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Prof. Doris Marko
University of Vienna

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0 Food Safety
0 Mycotoxins
0 anthocyanins
0 chemical mixtures
0 food-drug interaction

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Mycotoxins
topoisomerases
anthocyanins
Food Safety
chemical mixtures

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Short Biography

Doris Marko is Prof. for Food Chemistry and Head of the Institute of Food Chemistry and Toxicology, Faculty of Chemistry at the University of Vienna, Austria. She studied Food Chemistry at the University of Kaiserslautern, Germany. Starting in the field of preclinical drug development, she acquired profound expertise in the elucidation of molecular mechanism of bioactive constituents arising from natural sources focusing predominantly on anticarcinogenic and chemopreventive effects. The research strategy aims at substantiation of beneficial health effects ranging from basic molecular models to the development of respective in vivo biomarkers, but also includes the assessment of potentially undesired application-limiting effects.

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Journal article
Published: 29 July 2021 in Comprehensive Reviews in Food Science and Food Safety
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Alternaria molds are known to cause the contamination of food with their secondary metabolites, a chemically very heterogeneous group of compounds. Yet, after decades of research on the occurrence and the toxicity of Alternaria toxins in academia, no regulation has been implemented yet, thus leaving these potential food contaminants in the status of so-called “emerging mycotoxins”. However, research on this topic has been far from static, leading to the European Food Safety Authority repeatedly calling for more data on the occurrence and toxicity of genotoxic metabolites such as alternariol (AOH) and its monomethyl ether (AME). To give an overview on recent developments in the field, this comprehensive review summarizes published data and addresses current challenges arising from the chemical complexity of Alternaria’s metabolome, mixture effects and the emergence of novel biological targets like cell membranes or the interaction with different receptors. Besides toxicodynamics, we review recent research on toxicokinetics, including the first in vivo studies which incorporated the rarely investigated—but highly genotoxic—perylene quinones. Furthermore, a particular focus lies on the advances of liquid chromatography/tandem mass spectrometry (LC-MS/MS)-based analytical tools for determining a broader spectrum of Alternaria toxins including modified/masked forms and assessing exposure via human biomonitoring (HBM).

ACS Style

Georg Aichinger; Giorgia Del Favero; Benedikt Warth; Doris Marko. Alternaria toxins—Still emerging? Comprehensive Reviews in Food Science and Food Safety 2021, 1 .

AMA Style

Georg Aichinger, Giorgia Del Favero, Benedikt Warth, Doris Marko. Alternaria toxins—Still emerging? Comprehensive Reviews in Food Science and Food Safety. 2021; ():1.

Chicago/Turabian Style

Georg Aichinger; Giorgia Del Favero; Benedikt Warth; Doris Marko. 2021. "Alternaria toxins—Still emerging?" Comprehensive Reviews in Food Science and Food Safety , no. : 1.

Research article
Published: 02 July 2021 in Molecular Nutrition & Food Research
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Scope Glycosylation is a way to increase structure-stability of anthocyanins, yet compromises their bioactivity. We investigated the antioxidant activity of purified cyanidin (Cy)-based anthocyanins and respective degradation products in Caco-2 clone C2BBe1 aiming to identify structure-activity relationships. Results and methods Cyanidin 3-O-glucoside (Cy-3-glc) and cyanidin 3-O-sambubioside (Cy-3-sam) proved to be most potent regarding antioxidant properties and protection against hydrogen peroxide (H2O2)-induced reactive oxygen species (ROS)-levels measured with the dichloro-fluorescein assay. Cyanidin 3-O-sambubioside-5-O-glucoside (Cy-3-sam-5-glc) and cyanidin 3-O-rutinoside (Cy-3-rut) were less efficient and not protective, reflecting potential differences in uptake and/or degradation. Following ranking in antioxidant efficiency is suggested: (concentrations ≤ 10 μM) Cy-3-glc ≥ Cy-3-sam > Cy-3-sam-5-glc ≈ Cy-3-rut ≈ Cy; (concentrations ≥ 50 μM) Cy-3-glc ≈ Cy-3-sam ≥ Cy > Cy-3-sam-5-glc ≈ Cy-3-rut. Cyanidin and protocatechuic acid reduced ROS-levels as potent as the mono- and di-glycoside, whereas phloroglucinol aldehyde displayed prooxidant properties. None of the degradation products protected from oxidative stress. Gene transcription analysis of catalase, superoxide-dismutase, glutathione-peroxidase, heme-oxygenase-1 and glutamate-cysteine-ligase suggest no activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Conclusion More complex residues and numbers of sugar moieties appear to be counterproductive for antioxidant activity. Other mechanisms than Nrf2-activation should be considered for protective effects. This article is protected by copyright. All rights reserved

ACS Style

Gudrun Pahlke; Katarina Ahlberg; Anne Oertel; Theresa Janson‐Schaffer; Stephanie Grabher; Hans‐Peter Mock; Andrea Matros; Doris Marko. Antioxidant Effects of Elderberry Anthocyanins in Human Colon Carcinoma Cells: A Study on Structure‐Activity Relationships. Molecular Nutrition & Food Research 2021, 2100229 .

AMA Style

Gudrun Pahlke, Katarina Ahlberg, Anne Oertel, Theresa Janson‐Schaffer, Stephanie Grabher, Hans‐Peter Mock, Andrea Matros, Doris Marko. Antioxidant Effects of Elderberry Anthocyanins in Human Colon Carcinoma Cells: A Study on Structure‐Activity Relationships. Molecular Nutrition & Food Research. 2021; ():2100229.

Chicago/Turabian Style

Gudrun Pahlke; Katarina Ahlberg; Anne Oertel; Theresa Janson‐Schaffer; Stephanie Grabher; Hans‐Peter Mock; Andrea Matros; Doris Marko. 2021. "Antioxidant Effects of Elderberry Anthocyanins in Human Colon Carcinoma Cells: A Study on Structure‐Activity Relationships." Molecular Nutrition & Food Research , no. : 2100229.

