Mycotoxins: Biotransformation and Bioavailability Assessment Using Caco-2 Cell Monolayer

. 2020 Sep 30 ; 12 (10) : . [epub] 20200930

Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články, práce podpořená grantem, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid33008111

Grantová podpora
INTER-COST LTC20015 Ministerstvo Školství, Mládeže a Tělovýchovy - International
NPU I (LO1601, MSMT-43760/2015) Czech National Program of Sustainability - International

The determination of mycotoxins content in food is not sufficient for the prediction of their potential in vivo cytotoxicity because it does not reflect their bioavailability and mutual interactions within complex matrices, which may significantly alter the toxic effects. Moreover, many mycotoxins undergo biotransformation and metabolization during the intestinal absorption process. Biotransformation is predominantly the conversion of mycotoxins meditated by cytochrome P450 and other enzymes. This should transform the toxins to nontoxic metabolites but it may possibly result in unexpectedly high toxicity. Therefore, the verification of biotransformation and bioavailability provides valuable information to correctly interpret occurrence data and biomonitoring results. Among all of the methods available, the in vitro models using monolayer formed by epithelial cells from the human colon (Caco-2 cell) have been extensively used for evaluating the permeability, bioavailability, intestinal transport, and metabolism of toxic and biologically active compounds. Here, the strengths and limitations of both in vivo and in vitro techniques used to determine bioavailability are reviewed, along with current detailed data about biotransformation of mycotoxins. Furthermore, the molecular mechanism of mycotoxin effects is also discussed regarding the disorder of intestinal barrier integrity induced by mycotoxins.

Zobrazit více v PubMed

De Boevre M., Graniczkowska K., Saeger S. De Metabolism of modified mycotoxins studied through in vitro and in vivo models: An overview. Toxicol. Lett. 2015;233:24–28. doi: 10.1016/j.toxlet.2014.12.011. PubMed DOI

Smith M.C., Gheux A., Coton M., Madec S., Hymery N., Coton E. In vitro co-culture models to evaluate acute cytotoxicity of individual and combined mycotoxin exposures on Caco-2, THP-1 and HepaRG human cell lines. Chem. Biol. Interact. 2018;281:51–59. doi: 10.1016/j.cbi.2017.12.004. PubMed DOI

Kebede H., Liu X., Jin J., Xing F. Current status of major mycotoxins contamination in food and feed in Africa. Food Control. 2020;110:106975. doi: 10.1016/j.foodcont.2019.106975. DOI

Fernández-Blanco C., Elmo L., Waldner T., Ruiz M.J. Cytotoxic effects induced by patulin, deoxynivalenol and toxin T2 individually and in combination in hepatic cells (HepG2) Food Chem. Toxicol. 2018;120:12–23. doi: 10.1016/j.fct.2018.06.019. PubMed DOI

Pankaj S.K., Shi H., Keener K.M. A review of novel physical and chemical decontamination technologies for aflatoxin in food. Trends Food Sci. Technol. 2018;71:73–83. doi: 10.1016/j.tifs.2017.11.007. DOI

Seyed Toutounchi N., Hogenkamp A., Varasteh S., van’t Land B., Garssen J., Kraneveld A.D., Folkerts G., Braber S. Fusarium Mycotoxins Disrupt the Barrier and Induce IL-6 Release in a Human Placental Epithelium Cell Line. Toxins. 2019;11:665. doi: 10.3390/toxins11110665. PubMed DOI PMC

Stanciu O., Loghin F., Filip L., Cozma A., Miere D., Mañes J., Banc R. Occurence of Fusarium Mycotoxins in Wheat from Europe—A Review. Acta Univ. Cibiniensis. Ser. E Food Technol. 2015;19:35–60. doi: 10.1515/aucft-2015-0005. DOI

Raghubeer S., Nagiah S., Chuturgoon A. Ochratoxin A upregulates biomarkers associated with hypoxia and transformation in human kidney cells. Toxicol. In Vitro. 2019;57:211–216. doi: 10.1016/j.tiv.2019.03.016. PubMed DOI

Hymery N., Mounier J., Coton E. Effect of Penicillium roqueforti mycotoxins on Caco-2 cells: Acute and chronic exposure. Toxicol. In Vitro. 2018;48:188–194. doi: 10.1016/j.tiv.2018.01.017. PubMed DOI

Assunção R., Ferreira M., Martins C., Diaz I., Padilla B., Dupont D., Bragança M., Alvito P. Applicability of in vitro methods to study patulin bioaccessibility and its effects on intestinal membrane integrity. J. Toxicol. Environ. Heal. Part A Curr. Issues. 2014;77:983–992. doi: 10.1080/15287394.2014.911138. PubMed DOI

Hussain S., Asi M.R., Iqbal M., Khalid N., Wajih-ul-Hassan S., Ariño A. Patulin Mycotoxin in Mango and Orange Fruits, Juices, Pulps, and Jams Marketed in Pakistan. Toxins. 2020;12:52. doi: 10.3390/toxins12010052. PubMed DOI PMC

Moss M.O. Risk assessment for aflatoxins in foodstuffs. Int. Biodeterior. Biodegrad. 2002;50:137–142. doi: 10.1016/S0964-8305(02)00078-1. DOI

Rushing B.R., Selim M.I. Aflatoxin B1: A review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods. Food Chem. Toxicol. 2019;124:81–100. doi: 10.1016/j.fct.2018.11.047. PubMed DOI

Rodríguez-Carrasco Y., Mañes J., Berrada H., Juan C. Development and validation of a LC-ESI-MS/MS method for the determination of alternaria toxins alternariol, alternariol methyl-ether and tentoxin in tomato and tomato-based products. Toxins. 2016;8:328. doi: 10.3390/toxins8110328. PubMed DOI PMC

Gotthardt M., Kanawati B., Schmidt F., Asam S., Hammerl R., Frank O., Hofmann T., Schmitt-Kopplin P., Rychlik M. Comprehensive Analysis of the Alternaria Mycobolome Using Mass Spectrometry Based Metabolomics. Mol. Nutr. Food Res. 2020;64:1900558. doi: 10.1002/mnfr.201900558. PubMed DOI

De Angelis E., Monaci L., Mackie A., Salt L., Visconti A. Reprint of “bioaccessibility of T-2 and HT-2 toxins in mycotoxin contaminated bread models submitted to in vitro human digestion”. Innov. Food Sci. Emerg. Technol. 2013;25:88–96. doi: 10.1016/j.ifset.2014.07.009. DOI

Ling A., Sun L., Guo W., Sun S., Yang J., Zhao Z. Individual and combined cytotoxic effects of T-2 toxin and its four metabolites on porcine Leydig cells. Food Chem. Toxicol. 2020;139:111277. doi: 10.1016/j.fct.2020.111277. PubMed DOI

Huang Z., Wang Y., Qiu M., Sun L., Liao J., Wang R., Sun X., Bi S., Gooneratne R. Effect of T-2 toxin-injected shrimp muscle extracts on mouse macrophage cells (RAW264.7) Drug Chem. Toxicol. 2018;41:16–21. doi: 10.1080/01480545.2016.1278227. PubMed DOI

Kang R., Perveen A., Li C. Effects of maternal T-2 toxin exposure on the hepatic glycolipid metabolism in young mice. Ecotoxicol. Environ. Saf. 2020;196:110530. doi: 10.1016/j.ecoenv.2020.110530. PubMed DOI

Kasimir M., Behrens M., Schulz M., Kuchenbuch H., Focke C., Humpf H.-U. Intestinal Metabolism of α- and β-Glucosylated Modified Mycotoxins T-2 and HT-2 Toxin in the Pig Cecum Model. J. Agric. Food Chem. 2020 doi: 10.1021/acs.jafc.0c00576. PubMed DOI

Schuhmacher-Wolz U., Heine K., Schneider K. Report on toxicity data on trichothecene mycotoxins HT-2 and T-2 toxins. EFSA Support. Publ. 2010;7 doi: 10.2903/sp.efsa.2010.EN-65. DOI

Zhou H., George S., Hay C., Lee J., Qian H., Sun X. Individual and combined effects of Aflatoxin B1, Deoxynivalenol and Zearalenone on HepG2 and RAW 264.7 cell lines. Food Chem. Toxicol. 2017;103:18–27. doi: 10.1016/j.fct.2017.02.017. PubMed DOI

Fernández-Blanco C., Font G., Ruiz M.J. Interaction effects of enniatin B, deoxinivalenol and alternariol in Caco-2 cells. Toxicol. Lett. 2016;241:38–48. doi: 10.1016/j.toxlet.2015.11.005. PubMed DOI

García G.R., Payros D., Pinton P., Dogi C.A., Laffitte J., Neves M., González Pereyra M.L., Cavaglieri L.R., Oswald I.P. Intestinal toxicity of deoxynivalenol is limited by Lactobacillus rhamnosus RC007 in pig jejunum explants. Arch. Toxicol. 2018;92:983–993. doi: 10.1007/s00204-017-2083-x. PubMed DOI

Pestka J.J. Mechanisms of deoxynivalenol-induced gene expression and apoptosis. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 2008;25:1128–1140. doi: 10.1080/02652030802056626. PubMed DOI PMC

Pestka J.J., Smolinski A.T. Deoxynivalenol: Toxicology and potential effects on humans. J. Toxicol. Environ. Heal. Part B Crit. Rev. 2005;8:39–69. doi: 10.1080/10937400590889458. PubMed DOI

Wang H.W., Wang J.Q., Zheng B.Q., Li S.L., Zhang Y.D., Li F.D., Zheng N. Cytotoxicity induced by ochratoxin A, zearalenone, and α-zearalenol: Effects of individual and combined treatment. Food Chem. Toxicol. 2014;71:217–224. doi: 10.1016/j.fct.2014.05.032. PubMed DOI

Yang D., Jiang X., Sun J., Li X., Li X., Jiao R., Peng Z., Li Y., Bai W. Toxic effects of zearalenone on gametogenesis and embryonic development: A molecular point of review. Food Chem. Toxicol. 2018;119:24–30. doi: 10.1016/j.fct.2018.06.003. PubMed DOI

