J].Toxicol Lett, 2013, 220(1):88-94
[12]BELHASSEN H, JIMENEZ-DIAZ I, GHALI R, et al.Validation of a UHPLC-MS/MS method for quantification of zearalenone, alpha-zearalenol, beta-zearalenol, alpha-zearalanol, beta-zearalanol and zearalanone in human urine[J]., 2014, 962:68-74
[13]DE BOEVRE M, DI MAVUNGU J D, MAENE P, et al.Development and validation of an LC-MSMS method for the simultaneous determination of deoxynivalenol,zearalenone,T-2-toxin and some masked metabolites in different cereals and cereal-derived food[J].Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2012, 29(5):819-35
[14]STOEV S D.Foodborne mycotoxicoses,risk assessment and underestimated hazard of masked mycotoxins and joint mycotoxin effects or interaction[J].Environ Toxicol Pharmacol, 2015, 39(2):794-809
[15]ZHENG W, FENG N, WANG Y, et al.Effects of zearalenone and its derivatives on the synthesis and secretion of mammalian sex steroid hormones: A review [J].Food Chem Toxicol, 2019, 126:76-262
[16]FRIZZELL C, NDOSSI D, VERHAEGEN S, et al.Endocrine disrupting effects of zearalenone,alpha- and beta-zearalenol at the level of nuclear receptor binding and steroidogenesis[J].Toxicol Lett, 2011, 206(2):210-7
[17]YANG H, CHUNG D H, KIM Y B, et al.Ribotoxic mycotoxin deoxynivalenol induces G2M cell cycle arrest via p21CipWAF1 mRNA stabilization in human epithelial cells[J].Toxicology, 2008, 243(1-2):145-54
[18]TIEMANN U, VIERGUTZ T, JONAS L, et al.Influence of the mycotoxins alpha- and beta-zearalenol and deoxynivalenol on the cell cycle of cultured porcine endometrial cells[J].Reprod Toxicol, 2003, 17(2):209-18
[19]KIANG D T, KENNEDY B J, PATHRE S V, et al.Binding characteristics of zearalenone analogs to estrogen receptors[J].Cancer Res, 1978, 38(11 Pt 1):3611-5
[20]TATAY E, ESPIN S, GARCIA-FERNANDEZ A J, et al.Estrogenic activity of zearalenone,alpha-zearalenol and beta-zearalenol assessed using the E-screen assay in MCF-7 cells[J].Toxicol Mech Methods, 2018, 28(4):239-42
[21]EZE U A, HUNTRISS J, ROUTLEDGE M N, et al.The effect of individual and mixtures of mycotoxins and persistent organochloride pesticides on oestrogen receptor transcriptional activation using in vitro reporter gene assays[J]., 2019, 130(68):78-
[22]DRZYMALA S S, BINDER J, BRODEHL A, et al.Estrogenicity of novel phase I and phase II metabolites of zearalenone and cis-zearalenone[J]., 2015, 105(2):10-
[23]FRIZZELL C, UHLIG S, MILES C O, et al.Biotransformation of zearalenone and zearalenols to their major glucuronide metabolites reduces estrogenic activity[J].Toxicol In Vitro, 2015, 29(3):575-81
[24].Appropriateness to set a group health‐based guidance value for zearalenone and its modified forms[J]., 2016, 14(4):-
[25]KHAN S N, KHAN A U.Role of histone acetylation in cell physiology and diseases: An update[J].Clin Chim Acta, 2010, 411(19-20):1401-11
[26]FLECK S C, HILDEBRAND A A, PFEIFFER E, et al.Catechol metabolites of zeranol and 17beta-estradiol: a comparative in vitro study on the induction of oxidative DNA damage and methylation by catechol-O-methyltransferase[J].Toxicol Lett, 2012, 210(1):9-14
[27]AYED Y, AYED-BOUSSEMA I, OUANES Z, et al.In vitro and in vivo induction of chromosome aberrations by alpha- and beta-zearalenols: comparison with zearalenone[J].Mutat Res, 2011, 726(1):42-6
[28]MARIN D E, PISTOL G C, BULGARU C V, et al.Cytotoxic and inflammatory effects of individual and combined exposure of HepG2 cells to zearalenone and its metabolites[J].Naunyn Schmiedebergs Arch Pharmacol, 2019, 392(8):937-47