Nutrition
Published: 07 June 2021 in Frontiers in Nutrition
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Some prenylated polyphenols originating from hops, which are thus natural constituents of beer, have been discussed critically for their agonistic potential toward estrogen receptors. So far, little attention has been attributed to the fact that humans are typically not exposed to isolated compounds, but to mixtures which for example might comprise in addition to hop flavonoids further xenoestrogens, e.g., certain pesticides used for plant protection of hops and barley. Thus, we used the alkaline phosphatase assay to assess combinatory estrogenic effects of three signature compounds – xanthohumol, 8-prenylnaringenin and iso-xanthohumol–on Ishikawa cells in a combination that resembled the concentration ratios observable in beer. Moreover, we added this natural flavonoid pattern to a mixture of representative estrogenic pesticides to assess their combined effects. Using state-of-the-art statistical tools, we observed cumulative to slightly synergistic effects between isolated flavonoids as well as the flavonoid and the pesticide mixture. Of potential importance, these effects were found at low nanomolar hop polyphenol concentrations that one can reasonably expect to occur in vivo after the consumption of strongly hopped beer. Taken together, our results imply that cumulative/synergistic estrogenicity should be explored in detail and urgently be incorporated into risk assessment of prenylated chalcones.

ACS Style

Georg Aichinger; Gloria Bliem; Doris Marko. Systemically Achievable Doses of Beer Flavonoids Induce Estrogenicity in Human Endometrial Cells and Cause Synergistic Effects With Selected Pesticides. Frontiers in Nutrition 2021, 8, 1 .

AMA Style

Georg Aichinger, Gloria Bliem, Doris Marko. Systemically Achievable Doses of Beer Flavonoids Induce Estrogenicity in Human Endometrial Cells and Cause Synergistic Effects With Selected Pesticides. Frontiers in Nutrition. 2021; 8 ():1.

Chicago/Turabian Style

Georg Aichinger; Gloria Bliem; Doris Marko. 2021. "Systemically Achievable Doses of Beer Flavonoids Induce Estrogenicity in Human Endometrial Cells and Cause Synergistic Effects With Selected Pesticides." Frontiers in Nutrition 8, no. : 1.

Biologics
Published: 23 April 2021 in Archives of Toxicology
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Deoxynivalenol (vomitoxin, DON) is a secondary metabolite produced by Fusarium spp. fungi and it is one of the most prevalent mycotoxins worldwide. Crop infestation results not only in food and feed contamination, but also in direct dermal exposure, especially during harvest and food processing. To investigate the potential dermotoxicity of DON, epidermoid squamous cell carcinoma cells A431 were compared to primary human neonatal keratinocytes (HEKn) cells via proteome/phosphoproteome profiling. In A431 cells, 10 µM DON significantly down-regulated ribosomal proteins, as well as mitochondrial respiratory chain elements (OXPHOS regulation) and transport proteins (TOMM22; TOMM40; TOMM70A). Mitochondrial impairment was reflected in altered metabolic competence, apparently combined with interference of the lipid biosynthesis machinery. Functional effects on the cell membrane were confirmed by live cell imaging and membrane fluidity assays (0.1–10 µM DON). Moreover, a common denominator for both A431 and HEKn cells was a significant downregulation of the squalene synthase (FDFT1). In sum, proteome alterations could be traced back to the transcription factor Klf4, a crucial regulator of skin barrier function. Overall, these results describe decisive molecular events sustaining the capability of DON to impair skin barrier function. Proteome data generated in the study are fully accessible via ProteomeXchange with the accession numbers PXD011474 and PXD013613.

ACS Style

Giorgia Del Favero; Lukas Janker; Benjamin Neuditschko; Julia Hohenbichler; Endre Kiss; Lydia Woelflingseder; Christopher Gerner; Doris Marko. Exploring the dermotoxicity of the mycotoxin deoxynivalenol: combined morphologic and proteomic profiling of human epidermal cells reveals alteration of lipid biosynthesis machinery and membrane structural integrity relevant for skin barrier function. Archives of Toxicology 2021, 95, 2201 -2221.

AMA Style

Giorgia Del Favero, Lukas Janker, Benjamin Neuditschko, Julia Hohenbichler, Endre Kiss, Lydia Woelflingseder, Christopher Gerner, Doris Marko. Exploring the dermotoxicity of the mycotoxin deoxynivalenol: combined morphologic and proteomic profiling of human epidermal cells reveals alteration of lipid biosynthesis machinery and membrane structural integrity relevant for skin barrier function. Archives of Toxicology. 2021; 95 (6):2201-2221.

Chicago/Turabian Style

Giorgia Del Favero; Lukas Janker; Benjamin Neuditschko; Julia Hohenbichler; Endre Kiss; Lydia Woelflingseder; Christopher Gerner; Doris Marko. 2021. "Exploring the dermotoxicity of the mycotoxin deoxynivalenol: combined morphologic and proteomic profiling of human epidermal cells reveals alteration of lipid biosynthesis machinery and membrane structural integrity relevant for skin barrier function." Archives of Toxicology 95, no. 6: 2201-2221.