Zinedine A., Soriano J.M., Moltó J.C., Mañes J. Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: An oestrogenic mycotoxin. Food Chem. Toxicol. 2007;45:1–18. doi: 10.1016/j.fct.2006.07.030. PubMed DOI

Ruiz M.J., Macáková P., Juan-García A., Font G. Cytotoxic effects of mycotoxin combinations in mammalian kidney cells. Food Chem. Toxicol. 2011;49:2718–2724. doi: 10.1016/j.fct.2011.07.021. PubMed DOI

Mallebrera B., Prosperini A., Font G., Ruiz M.J. In vitro mechanisms of Beauvericin toxicity: A review. Food Chem. Toxicol. 2018;111:537–545. doi: 10.1016/j.fct.2017.11.019. PubMed DOI

Maranghi F., Tassinari R., Narciso L., Tait S., Rocca C.L., Felice G.D., Butteroni C., Corinti S., Barletta B., Cordelli E., et al. In vivo toxicity and genotoxicity of beauvericin and enniatins. Combined approach to study in vivo toxicity and genotoxicity of mycotoxins beauvericin (BEA) and enniatin B (ENNB) EFSA Support. Publ. 2018;15:1406E. doi: 10.2903/sp.efsa.2018.EN-1406. DOI

Prosperini A., Berrada H., Ruiz M.J., Caloni F., Coccini T., Spicer L.J., Perego M.C., Lafranconi A. A Review of the Mycotoxin Enniatin B. Front. Public Health. 2017;5:1–11. doi: 10.3389/fpubh.2017.00304. PubMed DOI PMC

Wen J., Mu P., Deng Y. Mycotoxins: Cytotoxicity and biotransformation in animal cells. Toxicol. Res. 2016;5:377–387. doi: 10.1039/C5TX00293A. PubMed DOI PMC

Fernández-Blanco C., Juan-García A., Juan C., Font G., Ruiz M.J. Alternariol induce toxicity via cell death and mitochondrial damage on Caco-2 cells. Food Chem. Toxicol. 2016;88:32–39. doi: 10.1016/j.fct.2015.11.022. PubMed DOI

Solhaug A., Eriksen G.S., Holme J.A. Mechanisms of Action and Toxicity of the Mycotoxin Alternariol: A Review. Basic Clin. Pharmacol. Toxicol. 2016;119:533–539. doi: 10.1111/bcpt.12635. PubMed DOI

Nawaz S., Scudamore K.A., Rainbird S.C. Mycotoxins in ingredients of animal feeding stuffs: I. determination of Alternaria mycotoxins in oilseed rape meal and sunflower seed meal. Food Addit. Contam. 1997;14:249–262. doi: 10.1080/02652039709374522. PubMed DOI

Aichinger G., Puntscher H., Beisl J., Kütt M.L., Warth B., Marko D. Delphinidin protects colon carcinoma cells against the genotoxic effects of the mycotoxin altertoxin II. Toxicol. Lett. 2018;284:136–142. doi: 10.1016/j.toxlet.2017.12.002. PubMed DOI

da Motta S., Valente Soares L.M. Survey of Brazilian tomato products for alternariol, alternariol monomethyl ether, tenuazonic acid and cyclopiazonic acid. Food Addit. Contam. 2001;18:630–634. doi: 10.1080/02652030117707. PubMed DOI

Gruber-Dorninger C., Novak B., Nagl V., Berthiller F. Emerging Mycotoxins: Beyond Traditionally Determined Food Contaminants. J. Agric. Food Chem. 2017;65:7052–7070. doi: 10.1021/acs.jafc.6b03413. PubMed DOI

Ge N., Xu J., Peng B., Pan S. Adsorption mechanism of tenuazonic acid using inactivated lactic acid bacteria. Food Control. 2017;82:274–282. doi: 10.1016/j.foodcont.2017.07.009. DOI

Kumari A., Tirkey N.N. Recent Trends in Human and Animal Mycology. Springer; Singapore: 2019. Tenuazonic Acid: A Potent Mycotoxin; pp. 203–211.

Di Gregorio M.C., Bordin K., de Castro Souto P.C.M., Corassin C.H., Oliveira C.A.F. Comparative biotransformation of aflatoxin B 1 in swine, domestic fowls, and humans. Toxin Rev. 2015;34:142–150. doi: 10.3109/15569543.2015.1091979. DOI

Wu T.Y., Fridley B.L., Jenkins G.D., Batzler A., Wang L., Weinshilboum R.M. Mycophenolic acid response biomarkers: A cell line model system-based genome-wide screen. Int. Immunopharmacol. 2011;11:1057–1064. doi: 10.1016/j.intimp.2011.02.027. PubMed DOI PMC

Marin S., Ramos A.J., Cano-Sancho G., Sanchis V. Mycotoxins: Occurrence, toxicology, and exposure assessment. Food Chem. Toxicol. 2013;60:218–237. doi: 10.1016/j.fct.2013.07.047. PubMed DOI

Fraeyman S., Croubels S., Devreese M., Antonissen G. Emerging fusarium and alternaria mycotoxins: Occurrence, toxicity and toxicokinetics. Toxins. 2017;9:228. doi: 10.3390/toxins9070228. PubMed DOI PMC

González-Arias C.A., Crespo-Sempere A., Marín S., Sanchis V., Ramos A.J. Modulation of the xenobiotic transformation system and inflammatory response by ochratoxin A exposure using a co-culture system of Caco-2 and HepG2 cells. Food Chem. Toxicol. 2015;86:245–252. doi: 10.1016/j.fct.2015.10.007. PubMed DOI

Bellí N., Marín S., Sanchis V., Ramos A.J. Ochratoxin A (OTA) in Wines, Musts and Grape Juices: Occurrence, Regulations and Methods of Analysis. Food Sci. Technol. Int. 2002;8:325–335. doi: 10.1177/108201302129174892. DOI

Fernández-Cruz M.L., Mansilla M.L., Tadeo J.L. Mycotoxins in fruits and their processed products: Analysis, occurrence and health implications. J. Adv. Res. 2010;1:113–122. doi: 10.1016/j.jare.2010.03.002. DOI

Orlando B., Grignon G., Vitry C., Kashefifard K., Valade R. Fusarium species and enniatin mycotoxins in wheat, durum wheat, triticale and barley harvested in France. Mycotoxin Res. 2019;35:369–380. doi: 10.1007/s12550-019-00363-x. PubMed DOI

Tibola C.S., de Miranda M.Z., Paiva F.F., Fernandes J.M.C., Guarienti E.M., Nicolau M. Effect of breadmaking process on mycotoxin content in white and whole wheat breads. Cereal Chem. 2018;95:660–665. doi: 10.1002/cche.10079. DOI

Mousavi Khaneghah A., Fakhri Y., Sant’Ana A.S. Impact of unit operations during processing of cereal-based products on the levels of deoxynivalenol, total aflatoxin, ochratoxin A, and zearalenone: A systematic review and meta-analysis. Food Chem. 2018;268:611–624. doi: 10.1016/j.foodchem.2018.06.072. PubMed DOI

Pascari X., Maul R., Kemmlein S., Marin S., Sanchis V. The fate of several trichothecenes and zearalenone during roasting and enzymatic treatment of cereal flour applied in cereal-based infant food production. Food Control. 2020;114:107245. doi: 10.1016/j.foodcont.2020.107245. DOI

Generotti S., Cirlini M., Šarkanj B., Sulyok M., Berthiller F., Dall’Asta C., Suman M. Formulation and processing factors affecting trichothecene mycotoxins within industrial biscuit-making. Food Chem. 2017;229:597–603. doi: 10.1016/j.foodchem.2017.02.115. PubMed DOI

Kuchenbuch H.S., Becker S., Schulz M., Cramer B., Humpf H.U. Thermal stability of t-2 and ht-2 toxins during biscuit-and crunchy muesli-making and roasting. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 2018;35:2158–2167. doi: 10.1080/19440049.2018.1530456. PubMed DOI

Serrano A.B., Font G., Mañes J., Ferrer E. Effects of technological processes on enniatin levels in pasta. J. Sci. Food Agric. 2016;96:1756–1763. doi: 10.1002/jsfa.7282. PubMed DOI

Tolosa J., Font G., Mañes J., Ferrer E. Mitigation of enniatins in edible fish tissues by thermal processes and identification of degradation products. Food Chem. Toxicol. 2017;101:67–74. doi: 10.1016/j.fct.2016.12.039. PubMed DOI

Estiarte N., Crespo-Sempere A., Marín S., Ramos A.J., Worobo R.W. Stability of alternariol and alternariol monomethyl ether during food processing of tomato products. Food Chem. 2018;245:951–957. doi: 10.1016/j.foodchem.2017.11.078. PubMed DOI

Stadler D., Berthiller F., Suman M., Schuhmacher R., Krska R. Novel analytical methods to study the fate of mycotoxins during thermal food processing. Anal. Bioanal. Chem. 2020;412:9–16. doi: 10.1007/s00216-019-02101-9. PubMed DOI PMC

Schaarschmidt S., Fauhl-Hassek C. Mycotoxins during the processes of nixtamalization and tortilla production. Toxins. 2019;11:227. doi: 10.3390/toxins11040227. PubMed DOI PMC

Morcia C., Tumino G., Ghizzoni R., Badeck F.W., Lattanzio V.M.T., Pascale M., Terzi V. Occurrence of Fusarium langsethiae and T-2 and HT-2 toxins in Italian malting barley. Toxins. 2016;8:247. doi: 10.3390/toxins8080247. PubMed DOI PMC

Agriopoulou S., Stamatelopoulou E., Varzakas T. Control Strategies: Prevention and Detoxification in Foods. Foods. 2020;9:137. doi: 10.3390/foods9020137. PubMed DOI PMC