[29]BEN SALEM I, PROLA A, BOUSSABBEH M, et al.Activation of ER stress and apoptosis by alpha- and beta-zearalenol in HCT116 cells, protective role of Quercetin[J]., 2016, 53:42-334
[30]LUONGO D, SEVERINO L, BERGAMO P, et al.Interactive effects of fumonisin B1 and alpha-zearalenol on proliferation and cytokine expression in Jurkat T cells[J].Toxicol In Vitro, 2006, 20(8):1403-10
[31]MARIN D E, TARANU I, BURLACU R, et al.Effects of zearalenone and its derivatives on the innate immune response of swine[J].Toxicon, 2010, 56(6):956-63
[32]MARIN D E, TARANU I, BURLACU R, et al.Effects of zearalenone and its derivatives on porcine immune response[J].Toxicol In Vitro, 2011, 25(8):1981-8
[33]SANG Y, LI W, ZHANG G.The protective effect of resveratrol against cytotoxicity induced by mycotoxin,zearalenone[J].Food Funct, 2016, 7(9):3703-15
[34]TATAY E, ESPIN S, GARCIA-FERNANDEZ A J, et al.Oxidative damage and disturbance of antioxidant capacity by zearalenone and its metabolites in human cells[J].Toxicol In Vitro, 2017, 45(Pt 3):334-9
[35]BEN SALAH-ABBES J, BELGACEM H, EZZDINI K, et al.Zearalenone nephrotoxicity: DNA fragmentation, apoptotic gene expression and oxidative stress protected by Lactobacillus plantarum MON03[J]., 2020, 175:28-35
[36]ABID-ESSEFI S, BOUAZIZ C, GOLLI-BENNOUR E E, et al.Comparative study of toxic effects of zearalenone and its two major metabolites alpha-zearalenol and beta-zearalenol on cultured human Caco-2 cells[J].J Biochem Mol Toxicol, 2009, 23(4):233-43
[37]BOUAZIZ C, SHARAF EL DEIN O, EL GOLLI E, et al.Different apoptotic pathways induced by zearalenone,T-2 toxin and ochratoxin A in human hepatoma cells[J].Toxicology, 2008, 254(1-2):19-28
[38]AGAHI F, FONT G, JUAN C, et al.Individual and Combined Effect of Zearalenone Derivates and Beauvericin Mycotoxins on SH-SY5Y Cells[J]., 2020, 12(4):-
[39]LU J, YU J Y, LIM S S, et al.Cellular mechanisms of the cytotoxic effects of the zearalenone metabolites alpha-zearalenol and beta-zearalenol on RAW2647 macrophages[J].Toxicol In Vitro, 2013, 27(3):1007-17
[40]CIRLINI M, BARILLI A, GALAVERNA G, et al.Study on the uptake and deglycosylation of the masked forms of zearalenone in human intestinal Caco-2 cells[J].Food Chem Toxicol, 2016, 98(Pt B):232-9
[41]DELLAFIORA L, PEROTTI A, GALAVERNA G, et al.On the masked mycotoxin zearalenone-14-glucoside. Does the mask truly hide?[J]., 2016, 111:42-139
[42]KARAMAN E F, ZEYBEL M, OZDEN S.Evaluation of the epigenetic alterations and gene expression levels of HepG2 cells exposed to zearalenone and alpha-zearalenol[J]., 2020, 326:52-60
[43]TATAY E, MECA G, FONT G, et al.Cytotoxic and interactive effects of zearalenone, α-zearalenol and β-zearalenol and formation of metabolites in HepG2 cells[J].Revista de Toxicologia, 2015, 31:95-187
[44]KOVALSKY P, KOS G, NAHRER K, et al.Co-Occurrence of Regulated, Masked and Emerging Mycotoxins and Secondary Metabolites in Finished Feed and Maize-An Extensive Survey[J]., 2016, 8(12):-
[45]DEMAEGDT H, DAMINET B, EVRARD A, et al.Endocrine activity of mycotoxins and mycotoxin mixtures[J]., 2016, 96:16-107
[46]EZE U A, HUNTRISS J D, ROUTLEDGE M N, et al.In vitro effects of single and binary mixtures of regulated mycotoxins and persistent organochloride pesticides on steroid hormone production in MA-10 Leydig cell line[J]., 2019, 60(80):272-
[47]PFEIFFER E, WEFERS D, HILDEBRAND A A, et al.Catechol metabolites of the mycotoxin zearalenone are poor substrates but potent inhibitors of catechol-O-methyltransferase[J].Mycotoxin Res, 2013, 29(3):177-83