Biologics
Published: 13 April 2021 in Archives of Toxicology
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The human gut microbiota plays an important role in the maintenance of human health. Factors able to modify its composition might predispose the host to the development of pathologies. Among the various xenobiotics introduced through the diet, Alternaria mycotoxins are speculated to represent a threat for human health. However, limited data are currently available about the bidirectional relation between gut microbiota and Alternaria mycotoxins. In the present work, we investigated the in vitro effects of different concentrations of a complex extract of Alternaria mycotoxins (CE; containing eleven mycotoxins; e.g. 0.153 µM alternariol and 2.3 µM altersetin, at the maximum CE concentration tested) on human gut bacterial strains, as well as the ability of the latter to metabolize or adsorb these compounds. Results from the minimum inhibitory concentration assay showed the scarce ability of CE to inhibit the growth of the tested strains. However, the growth kinetics of most of the strains were negatively affected by exposure to the various CE concentrations, mainly at the highest dose (50 µg/mL). The CE was also found to antagonize the formation of biofilms, already at concentrations of 0.5 µg/mL. LC–MS/MS data analysis of the mycotoxin concentrations found in bacterial pellets and supernatants after 24 h incubation showed the ability of bacterial strains to adsorb some Alternaria mycotoxins, especially the key toxins alternariol, alternariol monomethyl ether, and altersetin. The tendency of these mycotoxins to accumulate within bacterial pellets, especially in those of Gram-negative strains, was found to be directly related to their lipophilicity.

ACS Style

Francesco Crudo; Georg Aichinger; Jovana Mihajlovic; Elisabeth Varga; Luca Dellafiora; Benedikt Warth; Chiara Dall’Asta; David Berry; Doris Marko. In vitro interactions of Alternaria mycotoxins, an emerging class of food contaminants, with the gut microbiota: a bidirectional relationship. Archives of Toxicology 2021, 95, 2533 -2549.

AMA Style

Francesco Crudo, Georg Aichinger, Jovana Mihajlovic, Elisabeth Varga, Luca Dellafiora, Benedikt Warth, Chiara Dall’Asta, David Berry, Doris Marko. In vitro interactions of Alternaria mycotoxins, an emerging class of food contaminants, with the gut microbiota: a bidirectional relationship. Archives of Toxicology. 2021; 95 (7):2533-2549.

Chicago/Turabian Style

Francesco Crudo; Georg Aichinger; Jovana Mihajlovic; Elisabeth Varga; Luca Dellafiora; Benedikt Warth; Chiara Dall’Asta; David Berry; Doris Marko. 2021. "In vitro interactions of Alternaria mycotoxins, an emerging class of food contaminants, with the gut microbiota: a bidirectional relationship." Archives of Toxicology 95, no. 7: 2533-2549.

Journal article
Published: 04 March 2021 in Toxins
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The human intestine is regularly exposed to ingested food contaminants, such as fungal and bacterial toxins, which have been described to co-occur in a mixed diet. Thus, it is of utmost importance to understand possible interactions between contaminants of different origin. Hence, we investigated the single and combined effects of one of the most abundant mycotoxins, deoxynivalenol (DON; 0.1 to 10 µg/mL), and the bacterial toxin cereulide (CER; 1 to 100 ng/mL) on differentiated human Caco-2 (C2BBe1) cells cultured in a transwell system. We tested the capacity of the two toxins to alter the intestinal integrity and further investigated the uptake of both compounds and the formation of selected DON metabolites. CER alone (10 and 100 ng/mL) and in combination with DON (10 ng/mL CER with 1 µg/mL DON) was found to alter the barrier function by increasing the transepithelial electrical resistance and the expression of the tight junction protein claudin-4. For the first time, DON-3-sulfate was identified as a metabolite of human intestinal cells in vitro. Moreover, co-incubation of CER and DON led to an altered ratio between DON and DON-3-sulfate. Hence, we conclude that co-exposure to CER and DON may alter the intestinal barrier function and biotransformation of intestinal cells.

ACS Style

Julia Beisl; Elisabeth Varga; Dominik Braun; Benedikt Warth; Monika Ehling-Schulz; Giorgia Del Favero; Doris Marko. Assessing Mixture Effects of Cereulide and Deoxynivalenol on Intestinal Barrier Integrity and Uptake in Differentiated Human Caco-2 Cells. Toxins 2021, 13, 189 .

AMA Style

Julia Beisl, Elisabeth Varga, Dominik Braun, Benedikt Warth, Monika Ehling-Schulz, Giorgia Del Favero, Doris Marko. Assessing Mixture Effects of Cereulide and Deoxynivalenol on Intestinal Barrier Integrity and Uptake in Differentiated Human Caco-2 Cells. Toxins. 2021; 13 (3):189.

Chicago/Turabian Style

Julia Beisl; Elisabeth Varga; Dominik Braun; Benedikt Warth; Monika Ehling-Schulz; Giorgia Del Favero; Doris Marko. 2021. "Assessing Mixture Effects of Cereulide and Deoxynivalenol on Intestinal Barrier Integrity and Uptake in Differentiated Human Caco-2 Cells." Toxins 13, no. 3: 189.

Original research article
Published: 12 January 2021 in Frontiers in Plant Science
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While aflatoxin metabolism in animals has been clarified, very limited information is so far available on the possible biotransformation occurring in plants. Therefore, this work aimed at investigating whether AFB1 metabolites could occur in field-grown infected maize and the putative role of Zea mays L. metabolism in their production. For such scope, asymptomatic in vitro–grown plantlets and in silico evaluations of plant transforming enzymes were used to pinpoint how plants may handle these compounds. Our data demonstrated the role of maize plants in the production of Phase I hydroxylated aflatoxins, including, among others, AFM1, AFM2, and aflatoxicol, and suggest that plant cytochromes may be involved in this biotransformation of AFB1.

ACS Style

Laura Righetti; Enrico Rolli; Luca Dellafiora; Gianni Galaverna; Michele Suman; Renato Bruni; Chiara Dall’Asta. Thinking Out of the Box: On the Ability of Zea mays L. to Biotrasform Aflatoxin B1 Into Its Modified Forms. Frontiers in Plant Science 2021, 11, 1 .