Abrunhosa L., Morales H., Soares C., Calado T., Vila-Chã A.S., Pereira M., Venâncio A. A Review of Mycotoxins in Food and Feed Products in Portugal and Estimation of Probable Daily Intakes. Crit. Rev. Food Sci. Nutr. 2016;56:249–265. doi: 10.1080/10408398.2012.720619. PubMed DOI

Ayelign A., De Saeger S. Mycotoxins in Ethiopia: Current status, implications to food safety and mitigation strategies. Food Control. 2020;113:107163. doi: 10.1016/j.foodcont.2020.107163. DOI

Balendres M.A.O., Karlovsky P., Cumagun C.J.R. Mycotoxigenic fungi and mycotoxins in agricultural crop commodities in the Philippines: A review. Foods. 2019;8:249. doi: 10.3390/foods8070249. PubMed DOI PMC

Puntscher H., Cobankovic I., Marko D., Warth B. Quantitation of free and modified Alternaria mycotoxins in European food products by LC-MS/MS. Food Control. 2019;102:157–165. doi: 10.1016/j.foodcont.2019.03.019. DOI

Meca G., Mañes J., Font G., Ruiz M.J. Study of the potential toxicity of enniatins A, A 1, B, B 1 by evaluation of duodenal and colonic bioavailability applying an invitro method by Caco-2 cells. Toxicon. 2012;59:1–11. doi: 10.1016/j.toxicon.2011.10.004. PubMed DOI

Fernández-García E., Carvajal-Lérida I., Pérez-Gálvez A. In vitro bioaccessibility assessment as a prediction tool of nutritional efficiency. Nutr. Res. 2009;29:751–760. doi: 10.1016/j.nutres.2009.09.016. PubMed DOI

González-Arias C.A., Marín S., Sanchis V., Ramos A.J. Mycotoxin bioaccessibility/absorption assessment using in vitro digestion models: A review. World Mycotoxin J. 2013;6:167–184. doi: 10.3920/WMJ2012.1521. DOI

Brandon E.F.A., Oomen A.G., Rompelberg C.J.M., Versantvoort C.H.M., Van Engelen J.G.M., Sips A.J.A.M. Consumer product in vitro digestion model: Bioaccessibility of contaminants and its application in risk assessment. Regul. Toxicol. Pharmacol. 2006;44:161–171. doi: 10.1016/j.yrtph.2005.10.002. PubMed DOI

Tran V.N., Viktorova J., Augustynkova K., Jelenova N., Dobiasova S., Rehorova K., Fenclova M., Stranska-Zachariasova M., Vitek L., Hajslova J., et al. In silico and in vitro studies of mycotoxins and their cocktails; Their toxicity and its mitigation by silibinin pre-treatment. Toxins. 2020;12:148. doi: 10.3390/toxins12030148. PubMed DOI PMC

Bordin K., Saladino F., Fernández-Blanco C., Ruiz M.J., Mañes J., Fernández-Franzón M., Meca G., Luciano F.B. Reaction of zearalenone and α-zearalenol with allyl isothiocyanate, characterization of reaction products, their bioaccessibility and bioavailability in vitro. Food Chem. 2017;217:648–654. doi: 10.1016/j.foodchem.2016.09.044. PubMed DOI

Kabak B., Brandon E.F.A., Var I., Blokland M., Sips A.J.A.M. Effects of probiotic bacteria on the bioaccessibility of aflatoxin B1 and ochratoxin A using an in vitro digestion model under fed conditions. J. Environ. Sci. Health Part B Pestic. Food Contam. Agric. Wastes. 2009;44:472–480. doi: 10.1080/03601230902935154. PubMed DOI

CenciČ A., Langerholc T. Functional cell models of the gut and their applications in food microbiology—A review. Int. J. Food Microbiol. 2010;141:S4–S14. doi: 10.1016/j.ijfoodmicro.2010.03.026. PubMed DOI PMC

Artursson P., Karlsson J. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem. Biophys. Res. Commun. 1991;175:880–885. doi: 10.1016/0006-291X(91)91647-U. PubMed DOI

Brandon E.F.A., Bosch T.M., Deenen M.J., Levink R., van der Wal E., van Meerveld J.B.M., Bijl M., Beijnen J.H., Schellens J.H.M., Meijerman I. Validation of in vitro cell models used in drug metabolism and transport studies; genotyping of cytochrome P450, phase II enzymes and drug transporter polymorphisms in the human hepatoma (HepG2), ovarian carcinoma (IGROV-1) and colon carcinoma (CaCo-2, LS180) cell lines. Toxicol. Appl. Pharmacol. 2006;211:1–10. PubMed

Lněničková K., Šadibolová M., Matoušková P., Szotáková B., Skálová L., Boušová I. The Modulation of Phase II Drug-Metabolizing Enzymes in Proliferating and Differentiated CaCo-2 Cells by Hop-Derived Prenylflavonoids. Nutrients. 2020;12:2138. doi: 10.3390/nu12072138. PubMed DOI PMC

Schaut A., De Saeger S., Sergent T., Schneider Y.-J., Larondelle Y., Pussemier L., Van Peteghem C. Study of the gastrointestinal biotransformation of zearalenone in a Caco-2 cell culture system with liquid chromatographic methods. J. Appl. Toxicol. 2008;28:966–973. doi: 10.1002/jat.1362. PubMed DOI

Cizkova K. Expression of cytochrome P450 epoxygenases and soluble epoxide hydrolase is regulated by hypolipidemic drugs in dose-dependent manner. Toxicol. Appl. Pharmacol. 2018;355:156–163. doi: 10.1016/j.taap.2018.06.025. PubMed DOI

Šemeláková M., Jendželovský R., Fedoročko P. Drug membrane transporters and CYP3A4 are affected by hypericin, hyperforin or aristoforin in colon adenocarcinoma cells. Biomed. Pharmacother. 2016;81:38–47. doi: 10.1016/j.biopha.2016.03.045. PubMed DOI

Odenthal J., van Heumen B.W.H., Roelofs H.M.J., te Morsche R.H.M., Marian B., Nagengast F.M., Peters W.H.M. The Influence of Curcumin, Quercetin, and Eicosapentaenoic Acid on the Expression of Phase II Detoxification Enzymes in the Intestinal Cell Lines HT-29, Caco-2, HuTu 80, and LT97. Nutr. Cancer. 2012;64:856–863. doi: 10.1080/01635581.2012.700994. PubMed DOI

Langerholc T., Maragkoudakis P.A., Wollgast J., Gradisnik L., Cencic A. Novel and established intestinal cell line models—An indispensable tool in food science and nutrition. Trends Food Sci. Technol. 2011;22:S11–S20. doi: 10.1016/j.tifs.2011.03.010. PubMed DOI PMC

Haslam I.S., Jones K., Coleman T., Simmons N.L. Induction of P-glycoprotein expression and function in human intestinal epithelial cells (T84) Biochem. Pharmacol. 2008;76:850–861. doi: 10.1016/j.bcp.2008.07.020. PubMed DOI

Naruhashi K., Kurahashi Y., Fujita Y., Kawakita E., Yamasaki Y., Hattori K., Nishimura A., Shibata N. Comparison of the Expression and Function of ATP Binding Cassette Transporters in Caco-2 and T84 cells on Stimulation by Selected Endogenous Compounds and Xenobiotics. Drug Metab. Pharmacokinet. 2011;26:145–153. doi: 10.2133/dmpk.DMPK-10-RG-075. PubMed DOI

Theodoropoulos C., Demers C., Delvin E., Menard D., Gascon-Barre M. Calcitriol regulates the expression of the genes encoding the three key vitamin D3 hydroxylases and the drug-metabolizing enzyme CYP3A4 in the human fetal intestine. Clin. Endocrinol. 2003;58:489–499. doi: 10.1046/j.1365-2265.2003.01743.x. PubMed DOI

Saaby L., Helms H.C.C., Brodin B. IPEC-J2 MDR1, a Novel High-Resistance Cell Line with Functional Expression of Human P-glycoprotein (ABCB1) for Drug Screening Studies. Mol. Pharm. 2016;13:640–652. doi: 10.1021/acs.molpharmaceut.5b00874. PubMed DOI

Palócz O., Szita G., Csikó G. Alteration in Inflammatory Responses and Cytochrome P450 Expression of Porcine Jejunal Cells by Drinking Water Supplements. Mediators Inflamm. 2019;2019 doi: 10.1155/2019/5420381. PubMed DOI PMC

Loi M., Fanelli F., Liuzzi V.C., Logrieco A.F., Mulè G. Mycotoxin biotransformation by native and commercial enzymes: Present and future perspectives. Toxins. 2017;9:111. doi: 10.3390/toxins9040111. PubMed DOI PMC

Beyerle J., Frei E., Stiborova M., Habermann N., Ulrich C.M. Biotransformation of xenobiotics in the human colon and rectum and its association with colorectal cancer. Drug Metab. Rev. 2015;47:199–221. doi: 10.3109/03602532.2014.996649. PubMed DOI

Gajecka M., Jakimiuk E., Zielonka L., Obremski K., Gajecka M. The Biotransformation of Chosen Mycotoxins. Pol. J. Vet Sci. 2009;12:293–303. PubMed

Galtier P. Biotransformation and Fate of Mycotoxins. J. Toxicol. Toxin Rev. 1999;18:295–312.