[48]SECKY L, SVOBODA M, KLAMETH L, et al.The sulfatase pathway for estrogen formation: targets for the treatment and diagnosis of hormone-associated tumors[J]., 2013, :-
[49]COZZINI P, DELLAFIORA L.In silico approach to evaluate molecular interaction between mycotoxins and the estrogen receptors ligand binding domain: a case study on zearalenone and its metabolites[J].Toxicol Lett, 2012, 214(1):81-5
[50]AGAHI F, JUAN C, FONT G, et al.In silico methods for metabolomic and toxicity prediction of zearalenone, alpha-zearalenone and beta-zearalenone[J]., 2020, 146:-
[51]HE Y, YIN X, DONG J, et al.Transcriptome Analysis of Caco-2 Cells upon the Exposure of Mycotoxin Deoxynivalenol and Its Acetylated Derivatives[J]., 2021, 13(2):-
[52]HASAN M, BHUIYA N, HOSSAIN M.In silico molecular docking,PASS prediction and ADMET analysis for finding novel COX-2 inhibitor from Heliotropium indicum[J].Journal of Complementary Medicine Research, 2019, 10(3):142-
[53]DELLAFIORA L, RUOTOLO R, PEROTTI A, et al.Molecular insights on xenoestrogenic potential of zearalenone-14-glucoside through a mixed in vitroin silico approach[J].Food Chem Toxicol, 2017, 108(Pt A):257-66
[54]CHAIN E P O C I T F, KNUTSEN H K, BARREGARD L, et al.Appropriateness to set a group health-based guidance value for fumonisins and their modified forms[J].EFSA J, 2018, 16(2):e05172-
[55]STEINKELLNER H, BINAGLIA M, DALL' ASTA C, et al.Combined hazard assessment of mycotoxins and their modified forms applying relative potency factors: Zearalenone and T2/HT2 toxin[J]., 2019, 131:-
[56]BRYLA M, KSIENIEWICZ-WOZNIAK E, WASKIEWICZ A, et al.Transformations of Selected Fusarium Toxins and Their Modified Forms During Malt Loaf Production[J]., 2020, 12(6):-
[57]CHILAKA C A, DE BOEVRE M, ATANDA O O, et al.Fate of Fusarium mycotoxins during processing of Nigerian traditional infant foods (ogi and soybean powder)[J]., 2019, 116:18-408
[58]BERTHILLER F, CREWS C, DALL' ASTA C, et al.Masked mycotoxins: a review[J].Mol Nutr Food Res, 2013, 57(1):165-86
[59]ZINEDINE A, SORIANO J M, MOLTO J C, et al.Review on the toxicity,occurrence,metabolism,detoxification,regulations and intake of zearalenone: an oestrogenic mycotoxin[J].Food Chem Toxicol, 2007, 45(1):1-18
[60]RICHARDSON K E, HAGLER W M, MIROCHA C J.Production of zearalenone,alpha.- and .beta.-zearalenol,and .alpha.- and .beta.-zearalanol by Fusarium spp. in rice culture[J].Journal of Agricultural and Food Chemistry, 2002, 33(5):862-6
[61]ROGOWSKA A, POMASTOWSKI P, SAGANDYKOVA G, et al.Zearalenone and its metabolites: Effect on human health, metabolism and neutralisation methods[J]., 2019, 162:46-56
[62]BOSWALD C, ENGELHARDT G, VOGEL H, et al.Metabolism of the Fusarium mycotoxins zearalenone and deoxynivalenol by yeast strains of technological relevance[J].Nat Toxins, 1995, 3(3):138-44
[63]CHANG X, LIU H, SUN J, et al.Zearalenone Removal from Corn Oil by an Enzymatic Strategy[J]., 2020, 12(2):-
[64]RAI A, DAS M, TRIPATHI A.Occurrence and toxicity of a fusarium mycotoxin,zearalenone[J].Crit Rev Food Sci Nutr, 2020, 60(16):2710-29
[65]KIESSLING K H, PETTERSSON H, SANDHOLM K, et al.Metabolism of aflatoxin,ochratoxin,zearalenone,and three trichothecenes by intact rumen fluid,rumen protozoa,and rumen bacteria[J].Appl Environ Microbiol, 1984, 47(5):1070-3
[66]KENNEDY D G, HEWITT S A, MCEVOY J D, et al.Zeranol is formed from Fusarium spptoxins in cattle in vivo[J].Food Addit Contam, 1998, 15(4):393-400