AMA Style

Laura Righetti, Enrico Rolli, Luca Dellafiora, Gianni Galaverna, Michele Suman, Renato Bruni, Chiara Dall’Asta. Thinking Out of the Box: On the Ability of Zea mays L. to Biotrasform Aflatoxin B1 Into Its Modified Forms. Frontiers in Plant Science. 2021; 11 ():1.

Chicago/Turabian Style

Laura Righetti; Enrico Rolli; Luca Dellafiora; Gianni Galaverna; Michele Suman; Renato Bruni; Chiara Dall’Asta. 2021. "Thinking Out of the Box: On the Ability of Zea mays L. to Biotrasform Aflatoxin B1 Into Its Modified Forms." Frontiers in Plant Science 11, no. : 1.

Original article
Published: 09 January 2021 in The Plant Journal
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To cope with the presence of unfavorable compounds, plants are capable to biotransform xenobiotics, translocate both parent compounds and metabolites, perform compartmentation and segregation at cellular or tissue level. Such a scenario also applies to mycotoxins, fungal secondary metabolites with a preeminent role in plant infection. In this work, we aimed to describe the effect of the interplay between Zea mays and aflatoxin B1 (AFB1) at the tissue and organ level. To address this challenge, we used atmospheric‐pressure scanning microprobe matrix‐assisted laser desorption/ionization mass spectrometry imaging (AP‐SMALDI MSI) to investigate in situ and from a metabolomic standpoint the biotransformation, localization and the subsequent effects of AFB1 on primary and secondary metabolism of healthy maize plants. High spatial resolution (5 µm) provided fine localization of AFB1, which was located within the root intercellular spaces, and co‐localized with its phase I metabolite aflatoxin M2. We provided a parallel visualization of maize metabolic changes, induced in different organs and tissues by an accumulation of AFB1. According to our untargeted metabolomics investigation, anthocyanin biosynthesis and chlorophyll metabolism in roots are most affected. The biosynthesis of these metabolites appears to be inhibited by the AFB1 accumulation. On the other hand, metabolites found in above‐ground organs suggest that the presence of AFB1 may activate the biochemical response also in absence of an actual fungal infection; indeed several plant secondary metabolites known for their antimicrobial or antioxidant activities were localized in the outer tissues, such as phenylpropanoids, benzoxazinoid, phytohormones and lipids.

ACS Style

Laura Righetti; Dhaka Ram Bhandari; Enrico Rolli; Sara Tortorella; Renato Bruni; Chiara Dall’Asta; Bernhard Spengler. Unveiling the spatial distribution of aflatoxin B1 and plant defense metabolites in maize using AP‐SMALDI mass spectrometry imaging. The Plant Journal 2021, 106, 185 -199.

AMA Style

Laura Righetti, Dhaka Ram Bhandari, Enrico Rolli, Sara Tortorella, Renato Bruni, Chiara Dall’Asta, Bernhard Spengler. Unveiling the spatial distribution of aflatoxin B1 and plant defense metabolites in maize using AP‐SMALDI mass spectrometry imaging. The Plant Journal. 2021; 106 (1):185-199.

Chicago/Turabian Style

Laura Righetti; Dhaka Ram Bhandari; Enrico Rolli; Sara Tortorella; Renato Bruni; Chiara Dall’Asta; Bernhard Spengler. 2021. "Unveiling the spatial distribution of aflatoxin B1 and plant defense metabolites in maize using AP‐SMALDI mass spectrometry imaging." The Plant Journal 106, no. 1: 185-199.

Journal article
Published: 06 January 2021 in Toxicology Letters
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Alternariol is a mycotoxin produced by Alternaria spp. relevant to the food safety area due to its abundance in certain foods. The shortage of data on its toxicology, also as a part of chemical mixtures, prevents setting regulation to limit its abundance in food. To extend knowledge on the possible mechanisms underpinning alternariol toxicology in chemical mixtures, this work assessed the effects of urolithin C, a structurally related gut ellagitannin-derived metabolite, on its absorption and phase II metabolism in a monolayer of Caco-2 cells. A computational study was also used to provide a mechanistic explanation for the results obtained. Urolithin C influenced transport and phase II metabolism of alternariol with a late reduction of transport to the basolateral compartment. Moreover, it caused an early effect in terms of accumulation of alternariol glucuronides in the basolateral compartment, followed by a late reduction of glucuronides in both compartments. Concerning alternariol sulfates, the data collected pointed to a possible competition of urolithin C for the sulfotransferases resulting in a reduced production of alternariol sulfates. Our results provide a compelling line-of-evidence pointing to the need to systematically tackle the evaluation of mycotoxin toxicity in the context of chemical mixture.

ACS Style

Francesco Crudo; Amelia Barilli; Pedro Mena; Bianca Maria Rotoli; Daniele Del Rio; Chiara Dall’Asta; Luca Dellafiora. An in vitro study on the transport and phase II metabolism of the mycotoxin alternariol in combination with the structurally related gut microbial metabolite urolithin C. Toxicology Letters 2021, 340, 15 -22.

AMA Style

Francesco Crudo, Amelia Barilli, Pedro Mena, Bianca Maria Rotoli, Daniele Del Rio, Chiara Dall’Asta, Luca Dellafiora. An in vitro study on the transport and phase II metabolism of the mycotoxin alternariol in combination with the structurally related gut microbial metabolite urolithin C. Toxicology Letters. 2021; 340 ():15-22.

Chicago/Turabian Style

Francesco Crudo; Amelia Barilli; Pedro Mena; Bianca Maria Rotoli; Daniele Del Rio; Chiara Dall’Asta; Luca Dellafiora. 2021. "An in vitro study on the transport and phase II metabolism of the mycotoxin alternariol in combination with the structurally related gut microbial metabolite urolithin C." Toxicology Letters 340, no. : 15-22.