Sergent T., Ribonnet L., Kolosova A., Garsou S., Schaut A., De Saeger S., Van Peteghem C., Larondelle Y., Pussemier L., Schneider Y.J. Molecular and cellular effects of food contaminants and secondary plant components and their plausible interactions at the intestinal level. Food Chem. Toxicol. 2008;46:813–841. doi: 10.1016/j.fct.2007.12.006. PubMed DOI

Lin N.N., Chen J., Xu B., Wei X., Guo L., Xie J.W. The roles of carboxylesterase and CYP isozymes on the in vitro metabolism of T-2 toxin. Mil. Med. Res. 2015;2:13. doi: 10.1186/s40779-015-0041-6. PubMed DOI PMC

Wang J., Jiang J., Zhang H., Wang J., Cai H., Li C., Li K., Liu J., Guo X., Zou G., et al. Integrated transcriptional and proteomic analysis with in vitro biochemical assay reveal the important role of CYP3A46 in T-2 toxin hydroxylation in porcine primary hepatocytes. Mol. Cell. Proteom. 2011;10 doi: 10.1074/mcp.M111.008748. PubMed DOI PMC

Wu Q., Huang L., Liu Z., Yao M., Wang Y., Dai M., Yuan Z. A comparison of hepatic in vitro metabolism of T-2 toxin in rats, pigs, chickens, and carp. Xenobiotica. 2011;41:863–873. doi: 10.3109/00498254.2011.593206. PubMed DOI

Ge X., Wang J., Liu J., Jiang J., Lin H., Wu J., Ouyang M., Tang X., Zheng M., Liao M., et al. The catalytic activity of cytochrome P450 3A22 is critical for the metabolism of T-2 toxin in porcine reservoirs. Catal. Commun. 2010;12:71–75. doi: 10.1016/j.catcom.2010.08.003. DOI

Yuan Y., Zhou X., Yang J., Li M., Qiu X. T-2 toxin is hydroxylated by chicken CYP3A37. Food Chem. Toxicol. 2013;62:622–627. doi: 10.1016/j.fct.2013.09.031. PubMed DOI

Shang S., Jiang J., Deng Y. Chicken cytochrome P450 1A5 is the key enzyme for metabolizing T-2 toxin to 3′OH-T-2. Int. J. Mol. Sci. 2013;14:10809–10818. doi: 10.3390/ijms140610809. PubMed DOI PMC

Dai D., Pan Y., Zeng C.P., Liu S., Yan Y., Wu X., Xu Z., Zhang L. Activated FXR promotes xenobiotic metabolism of T-2 toxin and attenuates oxidative stress in broiler chicken liver. Chem. Biol. Interact. 2020;316:108912. doi: 10.1016/j.cbi.2019.108912. PubMed DOI

Deng Y., Wang Y., Sun L., Lu P., Wang R., Ye L., Xu D., Ye R., Liu Y., Bi S., et al. Biotransformation enzyme activities and phase I metabolites analysis in Litopenaeus vannamei following intramuscular administration of T-2 toxin. Drug Chem. Toxicol. 2018;41:113–122. doi: 10.1080/01480545.2017.1320407. PubMed DOI

Wang Y., Wang G., Dai Y., Wang Y., Lee Y.W., Shi J., Xu J. Biodegradation of Deoxynivalenol by a Novel Microbial Consortium. Front. Microbiol. 2020;10:2964. doi: 10.3389/fmicb.2019.02964. PubMed DOI PMC

Wu Q.H., Wang X., Yang W., Nüssler A.K., Xiong L.Y., Kuča K., Dohnal V., Zhang X.J., Yuan Z.H. Oxidative stress-mediated cytotoxicity and metabolism of T-2 toxin and deoxynivalenol in animals and humans: An update. Arch. Toxicol. 2014;88:1309–1326. doi: 10.1007/s00204-014-1280-0. PubMed DOI

Catteuw A., Broekaert N., De Baere S., Lauwers M., Gasthuys E., Huybrechts B., Callebaut A., Ivanova L., Uhlig S., De Boevre M., et al. Insights into in Vivo Absolute Oral Bioavailability, Biotransformation, and Toxicokinetics of Zearalenone, α-Zearalenol, β-Zearalenol, Zearalenone-14-glucoside, and Zearalenone-14-sulfate in Pigs. J. Agric. Food Chem. 2019;67:3448–3458. doi: 10.1021/acs.jafc.8b05838. PubMed DOI

Malekinejad H., Maas-Bakker R., Fink-Gremmels J. Species differences in the hepatic biotransformation of zearalenone. Vet. J. 2006;172:96–102. doi: 10.1016/j.tvjl.2005.03.004. PubMed DOI

Malekinejad H., Maas-Bakker R.F., Fink-Gremmels J. Bioactivation of zearalenone by porcine hepatic biotransformation. Vet. Res. 2005;36:799–810. doi: 10.1051/vetres:2005034. PubMed DOI

Ayed-Boussema I., Pascussi J.M., Maurel P., Bacha H., Hassen W. Zearalenone activates pregnane X receptor, constitutive androstane receptor and aryl hydrocarbon receptor and corresponding phase I target genes mRNA in primary cultures of human hepatocytes. Environ. Toxicol. Pharmacol. 2011;31:79–87. doi: 10.1016/j.etap.2010.09.008. PubMed DOI

Rodríguez-Carrasco Y., Heilos D., Richter L., Süssmuth R.D., Heffeter P., Sulyok M., Kenner L., Berger W., Dornetshuber-Fleiss R. Mouse tissue distribution and persistence of the food-born fusariotoxins Enniatin B and Beauvericin. Toxicol. Lett. 2016;247:35–44. doi: 10.1016/j.toxlet.2016.02.008. PubMed DOI PMC

Mei L., Zhang L., Dai R. An inhibition study of beauvericin on human and rat cytochrome P450 enzymes and its pharmacokinetics in rats. J. Enzym. Inhib. Med. Chem. 2009;24:753–762. doi: 10.1080/14756360802362041. PubMed DOI

Fæste C.K., Ivanova L., Uhlig S. In vitro metabolism of the mycotoxin enniatin B in different species and cytochrome P450 enzyme phenotyping by chemical inhibitors. Drug Metab. Dispos. 2011;39:1768–1776. doi: 10.1124/dmd.111.039529. PubMed DOI

Ivanova L., Fæste C.K., Uhlig S. In vitro phase i metabolism of the depsipeptide enniatin B. Anal. Bioanal. Chem. 2011;400:2889–2901. doi: 10.1007/s00216-011-4964-9. PubMed DOI

Ivanova L., Fæste C.K., Van Pamel E., Daeseleire E., Callebaut A., Uhlig S. Presence of enniatin B and its hepatic metabolites in plasma and liver samples from broilers and eggs from laying hens. World Mycotoxin J. 2014;7:167–175. doi: 10.3920/WMJ2013.1609. DOI

Ivanova L., Denisov I.G., Grinkova Y.V., Sligar S.G., Fæste C.K. Biotransformation of the Mycotoxin Enniatin B1 by CYP P450 3A4 and Potential for Drug-Drug Interactions. Metabolites. 2019;9:158. doi: 10.3390/metabo9080158. PubMed DOI PMC

Ivanova L., Uhlig S., Devreese M., Croubels S., Fæste C.K. Biotransformation of the mycotoxin enniatin B1 in pigs: A comparative in vitro and in vivo approach. Food Chem. Toxicol. 2017;105:506–517. doi: 10.1016/j.fct.2017.04.041. PubMed DOI

Debevere S., Cools A., De Baere S., Haesaert G., Rychlik M., Croubels S., Fievez V. In Vitro Rumen Simulations Show a Reduced Disappearance of Deoxynivalenol, Nivalenol and Enniatin B at Conditions of Rumen Acidosis and Lower Microbial Activity. Toxins. 2020;12:101. doi: 10.3390/toxins12020101. PubMed DOI PMC

Fraeyman S., Devreese M., Antonissen G., De Baere S., Rychlik M., Croubels S. Comparative Oral Bioavailability, Toxicokinetics, and Biotransformation of Enniatin B1 and Enniatin B in Broiler Chickens. J. Agric. Food Chem. 2016;64:7259–7264. doi: 10.1021/acs.jafc.6b02913. PubMed DOI

Müller S., Dekant W., Mally A. Fumonisin B 1 and the kidney: Modes of action for renal tumor formation by fumonisin B 1 in rodents. Food Chem. Toxicol. 2012;50:3833–3846. doi: 10.1016/j.fct.2012.06.053. PubMed DOI

Schreck I., Deigendesch U., Burkhardt B., Marko D., Weiss C. The Alternaria mycotoxins alternariol and alternariol methyl ether induce cytochrome P450 1A1 and apoptosis in murine hepatoma cells dependent on the aryl hydrocarbon receptor. Arch. Toxicol. 2012;86:625–632. doi: 10.1007/s00204-011-0781-3. PubMed DOI

Aichinger G., Krüger F., Puntscher H., Preindl K., Warth B., Marko D. Naturally occurring mixtures of Alternaria toxins: Anti-estrogenic and genotoxic effects in vitro. Arch. Toxicol. 2019;93:3021–3031. doi: 10.1007/s00204-019-02545-z. PubMed DOI

Burkhardt B., Pfeiffer E., Metzler M. Absorption and metabolism of the mycotoxins alternariol and alternariol-9-methyl ether in Caco-2 cells in vitro. Mycotoxin Res. 2009;25:149–157. doi: 10.1007/s12550-009-0022-2. PubMed DOI

Scheibenzuber S., Hoffmann T., Effenberger I., Schwab W., Asam S., Rychlik M. Enzymatic synthesis of modified alternaria mycotoxins using a whole-cell biotransformation system. Toxins. 2020;12:264. doi: 10.3390/toxins12040264. PubMed DOI PMC

Puntscher H., Hankele S., Tillmann K., Attakpah E., Braun D., Kütt M.L., Del Favero G., Aichinger G., Pahlke G., Höger H., et al. First insights into Alternaria multi-toxin in vivo metabolism. Toxicol. Lett. 2019;301:168–178. doi: 10.1016/j.toxlet.2018.10.006. PubMed DOI

Yang X.J., Lu H.Y., Li Z.Y., Bian Q., Qiu L.L., Li Z., Liu Q., Li J., Wang X., Wang S.L. Cytochrome P450 2A13 mediates aflatoxin B1-induced cytotoxicity and apoptosis in human bronchial epithelial cells. Toxicology. 2012;300:138–148. doi: 10.1016/j.tox.2012.06.010. PubMed DOI

Deng J., Zhao L., Zhang N.Y., Karrow N.A., Krumm C.S., Qi D.S., Sun L.H. Aflatoxin B 1 metabolism: Regulation by phase I and II metabolizing enzymes and chemoprotective agents. Mutat. Res. Rev. Mutat. Res. 2018;778:79–89. doi: 10.1016/j.mrrev.2018.10.002. PubMed DOI