[67]DALL' ERTA A, CIRLINI M, DALL' ASTA M, et al.Masked mycotoxins are efficiently hydrolyzed by human colonic microbiota releasing their aglycones[J].Chem Res Toxicol, 2013, 26(3):305-12
[68]GRATZ S W.Do Plant-Bound Masked Mycotoxins Contribute to Toxicity?[J]., 2017, 9(3):-
[69]GRATZ S W, DINESH R, YOSHINARI T, et al.Masked trichothecene and zearalenone mycotoxins withstand digestion and absorption in the upper GI tract but are efficiently hydrolyzed by human gut microbiota in vitro[J]., 2017, 61(4):-
[70]YANG S, ZHANG H, ZHANG J, et al.Deglucosylation of zearalenone-14-glucoside in animals and human liver leads to underestimation of exposure to zearalenone in humans[J].Arch Toxicol, 2018, 92(9):2779-91
[71]DELLAFIORA L, GALAVERNA G, RIGHI F, et al.Assessing the hydrolytic fate of the masked mycotoxin zearalenone-14-glucoside - A warning light for the need to look at the " maskedome"[J]., 2017, 99:9-16
[72]D’MELLO J P F, PLACINTA C M, MACDONALD A M C.Fusarium mycotoxins: a review of global implications for animal health,welfare and productivity[J].Animal Feed Science and Technology, 1999, 80(3-4):183-205
[73]MINERVINI F, GIANNOCCARO A, FORNELLI F, et al.Influence of mycotoxin zearalenone and its derivatives (alpha and beta zearalenol) on apoptosis and proliferation of cultured granulosa cells from equine ovaries[J]., 2006, 4:62-
[74]MALEKINEJAD H, MAAS-BAKKER R, FINK-GREMMELS J.Species differences in the hepatic biotransformation of zearalenone[J].Vet J, 2006, 172(1):96-102
[75]MIROCHA C J, PATHRE S V, ROBISON T S.Comparative metabolism of zearalenone and transmission into bovine milk[J]., 1981, 19:25-30
[76]VER?ILOVSKIS A, GEYS J, HUYBRECHTS B, et al.Simultaneous determination of masked forms of deoxynivalenol and zearalenone after oral dosing in rats by LC-MSMS[J].World Mycotoxin Journal, 2012, 5(3):303-18
[77]CATTEUW A, BROEKAERT N, DE BAERE S, et al.Insights into In Vivo Absolute Oral Bioavailability,Biotransformation,and Toxicokinetics of Zearalenone,alpha-Zearalenol,beta-Zearalenol,Zearalenone-14-glucoside,and Zearalenone-14-sulfate in Pigs[J].J Agric Food Chem, 2019, 67(12):3448-58
[78]YANG S, LI Y, DE BOEVRE M, et al.Toxicokinetics of alpha-zearalenol and its masked form in rats and the comparative biotransformation in liver microsomes from different livestock and humans[J]., 2020, 393:-
[79]COLEMAN J, BLAKE-KALFF M, DAVIES E.Detoxification of xenobiotics by plants: chemical modification and vacuolar compartmentation[J].Trends in Plant Science, 1997, 2(4):144-51
[80]BROEKAERT N, DEVREESE M, DE BAERE S, et al.Modified Fusarium mycotoxins unmasked: From occurrence in cereals to animal and human excretion[J]., 2015, 80:17-31
[81]MICHLMAYR H, VARGA E, LUPI F, et al.Synthesis of Mono- and Di-Glucosides of Zearalenone and alpha-/beta-Zearalenol by Recombinant Barley Glucosyltransferase HvUGT14077[J]., 2017, 9(2):-
[82]BRYLA M, WASKIEWICZ A, KSIENIEWICZ-WOZNIAK E, et al.Modified Fusarium Mycotoxins in Cereals and Their Products-Metabolism, Occurrence, and Toxicity: An Updated Review[J]., 2018, 23(4):-
[83]BERTHILLER F, LEMMENS M, WERNER U, et al.Short review: Metabolism of theFusarium mycotoxins deoxynivalenol and zearalenone in plants[J].Mycotoxin Res, 2007, 23(2):68-72
[84]KOHN B N, BUNZEL M.Zearalenone‐malonyl‐glucosides as phase II metabolites in plant cell suspension cultures[J].Cereal Chemistry, 2020, 98(1):175-82
[85]SANDERMANN H, JR.Plant metabolism of xenobiotics[J].Trends Biochem Sci, 1992, 17(2):82-4