Review
Published: 04 January 2021 in Foods
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The aim of this study is to review the innovative techniques based on bioprocessing, thermal or physical treatments which have been proposed during the last few decades to convert rice bran into a valuable food ingredient. Rice bran (Oryza sativa) is the main by-product of rice grain processing. It is produced in large quantities worldwide and it contains a high amount of valuable nutrients and bioactive compounds with significant health-related properties. Despite that, its application in food industry is still scarce because of its sensitivity to oxidation processes, instability and poor technological suitability. Furthermore, the health-related effects of pretreated rice bran are also presented in this review, considering the up-to-date literature focused on both in vivo and in vitro studies. Moreover, in relation to this aspect, a brief description of rice bran arabinoxylans is provided. Finally, the application of rice bran in the food industry and the main technology aspects are concisely summarized.

ACS Style

Marco Spaggiari; Chiara Dall’Asta; Gianni Galaverna; María Dolores Del Castillo Bilbao. Rice Bran By-Product: From Valorization Strategies to Nutritional Perspectives. Foods 2021, 10, 85 .

AMA Style

Marco Spaggiari, Chiara Dall’Asta, Gianni Galaverna, María Dolores Del Castillo Bilbao. Rice Bran By-Product: From Valorization Strategies to Nutritional Perspectives. Foods. 2021; 10 (1):85.

Chicago/Turabian Style

Marco Spaggiari; Chiara Dall’Asta; Gianni Galaverna; María Dolores Del Castillo Bilbao. 2021. "Rice Bran By-Product: From Valorization Strategies to Nutritional Perspectives." Foods 10, no. 1: 85.

Preprint content
Published: 03 January 2021
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We demonstrate a path towards full Quantum Mechanics (QM) characterization of enzymatic activity. As a case-study, we investigate the detoxification of aflatoxin, a carcinogenic food contaminant, by laccase, a versatile oxidase capable of—but not efficient for—degrading aflatoxin. We use a combination of quantitative experimentation and QM modeling to show that low enzymatic steric affinity for aflatoxin is the main bottleneck, rather that the oxidative activity of laccase. To identify the structural elements responsible for low reaction rates, we perform a density functional theory (DFT) based modeling of both the substrate and the enzyme in a full QM simulation of more than 7,000 atoms. Thanks to our approach we point to amino acid residues that determine the affinity of laccase for aflatoxin. We show that these residues are substrate-dependent, making a full QM approach necessary for enzyme optimization. Altogether, we establish a roadmap for rational enzyme engineering applicable beyond our case study.

ACS Style

Marco Zaccaria; William Dawson; Darius Russell Kish; Massimo Reverberi; Maria Carmela Bonaccorsi Di Patti; Marek Domin; Viviana Cristiglio; Luca Dellafiora; Frank Gabel; Takahito Nakajima; Luigi Genovese; Babak Momeni. Mechanistic Insight from Full Quantum Mechanical Modeling: Laccase as a Detoxifier of Aflatoxins. 2021, 1 .

AMA Style

Marco Zaccaria, William Dawson, Darius Russell Kish, Massimo Reverberi, Maria Carmela Bonaccorsi Di Patti, Marek Domin, Viviana Cristiglio, Luca Dellafiora, Frank Gabel, Takahito Nakajima, Luigi Genovese, Babak Momeni. Mechanistic Insight from Full Quantum Mechanical Modeling: Laccase as a Detoxifier of Aflatoxins. . 2021; ():1.

Chicago/Turabian Style

Marco Zaccaria; William Dawson; Darius Russell Kish; Massimo Reverberi; Maria Carmela Bonaccorsi Di Patti; Marek Domin; Viviana Cristiglio; Luca Dellafiora; Frank Gabel; Takahito Nakajima; Luigi Genovese; Babak Momeni. 2021. "Mechanistic Insight from Full Quantum Mechanical Modeling: Laccase as a Detoxifier of Aflatoxins." , no. : 1.

Journal article
Published: 29 December 2020 in Antioxidants
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Polyphenols are considered protective against diseases associated with oxidative stress. Short-term intake of an anthocyanin-rich fruit juice resulted in significantly reduced deoxyribonucleic acid (DNA) strand-breaks in peripheral blood lymphocytes (PBLs) and affected antioxidant markers in healthy volunteers. Consequently, effects of long-term consumption of fruit juice are of particular interest. In focus was the impact on nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), the Nrf2-regulated genes NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) as well as effects on the gut microbiota. In a nine-week placebo-controlled intervention trial with 57 healthy male volunteers, consumption of anthocyanin-rich juice significantly increased NQO-1 and HO-1 transcript levels in PBLs compared to a placebo beverage as measured by real-time polymerase chain reaction (PCR). Three Nrf2-promotor single nucleotide polymorphisms (SNPs), analyzed by pyrosequencing, indicated an association between individual Nrf2 transcript levels and genotype. Moreover, the Nrf2 genotype appeared to correlate with the presence of specific microbial organisms identified by 16S-PCR and classified as Spirochaetaceae. Furthermore, the microbial community was significantly affected by the duration of juice consumption and intake of juice itself. Taken together, long-term consumption of anthocyanin-rich fruit juice affected Nrf2-dependent transcription in PBLs, indicating systemic effects. Individual Nrf2 genotypes may influence the antioxidant response, thus requiring consideration in future intervention studies focusing on the Nrf2 pathway. Anthocyanin-rich fruit juice had an extensive impact on the gut microbiota.

ACS Style

Isabel Anna Maria Groh; Alessandra Riva; Dominik Braun; Heidi G. Sutherland; Owen Williams; Tamara Bakuradze; Gudrun Pahlke; Elke Richling; Larisa M. Haupt; Lyn R. Griffiths; David Berry; Doris Marko. Long-Term Consumption of Anthocyanin-Rich Fruit Juice: Impact on Gut Microbiota and Antioxidant Markers in Lymphocytes of Healthy Males. Antioxidants 2020, 10, 27 .