Ayed-Boussema I., Pascussi J.M., Zaied C., Maurel P., Bacha H., Hassen W. Ochratoxin A induces CYP3A4, 2B6, 3A5, 2C9, 1A1, and CYP1A2 gene expression in primary cultured human hepatocytes: A possible activation of nuclear receptors. Drug Chem. Toxicol. 2012;35:71–80. doi: 10.3109/01480545.2011.589438. PubMed DOI

Shin H.S., Lee H.J., Pyo M.C., Ryu D., Lee K.W. Ochratoxin a-induced hepatotoxicity through phase i and phase ii reactions regulated by ahr in liver cells. Toxins. 2019;11:377. doi: 10.3390/toxins11070377. PubMed DOI PMC

Tao Y., Xie S., Xu F., Liu A., Wang Y., Chen D., Pan Y., Huang L., Peng D., Wang X., et al. Ochratoxin A: Toxicity, oxidative stress and metabolism. Food Chem. Toxicol. 2018;112:320–331. doi: 10.1016/j.fct.2018.01.002. PubMed DOI

Gross-Steinmeyer K., Weymann J., Hege H.G., Metzler M. Metabolism and lack of DNA reactivity of the mycotoxin ochratoxin A in cultured rat and human primary hepatocytes. J. Agric. Food Chem. 2002;50:938–945. doi: 10.1021/jf0111817. PubMed DOI

Tozlovanu M., Canadas D., Pfohl-Leszkowicz A., Frenette C., Paugh R.J., Manderville R.A. Glutathione conjugates of ochratoxin a as biomarkers of exposure. Arh. Hig. Rada Toksikol. 2012;63:417–425. doi: 10.2478/10004-1254-63-2012-2202. PubMed DOI

Kőszegi T., Poór M. Ochratoxin a: Molecular interactions, mechanisms of toxicity and prevention at the molecular level. Toxins. 2016;8:111. doi: 10.3390/toxins8040111. PubMed DOI PMC

Ayed-Boussema I., Pascussi J.M., Rjiba K., Maurel P., Bacha H., Hassen W. The mycotoxin, patulin, increases the expression of PXR and AhR and their target cytochrome P450s in primary cultured human hepatocytes. Drug Chem. Toxicol. 2012;35:241–250. doi: 10.3109/01480545.2011.592194. PubMed DOI

Ji C., Fan Y., Zhao L. Review on biological degradation of mycotoxins. Anim. Nutr. 2016;2:127–133. doi: 10.1016/j.aninu.2016.07.003. PubMed DOI PMC

Young J.C., Zhou T., Yu H., Zhu H., Gong J. Degradation of trichothecene mycotoxins by chicken intestinal microbes. Food Chem. Toxicol. 2007;45:136–143. doi: 10.1016/j.fct.2006.07.028. PubMed DOI

Pierron A., Mimoun S., Murate L.S., Loiseau N., Lippi Y., Bracarense A.P.F.L., Schatzmayr G., He J.W., Zhou T., Moll W.D., et al. Microbial biotransformation of DON: Molecular basis for reduced toxicity. Sci. Rep. 2016;6:29105. doi: 10.1038/srep29105. PubMed DOI PMC

Du K., Wang C., Liu P., Li Y., Ma X. Effects of Dietary Mycotoxins on Gut Microbiome. Protein Pept. Lett. 2017;24:397–405. doi: 10.2174/0929866524666170223095207. PubMed DOI

Antonissen G., Devreese M., De Baere S., Martel A., Van Immerseel F., Croubels S. Impact of Fusarium mycotoxins on hepatic and intestinal mRNA expression of cytochrome P450 enzymes and drug transporters, and on the pharmacokinetics of oral enrofloxacin in broiler chickens. Food Chem. Toxicol. 2017;101:75–83. doi: 10.1016/j.fct.2017.01.006. PubMed DOI

Murcia H.W., Diaz G.J. In vitro hepatic aflatoxicol production is related to a higher resistance to aflatoxin B1 in poultry. Sci. Rep. 2020;10:5508. doi: 10.1038/s41598-020-62415-y. PubMed DOI PMC

Gross-Steinmeyer K., Eaton D.L. Dietary modulation of the biotransformation and genotoxicity of aflatoxin B1. Toxicology. 2012;299:69–79. doi: 10.1016/j.tox.2012.05.016. PubMed DOI

Peles F., Sipos P., Győri Z., Pfliegler W.P., Giacometti F., Serraino A., Pagliuca G., Gazzotti T., Pócsi I. Adverse Effects, Transformation and Channeling of Aflatoxins Into Food Raw Materials in Livestock. Front. Microbiol. 2019;10:1–26. doi: 10.3389/fmicb.2019.02861. PubMed DOI PMC

Wu J., Xu W., Zhang C., Chang Q., Tang X., Li K., Deng Y. Trp266 determines the binding specificity of a porcine aflatoxin B 1 aldehyde reductase for aflatoxin B1-dialdehyde. Biochem. Pharmacol. 2013;86:1357–1365. doi: 10.1016/j.bcp.2013.08.014. PubMed DOI

Lyagin I., Efremenko E. Enzymes for Detoxification of Various Mycotoxins: Origins and Mechanisms of Catalytic Action. Molecules. 2019;24:2362. doi: 10.3390/molecules24132362. PubMed DOI PMC

Schrenk D., Bodin L., Chipman J.K., del Mazo J., Grasl-Kraupp B., Hogstrand C., Hoogenboom L. (Ron), Leblanc J., Nebbia C.S., Nielsen E., et al. Risk assessment of ochratoxin A in food. EFSA J. 2020;18 doi: 10.2903/j.efsa.2020.6113. PubMed DOI PMC

Li P., Su R., Yin R., Lai D., Wang M., Liu Y., Zhou L. Detoxification of mycotoxins through biotransformation. Toxins. 2020;12:121. doi: 10.3390/toxins12020121. PubMed DOI PMC

Ringot D., Chango A., Schneider Y.-J., Larondelle Y. Toxicokinetics and toxicodynamics of ochratoxin A, an update. Chem. Biol. Interact. 2006;159:18–46. doi: 10.1016/j.cbi.2005.10.106. PubMed DOI

Wu Q., Dohnal V., Huang L., Kuca K., Wang X., Chen G., Yuan Z. Metabolic Pathways of Ochratoxin A. Curr. Drug Metab. 2011;12:1–10. doi: 10.2174/138920011794520026. PubMed DOI

Schelstraete W., Devreese M., Croubels S. Impact of subacute exposure to T-2 toxin and zearalenone on the pharmacokinetics of midazolam as CYP3A probe drug in a porcine animal model: A pilot study. Front. Pharmacol. 2019;10:399. doi: 10.3389/fphar.2019.00399. PubMed DOI PMC

Payros D., Alassane-Kpembi I., Pierron A., Loiseau N., Pinton P., Oswald I.P. Toxicology of deoxynivalenol and its acetylated and modified forms. Arch. Toxicol. 2016;90:2931–2957. doi: 10.1007/s00204-016-1826-4. PubMed DOI

Springler A., Hessenberger S., Reisinger N., Kern C., Nagl V., Schatzmayr G., Mayer E. Deoxynivalenol and its metabolite deepoxy-deoxynivalenol: Multi-parameter analysis for the evaluation of cytotoxicity and cellular effects. Mycotoxin Res. 2017;33:25–37. doi: 10.1007/s12550-016-0260-z. PubMed DOI PMC

Nagl V., Woechtl B., Schwartz-Zimmermann H.E., Hennig-Pauka I., Moll W.D., Adam G., Berthiller F. Metabolism of the masked mycotoxin deoxynivalenol-3-glucoside in pigs. Toxicol. Lett. 2014;229:190–197. doi: 10.1016/j.toxlet.2014.06.032. PubMed DOI

Schwartz H.E., Hametner C., Slavik V., Greitbauer O., Bichl G., Kunz-Vekiru E., Schatzmayr D., Berthiller F. Characterization of three deoxynivalenol sulfonates formed by reaction of deoxynivalenol with sulfur reagents. J. Agric. Food Chem. 2013;61:8941–8948. doi: 10.1021/jf403438b. PubMed DOI

Gerding J., Cramer B., Humpf H.U. Determination of mycotoxin exposure in Germany using an LC-MS/MS multibiomarker approach. Mol. Nutr. Food Res. 2014;58:2358–2368. doi: 10.1002/mnfr.201400406. PubMed DOI

Pestka J.J. Deoxynivalenol: Toxicity, mechanisms and animal health risks. Anim. Feed Sci. Technol. 2007;137:283–298. doi: 10.1016/j.anifeedsci.2007.06.006. DOI

Gao X., Mu P., Zhu X., Chen X., Tang S., Wu Y., Miao X., Wang X., Wen J., Deng Y. Dual function of a novel bacterium, slackia sp. D-G6: Detoxifying deoxynivalenol and producing the Natural Estrogen Analogue, Equol. Toxins. 2020;12:85. doi: 10.3390/toxins12020085. PubMed DOI PMC

Mackei M., Orbán K., Molnár A., Pál L., Dublecz K., Husvéth F., Neogrády Z., Mátis G. Cellular Effects of T-2 Toxin on Primary Hepatic Cell Culture Models of Chickens. Toxins. 2020;12:46. doi: 10.3390/toxins12010046. PubMed DOI PMC

Li Y., Wang Z., Beier R.C., Shen J., De Smet D., De Saeger S., Zhang S. T-2 toxin, a trichothecene mycotoxin: Review of toxicity, metabolism, and analytical methods. J. Agric. Food Chem. 2011;59:3441–3453. doi: 10.1021/jf200767q. PubMed DOI

Welsch T., Humpf H.U. HT-2 toxin 4-glucuronide as new T-2 toxin metabolite: Enzymatic synthesis, analysis, and species specific formation of T-2 and HT-2 toxin glucuronides by rat, mouse, pig, and human liver microsomes. J. Agric. Food Chem. 2012;60:10170–10178. doi: 10.1021/jf302571y. PubMed DOI

Masching S., Naehrer K., Schwartz-Zimmermann H.E., Sărăndan M., Schaumberger S., Dohnal I., Nagl V., Schatzmayr D. Gastrointestinal degradation of fumonisin B1 by carboxylesterase FumD prevents fumonisin induced alteration of sphingolipid metabolism in Turkey and swine. Toxins. 2016;8:84. doi: 10.3390/toxins8030084. PubMed DOI PMC

Daud N., Currie V., Duncan G., Busman M., Gratz S.W. Intestinal hydrolysis and microbial biotransformation of diacetoxyscirpenol-α-glucoside, HT-2-β-glucoside and N-(1-deoxy-d-fructos-1-yl) fumonisin B1 by human gut microbiota in vitro. Int. J. Food Sci. Nutr. 2019;71:540–548. doi: 10.1080/09637486.2019.1698015. PubMed DOI

Merrill A.H., Morgan E.T., Nikolova-Karakashian M., Stewart J. Sphingomyelin hydrolysis and regulation of the expression of the gene for cytochrome P450. Biochem. Soc. Trans. 1999;27:383–387. doi: 10.1042/bst0270383. PubMed DOI

Spotti M., Maas R.F.M., De Nijs C.M., Fink-Gremmels J. Effect of fumonisin B1 on rat hepatic P450 system. Environ. Toxicol. Pharmacol. 2000;8:197–204. doi: 10.1016/S1382-6689(00)00040-5. PubMed DOI

Riley R.T., Merrill A.H. Ceramide synthase inhibition by fumonisins: A perfect storm of perturbed sphingolipid metabolism, signaling, and disease. J. Lipid Res. 2019;60:1183–1189. doi: 10.1194/jlr.S093815. PubMed DOI PMC

Harrer H., Laviad E.L., Humpf H.U., Futerman A.H. Identification of N-acyl-fumonisin B1 as new cytotoxic metabolites of fumonisin mycotoxins. Mol. Nutr. Food Res. 2013;57:516–522. doi: 10.1002/mnfr.201200465. PubMed DOI

Dellafiora L., Galaverna G., Dall’Asta C. Mechanisms of Fumonisin B1 Toxicity: A Computational Perspective beyond the Ceramide Synthases Inhibition. Chem. Res. Toxicol. 2018;31:1203–1212. doi: 10.1021/acs.chemrestox.8b00188. PubMed DOI

Knutsen H.K., Alexander J., Barregård L., Bignami M., Brüschweiler B., Ceccatelli S., Cottrill B., Dinovi M., Edler L., Grasl-Kraupp B., et al. Risks for animal health related to the presence of fumonisins, their modified forms and hidden forms in feed. EFSA J. 2018;16:e05242. PubMed PMC

Ieko T., Inoue S., Inomata Y., Inoue H., Fujiki J., Iwano H. Glucuronidation as a metabolic barrier against zearalenone in rat everted intestine. J. Vet. Med. Sci. 2020;82:153–161. doi: 10.1292/jvms.19-0570. PubMed DOI PMC

Binder S.B., Schwartz-Zimmermann H.E., Varga E., Bichl G., Michlmayr H., Adam G., Berthiller F. Metabolism of zearalenone and its major modified forms in pigs. Toxins. 2017;9:56. doi: 10.3390/toxins9020056. PubMed DOI PMC

Videmann B., Mazallon M., Tep J., Lecoeur S. Metabolism and transfer of the mycotoxin zearalenone in human intestinal Caco-2 cells. Food Chem. Toxicol. 2008;46:3279–3286. doi: 10.1016/j.fct.2008.07.011. PubMed DOI

Dellafiora L., Galaverna G., Righi F., Cozzini P., Dall’Asta C. Assessing the hydrolytic fate of the masked mycotoxin zearalenone-14-glucoside—A warning light for the need to look at the “maskedome”. Food Chem. Toxicol. 2017;99:9–16. doi: 10.1016/j.fct.2016.11.013. PubMed DOI

Keller L., Abrunhosa L., Keller K., Rosa C., Cavaglieri L., Venâncio A. Zearalenone and Its Derivatives α-Zearalenol and β-Zearalenol Decontamination by Saccharomyces cerevisiae Strains Isolated from Bovine Forage. Toxins. 2015;7:3297–3308. doi: 10.3390/toxins7083297. PubMed DOI PMC

Rogowska A., Pomastowski P., Walczak J., Railean-Plugaru V., Rudnicka J., Buszewski B. Investigation of zearalenone adsorption and biotransformation by microorganisms cultured under cellular stress conditions. Toxins. 2019;11:463. doi: 10.3390/toxins11080463. PubMed DOI PMC

Rogowska A., Pomastowski P., Rafińska K., Railean-Plugaru V., Złoch M., Walczak J., Buszewski B. A study of zearalenone biosorption and metabolisation by prokaryotic and eukaryotic cells. Toxicon. 2019;169:81–90. doi: 10.1016/j.toxicon.2019.09.008. PubMed DOI

Chlebicz A., Śliżewska K. In Vitro Detoxification of Aflatoxin B1, Deoxynivalenol, Fumonisins, T-2 Toxin and Zearalenone by Probiotic Bacteria from Genus Lactobacillus and Saccharomyces cerevisiae Yeast. Probiotics Antimicrob. Proteins. 2020;12:289–301. doi: 10.1007/s12602-018-9512-x. PubMed DOI PMC

Pfeiffer E., Schebb N.H., Podlech J., Metzler M. Novel oxidative in vitro metabolites of the mycotoxins alternariol and alternariol methyl ether. Mol. Nutr. Food Res. 2007;51:307–316. doi: 10.1002/mnfr.200600237. PubMed DOI

Pfeiffer E., Burkhardt B., Altemöller M., Podlech J., Metzler M. Activities of human recombinant cytochrome P450 isoforms and human hepatic microsomes for the hydroxylation ofAlternaria toxins. Mycotoxin Res. 2008;24:117–123. doi: 10.1007/BF03032337. PubMed DOI

Tiessen C., Ellmer D., Mikula H., Pahlke G., Warth B., Gehrke H., Zimmermann K., Heiss E., Fröhlich J., Marko D. Impact of phase I metabolism on uptake, oxidative stress and genotoxicity of the emerging mycotoxin alternariol and its monomethyl ether in esophageal cells. Arch. Toxicol. 2017;91:1213–1226. doi: 10.1007/s00204-016-1801-0. PubMed DOI PMC

Lemke A., Burkhardt B., Bunzel D., Pfeiffer E., Metzler M., Huch M., Kulling S.E., Franz C.M.A.P. Alternaria toxins of the alternariol type are not metabolised by human faecal microbiota. World Mycotoxin J. 2016;9:41–49. doi: 10.3920/WMJ2014.1875. DOI

Fleck S.C., Pfeiffer E., Podlech J., Metzler M. Epoxide Reduction to an Alcohol: A Novel Metabolic Pathway for Perylene Quinone-Type Alternaria Mycotoxins in Mammalian Cells. Chem. Res. Toxicol. 2014;27:247–253. doi: 10.1021/tx400366w. PubMed DOI

Burkhardt B., Wittenauer J., Pfeiffer E., Schauer U.M.D., Metzler M. Oxidative metabolism of the mycotoxins alternariol and alternariol-9-methyl ether in precision-cut rat liver slices in vitro. Mol. Nutr. Food Res. 2011;55:1079–1086. doi: 10.1002/mnfr.201000487. PubMed DOI

Pfeiffer E., Schmit C., Burkhardt B., Altemöller M., Podlech J., Metzler M. Glucuronidation of the mycotoxins alternariol and alternariol-9-methyl ether in vitro: Chemical structures of glucuronides and activities of human UDP-glucuronosyltransferase isoforms. Mycotoxin Res. 2009;25:3–10. doi: 10.1007/s12550-008-0001-z. PubMed DOI

Soukup S.T., Kohn B.N., Pfeiffer E., Geisen R., Metzler M., Bunzel M., Kulling S.E. Sulfoglucosides as Novel Modified Forms of the Mycotoxins Alternariol and Alternariol Monomethyl Ether. J. Agric. Food Chem. 2016;64:8892–8901. doi: 10.1021/acs.jafc.6b03120. PubMed DOI

Puntscher H., Marko D., Warth B. The fate of altertoxin ii during tomato processing steps at a laboratory scale. Front. Nutr. 2019;6:92. doi: 10.3389/fnut.2019.00092. PubMed DOI PMC

Pfeiffer E., Herrmann C., Altemöller M., Podlech J., Metzler M. Oxidative in vitro metabolism of the Alternaria toxins altenuene and isoaltenuene. Mol. Nutr. Food Res. 2009;53:452–459. doi: 10.1002/mnfr.200700501. PubMed DOI

Rychlik M., Kircher F., Schusdziarra V., Lippl F. Absorption of the mycotoxin patulin from the rat stomach. Food Chem. Toxicol. 2004;42:729–735. doi: 10.1016/j.fct.2003.12.015. PubMed DOI

Rychlik M. Rapid degradation of the mycotoxin patulin in man quantified by stable isotope dilution assays. Food Addit. Contam. 2003;20:829–837. doi: 10.1080/0265203031000152424. PubMed DOI

Zheng X., Wei W., Rao S., Gao L., Li H., Yang Z. Degradation of patulin in fruit juice by a lactic acid bacteria strain Lactobacillus casei YZU01. Food Control. 2020;112:107147. doi: 10.1016/j.foodcont.2020.107147. DOI

Tannous J., Snini S.P., El Khoury R., Canlet C., Pinton P., Lippi Y., Alassane-Kpembi I., Gauthier T., El Khoury A., Atoui A., et al. Patulin transformation products and last intermediates in its biosynthetic pathway, E- and Z-ascladiol, are not toxic to human cells. Arch. Toxicol. 2017;91:2455–2467. doi: 10.1007/s00204-016-1900-y. PubMed DOI