AMA Style

Isabel Anna Maria Groh, Alessandra Riva, Dominik Braun, Heidi G. Sutherland, Owen Williams, Tamara Bakuradze, Gudrun Pahlke, Elke Richling, Larisa M. Haupt, Lyn R. Griffiths, David Berry, Doris Marko. Long-Term Consumption of Anthocyanin-Rich Fruit Juice: Impact on Gut Microbiota and Antioxidant Markers in Lymphocytes of Healthy Males. Antioxidants. 2020; 10 (1):27.

Chicago/Turabian Style

Isabel Anna Maria Groh; Alessandra Riva; Dominik Braun; Heidi G. Sutherland; Owen Williams; Tamara Bakuradze; Gudrun Pahlke; Elke Richling; Larisa M. Haupt; Lyn R. Griffiths; David Berry; Doris Marko. 2020. "Long-Term Consumption of Anthocyanin-Rich Fruit Juice: Impact on Gut Microbiota and Antioxidant Markers in Lymphocytes of Healthy Males." Antioxidants 10, no. 1: 27.

Research article
Published: 09 December 2020 in Molecular Nutrition & Food Research
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Scope Several studies suggest that regular coffee consumption may help preventing chronic diseases, but the impact of daily intake and the contribution of coffee metabolites in disease prevention are still unclear. The present study aimed at evaluating whether and how different patterns of coffee intake (one cup of espresso coffee/day, three cups of espresso coffee/day, one cup of espresso coffee/day and two cocoa‐based products containing coffee two times per day) might impact endogenous molecular pathways. Methods and Results A three‐arm, randomized, cross‐over trial was performed in 21 healthy volunteers who consumed each treatment for one month. Urine samples were collected to perform untargeted metabolomics based on UHPLC‐IMS‐HRMS. A total of 153 discriminant metabolites were identified. Several molecular features were associated with coffee consumption, while others were linked with different metabolic pathways, such as phenylalanine, tyrosine, energy metabolism, steroid hormone biosynthesis and arginine biosynthesis and metabolism. Conclusion This information has provided new insights into the metabolic routes by which coffee and coffee‐related metabolites may exert effects on human health. This article is protected by copyright. All rights reserved

ACS Style

Claudia Favari; Laura Righetti; Michele Tassotti; Lee Andrew Gethings; Daniela Martini; Alice Rosi; Monica Antonini; Josep Rubert; Claudine Manach; Alessandra Dei Cas; Riccardo Bonadonna; Furio Brighenti; Chiara Dall'asta; Pedro Mena; Daniele Del Rio. Metabolomic Changes after Coffee Consumption: New Paths on the Block. Molecular Nutrition & Food Research 2020, 65, e2000875 .

AMA Style

Claudia Favari, Laura Righetti, Michele Tassotti, Lee Andrew Gethings, Daniela Martini, Alice Rosi, Monica Antonini, Josep Rubert, Claudine Manach, Alessandra Dei Cas, Riccardo Bonadonna, Furio Brighenti, Chiara Dall'asta, Pedro Mena, Daniele Del Rio. Metabolomic Changes after Coffee Consumption: New Paths on the Block. Molecular Nutrition & Food Research. 2020; 65 (3):e2000875.

Chicago/Turabian Style

Claudia Favari; Laura Righetti; Michele Tassotti; Lee Andrew Gethings; Daniela Martini; Alice Rosi; Monica Antonini; Josep Rubert; Claudine Manach; Alessandra Dei Cas; Riccardo Bonadonna; Furio Brighenti; Chiara Dall'asta; Pedro Mena; Daniele Del Rio. 2020. "Metabolomic Changes after Coffee Consumption: New Paths on the Block." Molecular Nutrition & Food Research 65, no. 3: e2000875.

Journal article
Published: 13 October 2020 in Foods
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In the present work, the provenance discrimination of Argentinian honeys was used as case study to compare the capabilities of three spectroscopic techniques as fast screening platforms for honey authentication purposes. Multifloral honeys were collected among three main honey-producing regions of Argentina over four harvesting seasons. Each sample was fingerprinted by FT-MIR, NIR and FT-Raman spectroscopy. The spectroscopic platforms were compared on the basis of the classification performance achieved under a supervised chemometric approach. Furthermore, low- mid- and high-level data fusion were attempted in order to enhance the classification results. Finally, the best-performing solution underwent to SIMCA modelling with the purpose of reproducing a food authentication scenario. All the developed classification models underwent to a “year-by-year” validation strategy, enabling a sound assessment of their long-term robustness and excluding any issue of model overfitting. Excellent classification scores were achieved by all the technologies and nearly perfect classification was provided by FT-MIR. All the data fusion strategies provided satisfying outcomes, with the mid- and high-level approaches outperforming the low-level data fusion. However, no significant advantage over the FT-MIR alone was obtained. SIMCA modelling of FT-MIR data produced highly sensitive and specific models and an overall prediction ability improvement was achieved when more harvesting seasons were used for the model calibration (86.7% sensitivity and 91.1% specificity). The results obtained in the present work suggested the major potential of FT-MIR for fingerprinting-based honey authentication and demonstrated that accuracy levels that may be commercially useful can be reached. On the other hand, the combination of multiple vibrational spectroscopic fingerprints represents a choice that should be carefully evaluated from a cost/benefit standpoint within the industrial context.

ACS Style

Tito Damiani; Rosa M. Alonso-Salces; Inés Aubone; Vincent Baeten; Quentin Arnould; Chiara Dall’Asta; Sandra R. Fuselli; Juan Antonio Fernández Pierna. Vibrational Spectroscopy Coupled to a Multivariate Analysis Tiered Approach for Argentinean Honey Provenance Confirmation. Foods 2020, 9, 1450 .