Ianiri G., Idnurm A., Wright S.A.I., Durán-Patrón R., Mannina L., Ferracane R., Ritieni A., Castoria R. Searching for genes responsible for patulin degradation in a biocontrol yeast provides insight into the basis for resistance to this mycotoxin. Appl. Environ. Microbiol. 2013;79:3101–3115. doi: 10.1128/AEM.03851-12. PubMed DOI PMC

Xu R., Zhu H., Hu L., Yu B., Zhan X., Yuan Y., Zhou P. Characterization of the intestinal absorption of morroniside from Cornus officinalis Sieb. et Zucc via a Caco-2 cell monolayer model. PLoS ONE. 2020;15:e0227844. doi: 10.1371/journal.pone.0227844. PubMed DOI PMC

Zhang J., Zheng N., Liu J., Li F.D., Li S.L., Wang J.Q. Aflatoxin B1 and aflatoxin M1 induced cytotoxicity and DNA damage in differentiated and undifferentiated Caco-2 cells. Food Chem. Toxicol. 2015;83:54–60. doi: 10.1016/j.fct.2015.05.020. PubMed DOI

Fogh J., Fogh J.M., Orfeo T. One Hundred and Twenty-Seven Cultured Human Tumor Cell Lines Producing Tumors in Nude Mice23. JNCI J. Natl. Cancer Inst. 1977;59:221–226. doi: 10.1093/jnci/59.1.221. PubMed DOI

Iftikhar M., Iftikhar A., Zhang H., Gong L., Wang J. Transport, metabolism and remedial potential of functional food extracts (FFEs) in Caco-2 cells monolayer: A Review. Food Res. Int. 2020;136:109240. doi: 10.1016/j.foodres.2020.109240. PubMed DOI

Kamiloglu S., Capanoglu E., Grootaert C., Van Camp J. Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells—A Review. Int. J. Mol. Sci. 2015;16:21555–21574. doi: 10.3390/ijms160921555. PubMed DOI PMC

Awortwe C., Fasinu P.S., Rosenkranz B. Application of Caco-2 cell line in herb-drug interaction studies: Current approaches and challenges. J. Pharm. Pharm. Sci. Publ. Can. Soc. Pharm. Sci. Société Can. Sci. Pharm. 2014;17:1–19. doi: 10.18433/J30K63. PubMed DOI PMC

Wang X., Li L., Zhang G. Impact of deoxynivalenol and kaempferol on expression of tight junction proteins at different stages of Caco-2 cell proliferation and differentiation. RSC Adv. 2019;9:34607–34616. doi: 10.1039/C9RA06222J. PubMed DOI PMC

Wang X., Li L., Zhang G. A proteomic study on the protective effect of kaempferol pretreatment against deoxynivalenol-induced intestinal barrier dysfunction in a Caco-2 cell model. Food Funct. 2020;11:7266–7279. doi: 10.1039/D0FO01579B. PubMed DOI

Akbari P., Braber S., Varasteh S., Alizadeh A., Garssen J., Fink-Gremmels J. The intestinal barrier as an emerging target in the toxicological assessment of mycotoxins. Arch. Toxicol. 2017;91:1007–1029. doi: 10.1007/s00204-016-1794-8. PubMed DOI PMC

Alizadeh A., Akbari P., Varasteh S., Braber S., Malekinejad H., Fink-Gremmels J. Ochratoxin A challenges the intestinal epithelial cell integrity: Results obtained in model experiments with Caco-2 cells. World Mycotoxin J. 2019;12:399–407. doi: 10.3920/WMJ2019.2451. DOI

Pinton P., Nougayrède J.P., Del Rio J.C., Moreno C., Marin D.E., Ferrier L., Bracarense A.P., Kolf-Clauw M., Oswald I.P. The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression. Toxicol. Appl. Pharmacol. 2009;237:41–48. doi: 10.1016/j.taap.2009.03.003. PubMed DOI

Romero A., Ares I., Ramos E., Castellano V., Martínez M.M.A., Martínez-Larrañaga M.R., Anadón A., Martínez M.M.A. Mycotoxins modify the barrier function of Caco-2 cells through differential gene expression of specific claudin isoforms: Protective effect of illite mineral clay. Toxicology. 2016;353–354:21–33. doi: 10.1016/j.tox.2016.05.003. PubMed DOI

Sun H., Chow E.C.Y., Liu S., Du Y., Pang K.S. The Caco-2 cell monolayer: Usefulness and limitations. Expert Opin. Drug Metab. Toxicol. 2008;4:395–411. doi: 10.1517/17425255.4.4.395. PubMed DOI

Ferruzza S., Scarino M.L., Gambling L., Natella F., Sambuy Y. Biphasic effect of iron on human intestinal Caco-2 cells: Early effect on tight junction permeability with delayed onset of oxidative cytotoxic damage. Cell. Mol. Biol. 2003;49:89–99. PubMed

Videmann B., Tep J., Cavret S., Lecoeur S. Epithelial transport of deoxynivalenol: Involvement of human P-glycoprotein (ABCB1) and multidrug resistance-associated protein 2 (ABCC2) Food Chem. Toxicol. 2007;45:1938–1947. doi: 10.1016/j.fct.2007.04.011. PubMed DOI

Sergent T., Parys M., Garsou S., Pussemier L., Schneider Y.J., Larondelle Y. Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations. Toxicol. Lett. 2006;164:167–176. doi: 10.1016/j.toxlet.2005.12.006. PubMed DOI

Artursson P., Palm K., Luthman K. Caco-2 monolayers in experimental and theoretical predictions of drug transport. Adv. Drug Deliv. Rev. 2012;22:280–289. doi: 10.1016/j.addr.2012.09.005. PubMed DOI

Kadota T., Furusawa H., Hirano S., Tajima O., Kamata Y., Sugita-Konishi Y. Comparative study of deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol on intestinal transport and IL-8 secretion in the human cell line Caco-2. Toxicol. In Vitro. 2013;27:1888–1895. doi: 10.1016/j.tiv.2013.06.003. PubMed DOI

Sobral M.M.C., Faria M.A., Cunha S.C., Miladinovic B., Ferreira I.M. Transport of mycotoxins across human gastric NCI–N87 and intestinal Caco-2 cell models. Food Chem. Toxicol. 2019;131:110595. doi: 10.1016/j.fct.2019.110595. PubMed DOI

Tep J., Videmann B., Mazallon M., Balleydier S., Cavret S., Lecoeur S. Transepithelial transport of fusariotoxin nivalenol: Mediation of secretion by ABC transporters. Toxicol. Lett. 2007;170:248–258. doi: 10.1016/j.toxlet.2007.03.012. PubMed DOI

Pfeiffer E., Kommer A., Dempe J.S., Hildebrand A.A., Metzler M. Absorption and metabolism of the mycotoxin zearalenone and the growth promotor zeranol in Caco-2 cells in vitro. Mol. Nutr. Food Res. 2011;55:560–567. doi: 10.1002/mnfr.201000381. PubMed DOI

Cirlini M., Barilli A., Galaverna G., Michlmayr H., Adam G., Berthiller F., Dall’Asta C. Study on the uptake and deglycosylation of the masked forms of zearalenone in human intestinal Caco-2 cells. Food Chem. Toxicol. 2016;98:232–239. doi: 10.1016/j.fct.2016.11.003. PubMed DOI

Prosperini A., Meca G., Font G., Ruiz M.J. Study of the cytotoxic activity of beauvericin and fusaproliferin and bioavailability in vitro on Caco-2 cells. Food Chem. Toxicol. 2012;50:2356–2361. doi: 10.1016/j.fct.2012.04.030. PubMed DOI

De Angelis I., Friggè G., Raimondi F., Stammati A., Zucco F., Caloni F. Absorption of Fumonisin B1 and aminopentol on an in vitro model of intestinal epithelium; the role of P-glycoprotein. Toxicon. 2005;45:285–291. doi: 10.1016/j.toxicon.2004.10.015. PubMed DOI

Berger V., Gabriel A.F., Sergent T., Trouet A., Larondelle Y., Schneider Y.J. Interaction of ochratoxin A with human intestinal Caco-2 cells: Possible implication of a multidrug resistance-associated protein (MRP2) Toxicol. Lett. 2003;140–141:465–476. doi: 10.1016/S0378-4274(03)00043-2. PubMed DOI

De Walle J.V., Sergent T., Piront N., Toussaint O., Schneider Y.-J., Larondelle Y. Deoxynivalenol affects in vitro intestinal epithelial cell barrier integrity through inhibition of protein synthesis. Toxicol. Appl. Pharmacol. 2010;245:291–298. doi: 10.1016/j.taap.2010.03.012. PubMed DOI

De Nijs M., Van Den Top H.J., Portier L., Oegema G., Kramer E., Van Egmond H.P., Hoogenboom L.A.P. Digestibility and absorption of deoxynivalenol-3-ß-glucoside in in vitro models. World Mycotoxin J. 2012;5:319–324. doi: 10.3920/WMJ2012.1430. DOI

Schrickx J., Lektarau Y., Fink-Gremmels J. Ochratoxin A secretion by ATP-dependent membrane transporters in Caco-2 cells. Arch. Toxicol. 2006;80:243–249. doi: 10.1007/s00204-005-0041-5. PubMed DOI

Tuntiteerawit P., Jarukamjorn K., Porasuphatana S. The effect of green tea catechins on breast cancer resistance protein activity and intestinal efflux of aflatoxin B1 via breast cancer resistance protein in Caco-2 cells. Toxicol. Res. 2020;36:293–300. doi: 10.1007/s43188-019-00032-2. PubMed DOI PMC

Li X., Mu P., Wen J., Deng Y. Carrier-Mediated and Energy-Dependent Uptake and Efflux of Deoxynivalenol in Mammalian Cells. Sci. Rep. 2017;7:1–10. doi: 10.1038/s41598-017-06199-8. PubMed DOI PMC

Li X., Mu P., Qiao H., Wen J., Deng Y. JNK-AKT-NF-κB controls P-glycoprotein expression to attenuate the cytotoxicity of deoxynivalenol in mammalian cells. Biochem. Pharmacol. 2018;156:120–134. doi: 10.1016/j.bcp.2018.08.020. PubMed DOI

Ivanova L., Fæste C.K., Solhaug A. Role of P-glycoprotein in deoxynivalenol-mediated in vitro toxicity. Toxicol. Lett. 2018;284:21–28. doi: 10.1016/j.toxlet.2017.11.021. PubMed DOI

Anderle P., Niederer E., Rubas W., Hilgendorf C., Spahn-Langguth H., Wunderli-Allenspach H., Merkle H.P., Langguth P. P-glycoprotein (P-gp) mediated efflux in Caco-2 cell monolayers: The influence of culturing conditions and drug exposure on P-gp expression levels. J. Pharm. Sci. 1998;87:757–762. doi: 10.1021/js970372e. PubMed DOI

Videmann B., Mazallon M., Prouillac C., Delaforge M., Lecoeur S. ABCC1, ABCC2 and ABCC3 are implicated in the transepithelial transport of the myco-estrogen zearalenone and its major metabolites. Toxicol. Lett. 2009;190:215–223. doi: 10.1016/j.toxlet.2009.07.021. PubMed DOI

Xu R., Karrow N.A., Shandilya U.K., Sun L.H., Kitazawa H. In-vitro cell culture for efficient assessment of mycotoxin exposure, toxicity and risk mitigation. Toxins. 2020;12:146. doi: 10.3390/toxins12030146. PubMed DOI PMC

Gao Y., Li S., Wang J., Luo C., Zhao S., Zheng N. Modulation of intestinal epithelial permeability in differentiated caco-2 cells exposed to aflatoxin M1 and ochratoxin a individually or collectively. Toxins. 2018;10:13. doi: 10.3390/toxins10010013. PubMed DOI PMC

Marin D., Motiu M., Taranu I. Food Contaminant Zearalenone and Its Metabolites Affect Cytokine Synthesis and Intestinal Epithelial Integrity of Porcine Cells. Toxins. 2015;7:1979–1988. doi: 10.3390/toxins7061979. PubMed DOI PMC

Bouhet S., Hourcade E., Loiseau N., Fikry A., Roselli M., Galtier P., Mengheri E., Oswald I.P., Martinez S., Roselli M., et al. The mycotoxin fumonisin B1 alters the proliferation and the barrier function of porcine intestinal epithelial cells. Toxicol. Sci. 2004;77:165–171. doi: 10.1093/toxsci/kfh006. PubMed DOI

Pinton P., Braicu C., Nougayrede J.-P., Laffitte J., Taranu I., Oswald I.P. Deoxynivalenol Impairs Porcine Intestinal Barrier Function and Decreases the Protein Expression of Claudin-4 through a Mitogen-Activated Protein Kinase-Dependent Mechanism. J. Nutr. 2010;140:1956–1962. doi: 10.3945/jn.110.123919. PubMed DOI

Madara J.L. Regulation of the Movement of Solutes Across Tight Junctions. Annu. Rev. Physiol. 1998;60:143–159. doi: 10.1146/annurev.physiol.60.1.143. PubMed DOI

Gao Y.N., Wang J.Q., Li S.L., Zhang Y.D., Zheng N. Aflatoxin M1 cytotoxicity against human intestinal Caco-2 cells is enhanced in the presence of other mycotoxins. Food Chem. Toxicol. 2016;96:79–89. doi: 10.1016/j.fct.2016.07.019. PubMed DOI

Fleck S.C., Pfeiffer E., Metzler M. Permeation and metabolism of Alternaria mycotoxins with perylene quinone structure in cultured Caco-2 cells. Mycotoxin Res. 2014;30:17–23. doi: 10.1007/s12550-013-0180-0. PubMed DOI

González-Arias C.A., Marín S., Rojas-García A.E., Sanchis V., Ramos A.J. UPLC-MS/MS analysis of ochratoxin A metabolites produced by Caco-2 and HepG2 cells in a co-culture system. Food Chem. Toxicol. 2017;109:333–340. doi: 10.1016/j.fct.2017.09.011. PubMed DOI

Matter K., Balda M.S. Signalling to and from tight junctions. Nat. Rev. Mol. Cell Biol. 2003;4:225–237. doi: 10.1038/nrm1055. PubMed DOI

Moon Y. Vomitoxin-Induced Cyclooxygenase-2 Gene Expression in Macrophages Mediated by Activation of ERK and p38 but Not JNK Mitogen-Activated Protein Kinases. Toxicol. Sci. 2002;69:373–382. doi: 10.1093/toxsci/69.2.373. PubMed DOI

Zhou H.-R., Jia Q., Pestka J.J. Ribotoxic Stress Response to the Trichothecene Deoxynivalenol in the Macrophage Involves the Src Family Kinase Hck. Toxicol. Sci. 2005;85:916–926. doi: 10.1093/toxsci/kfi146. PubMed DOI

Pinton P., Graziani F., Pujol A., Nicoletti C., Paris O., Ernouf P., Di Pasquale E., Perrier J., Oswald I.P., Maresca M. Deoxynivalenol inhibits the expression by goblet cells of intestinal mucins through a PKR and MAP kinase dependent repression of the resistin-like molecule β. Mol. Nutr. Food Res. 2015;59:1076–1087. doi: 10.1002/mnfr.201500005. PubMed DOI

Morrison D.K. MAP Kinase Pathways. Cold Spring Harb. Perspect. Biol. 2012;4:a011254. doi: 10.1101/cshperspect.a011254. PubMed DOI PMC

Lee J.Y., Lim W., Park S., Kim J., You S., Song G. Deoxynivalenol induces apoptosis and disrupts cellular homeostasis through MAPK signaling pathways in bovine mammary epithelial cells. Environ. Pollut. 2019;252:879–887. doi: 10.1016/j.envpol.2019.06.001. PubMed DOI

Bouhet S., Le E., Peres S., Fairbrother J.M., Oswald I.P., Hyacinthe S. Mycotoxin fumonisin B 1 selectively down-regulates the basal IL-8 expression in pig intestine: In vivo and in vitro studies. Food Chem. Toxicol. 2006;44:1768–1773. doi: 10.1016/j.fct.2006.05.018. PubMed DOI

Beisl J., Pahlke G., Abeln H., Ehling-Schulz M., Del Favero G., Varga E., Warth B., Sulyok M., Abia W., Ezekiel C.N., et al. Combinatory effects of cereulide and deoxynivalenol on in vitro cell viability and inflammation of human Caco-2 cells. Arch. Toxicol. 2020;94:833–844. doi: 10.1007/s00204-020-02658-w. PubMed DOI

Pellegrina C.D., Perbellini O., Scupoli M.T., Tomelleri C., Zanetti C., Zoccatelli G., Fusi M., Peruffo A., Rizzi C., Chignola R. Effects of wheat germ agglutinin on human gastrointestinal epithelium: Insights from an experimental model of immune/epithelial cell interaction. Toxicol. Appl. Pharmacol. 2009;237:146–153. doi: 10.1016/j.taap.2009.03.012. PubMed DOI

Gao Y., Ye Q., Bao X., Huang X., Wang J., Zheng N. Transcriptomic and proteomic profiling reveals the intestinal immunotoxicity induced by aflatoxin M1 and ochratoxin A. Toxicon. 2020;180:49–61. doi: 10.1016/j.toxicon.2020.03.008. PubMed DOI

Trapecar M., Cencic A. Application of Gut Cell Models for Toxicological and Bioactivity Studies of Functional and Novel Foods. Foods. 2014;1:40–51. doi: 10.3390/foods1010040. PubMed DOI PMC

Fu J., Cui Y. In vitro digestion/Caco-2 cell model to estimate cadmium and lead bioaccessibility/bioavailability in two vegetables: The influence of cooking and additives. Food Chem. Toxicol. 2013;59:215–221. doi: 10.1016/j.fct.2013.06.014. PubMed DOI

Ekmekcioglu C. A physiological approach for preparing and conducting intestinal bioavailability studies using experimental systems. Food Chem. 2002;76:225–230. doi: 10.1016/S0308-8146(01)00291-6. DOI

Seithel A., Karlsson J., Hilgendorf C., Bj A., Ungell A.-L., Björquist A., Ungell A.-L. Variability in mRNA expression of ABC- and SLC-transporters in human intestinal cells: Comparison between human segments and Caco-2 cells. Eur. J. Pharm. Sci. 2006;28:291–299. doi: 10.1016/j.ejps.2006.03.003. PubMed DOI

Taipalensuu J., Törnblom H., Lindberg G., Einarsson C., Sjöqvist F., Melhus H., Garberg P., Sjöström B., Lundgren B., Artursson P. Correlation of Gene Expression of Ten Drug Efflux Proteins of the ATP-Binding Cassette Transporter Family in Normal Human Jejunum and in Human Intestinal Epithelial Caco-2 Cell Monolayers. J. Pharmacol. Exp. Ther. 2001;299:164–170. PubMed

Lampen A., Bader A., Bestmann T., Winkler M., Witte L., Borlak J.T. Catalytic activities, protein- and mRNA-expression of cytochrome P450 isoenzymes in intestinal cell lines. Xenobiotica. 1998;28:429–441. doi: 10.1080/004982598239362. PubMed DOI

Caloni F., Cortinovis C., Pizzo F., De Angelis I. Transport of aflatoxin M1 in human intestinal Caco-2/TC7 cells. Front. Pharmacol. 2012;3:111. doi: 10.3389/fphar.2012.00111. PubMed DOI PMC

Wu C., Gao Y., Li S., Huang X., Bao X., Wang J., Zheng N. Modulation of intestinal epithelial permeability and mucin mRNA (MUC2, MUC5AC, and MUC5B) expression and protein secretion in Caco-2/HT29-MTX co-cultures exposed to aflatoxin M1, ochratoxin A, and zearalenone individually or collectively. Toxicol. Lett. 2019;309:1–9. doi: 10.1016/j.toxlet.2019.03.010. PubMed DOI

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...