AMA Style

Tito Damiani, Rosa M. Alonso-Salces, Inés Aubone, Vincent Baeten, Quentin Arnould, Chiara Dall’Asta, Sandra R. Fuselli, Juan Antonio Fernández Pierna. Vibrational Spectroscopy Coupled to a Multivariate Analysis Tiered Approach for Argentinean Honey Provenance Confirmation. Foods. 2020; 9 (10):1450.

Chicago/Turabian Style

Tito Damiani; Rosa M. Alonso-Salces; Inés Aubone; Vincent Baeten; Quentin Arnould; Chiara Dall’Asta; Sandra R. Fuselli; Juan Antonio Fernández Pierna. 2020. "Vibrational Spectroscopy Coupled to a Multivariate Analysis Tiered Approach for Argentinean Honey Provenance Confirmation." Foods 9, no. 10: 1450.

Original paper
Published: 09 October 2020 in European Food Research and Technology
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In the present study, we have characterized for the first time the volatile fraction of 20 pomegranate juices from fruits harvested in Northern Italy and southern Montenegro, by means of headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography–mass spectrometry technique (GC–MS). The volatile profile accounted for 57 compounds belonging mainly to three chemical classes: alcohols, aldehydes and terpenes. Thanks to advance chemometric analysis, the samples were clusterized according to the geographical origin, and the volatiles responsible for differentiation were identified, indicating that the use of volatile profile for discriminating between pomegranate ecotypes grown in different geographical areas is a promising approach. Overall, the chemical information acquired represents a very relevant tool for the retrieval and exploitation of minor varieties and in support of biodiversity of these promising geographical areas for pomegranate cultivation.

ACS Style

Deborah Beghè; Martina Cirlini; Elisa Beneventi; Čizmović Miroslav; Perović Tatjana; Tommaso Ganino; Raffaella Petruccelli; Chiara Dall’Asta. Volatile profile of Italian and Montenegrine pomegranate juices for geographical origin classification. European Food Research and Technology 2020, 247, 211 -220.

AMA Style

Deborah Beghè, Martina Cirlini, Elisa Beneventi, Čizmović Miroslav, Perović Tatjana, Tommaso Ganino, Raffaella Petruccelli, Chiara Dall’Asta. Volatile profile of Italian and Montenegrine pomegranate juices for geographical origin classification. European Food Research and Technology. 2020; 247 (1):211-220.

Chicago/Turabian Style

Deborah Beghè; Martina Cirlini; Elisa Beneventi; Čizmović Miroslav; Perović Tatjana; Tommaso Ganino; Raffaella Petruccelli; Chiara Dall’Asta. 2020. "Volatile profile of Italian and Montenegrine pomegranate juices for geographical origin classification." European Food Research and Technology 247, no. 1: 211-220.

Journal article
Published: 28 September 2020 in Food and Chemical Toxicology
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In the past, it was generally accepted as a default assumption that No-Observed-Adverse-Effect Levels (NOAELs) or Lowest-Observed-Adverse-Effect Levels (LOAELs) in long-term toxicity studies are lower than in short-term ones, i.e. the toxic potency increases with prolonged exposure duration. Recent studies on pesticides and industrial chemicals reported that subacute, subchronic or chronic NOAELs/LOAELs are similar when study design factors are appropriately considered. We investigated whether these findings also apply to certain food constituents. After reviewing subchronic and chronic toxicity studies on more than 100 compounds, a total of 32 compounds could be included in the analysis. Geometric mean (GM) values of subchronic vs. chronic NOAEL or LOAEL ratios ranged from 1.0 to 2.0, with a geometric standard deviation from 2.2 to 4.2, which is consistent with data reported in the literature. While for many of the investigated compounds the ratio is around 1 – suggesting that health-based guidance values could appropriately be derived from subchronic toxicity studies – our study also identified some substances with higher ratios leading to a GM of around 2. The EFSA Scientific Committee suggested to apply an uncertainty factor of 2 to extrapolate from subchronic to chronic studies and, as a precautionary approach, we concur with this suggestion.

ACS Style

Sabine Guth; Angelika Roth; Barbara Engeli; Dirk W. Lachenmeier; Alexander T. Cartus; Stephanie Hüser; Matthias Baum; Patrick Diel; Gerhard Eisenbrand; Jan G. Hengstler; Hans-Ulrich Humpf; Hans-Georg Joost; Alfonso Lampen; Marcel Leist; Doris Marko; Pablo Steinberg; Angela Mally; Jürg A. Zarn. Comparison of points of departure between subchronic and chronic toxicity studies on food additives, food contaminants and natural food constituents. Food and Chemical Toxicology 2020, 146, 111784 .

AMA Style

Sabine Guth, Angelika Roth, Barbara Engeli, Dirk W. Lachenmeier, Alexander T. Cartus, Stephanie Hüser, Matthias Baum, Patrick Diel, Gerhard Eisenbrand, Jan G. Hengstler, Hans-Ulrich Humpf, Hans-Georg Joost, Alfonso Lampen, Marcel Leist, Doris Marko, Pablo Steinberg, Angela Mally, Jürg A. Zarn. Comparison of points of departure between subchronic and chronic toxicity studies on food additives, food contaminants and natural food constituents. Food and Chemical Toxicology. 2020; 146 ():111784.

Chicago/Turabian Style

Sabine Guth; Angelika Roth; Barbara Engeli; Dirk W. Lachenmeier; Alexander T. Cartus; Stephanie Hüser; Matthias Baum; Patrick Diel; Gerhard Eisenbrand; Jan G. Hengstler; Hans-Ulrich Humpf; Hans-Georg Joost; Alfonso Lampen; Marcel Leist; Doris Marko; Pablo Steinberg; Angela Mally; Jürg A. Zarn. 2020. "Comparison of points of departure between subchronic and chronic toxicity studies on food additives, food contaminants and natural food constituents." Food and Chemical Toxicology 146, no. : 111784.

Journal article
Published: 12 September 2020 in Applied Sciences
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Emodin, a widespread natural anthraquinone, has many biological activities including health-protective and adverse effects. Amongst beneficial effects, potential antiviral activity against coronavirus responsible for the severe acute respiratory syndrome outbreak in 2002–2003 has been described associated with the inhibition of the host cells target receptors recognition by the viral Spike protein. However, the inhibition mechanisms have not been fully characterized, hindering the rational use of emodin as a model compound to develop more effective analogues. This work investigates emodin interaction with the Spike protein to provide a mechanistic explanation of such inhibition. A 3D molecular modeling approach consisting of docking simulations, pharmacophoric analysis and molecular dynamics was used. The plausible mechanism is described as an interaction of emodin at the protein–protein interface which destabilizes the viral protein-target receptor complex. This analysis has been extended to the Spike protein of the coronavirus responsible for the current pandemic hypothesizing emodin’s functional conservation. This solid knowledge-based foothold provides a possible mechanistic rationale of the antiviral activity of emodin as a future basis for the potential development of efficient antiviral cognate compounds. Data gaps and future work on emodin-related adverse effects in parallel to its antiviral pharmacology are explored.

ACS Style

Luca Dellafiora; Jean Lou C M Dorne; Gianni Galaverna; Chiara Dall’Asta. Preventing the Interaction between Coronaviruses Spike Protein and Angiotensin I Converting Enzyme 2: An In Silico Mechanistic Case Study on Emodin as a Potential Model Compound. Applied Sciences 2020, 10, 6358 .

AMA Style

Luca Dellafiora, Jean Lou C M Dorne, Gianni Galaverna, Chiara Dall’Asta. Preventing the Interaction between Coronaviruses Spike Protein and Angiotensin I Converting Enzyme 2: An In Silico Mechanistic Case Study on Emodin as a Potential Model Compound. Applied Sciences. 2020; 10 (18):6358.

Chicago/Turabian Style

Luca Dellafiora; Jean Lou C M Dorne; Gianni Galaverna; Chiara Dall’Asta. 2020. "Preventing the Interaction between Coronaviruses Spike Protein and Angiotensin I Converting Enzyme 2: An In Silico Mechanistic Case Study on Emodin as a Potential Model Compound." Applied Sciences 10, no. 18: 6358.

Original article
Published: 14 August 2020 in Mycotoxin Research
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Alternaria molds produce a variety of chemically diverse secondary metabolites with potentially adverse effects on human health. However, data on occurrence in food and human exposure is inconsistent for some of these mycotoxins. Membrane filtration is a frequent step in many sample preparation procedures for LC-MS-based methods analyzing food contaminants. Yet, little is known about the possibility of adsorptive phenomena that might result in analyte losses. Thus, we treated a complex extract of Alternaria toxins with several types of syringe filters and unraveled the impact on its chemical composition by LC-MS/MS. We observed significant, and in some cases complete, losses of compounds due to filtration. Particularly, two key Alternaria toxins, alternariol (AOH) and its monomethyl ether (AME), were heavily affected. As a comparison with published food surveys indicating a correlation of the type of filtration used with lower incidence reports in food, our results point at a possible underestimation of AME in past exposure assessment. Also, perylene quinones were greatly affected by filtration, underlining the importance to take this into consideration during analytical method development. Furthermore, we applied the comet assay in HT-29 cells to elucidate the impact of filtration on the genotoxicity of the extract. We observed strong coincidences with the loss of epoxide-carrying metabolites and also an intriguing induction of oxidative DNA damage by yet toxicologically uncharacterized Alternaria toxins. In conclusion, we highlight potential issues with sample filtration and call for a critical re-evaluation of previous food occurrence data in the light of the results at hand.

ACS Style

Georg Aichinger; Natálie Živná; Elisabeth Varga; Francesco Crudo; Benedikt Warth; Doris Marko. Microfiltration results in the loss of analytes and affects the in vitro genotoxicity of a complex mixture of Alternaria toxins. Mycotoxin Research 2020, 36, 399 -408.

AMA Style

Georg Aichinger, Natálie Živná, Elisabeth Varga, Francesco Crudo, Benedikt Warth, Doris Marko. Microfiltration results in the loss of analytes and affects the in vitro genotoxicity of a complex mixture of Alternaria toxins. Mycotoxin Research. 2020; 36 (4):399-408.

Chicago/Turabian Style

Georg Aichinger; Natálie Živná; Elisabeth Varga; Francesco Crudo; Benedikt Warth; Doris Marko. 2020. "Microfiltration results in the loss of analytes and affects the in vitro genotoxicity of a complex mixture of Alternaria toxins." Mycotoxin Research 36, no. 4: 399-408.

Original research article
Published: 06 August 2020 in Frontiers in Nutrition
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Butenolide (BUT, 4-acetamido-4-hydroxy-2-butenoic acid gamma-lactone) is a secondary metabolite produced by several Fusarium species and is co-produced with the major trichothecene mycotoxin deoxynivalenol (DON) on cereal grains throughout the world. BUT has low acute toxicity and only very limited occurrence and exposure data are available. The intestinal epithelium represents the first physiological barrier against food contaminants. We aimed to elucidate the intestinal inflammatory response of the human, non-cancer epithelial HCEC-1CT cells to BUT and to characterize potential combinatory interactions with co-occurring trichothecenes, such as DON and NX-3. Using a reporter gene approach, BUT (≥5 μM, 20 h) was found to decrease lipopolysaccharide (LPS; 10 ng/mL) induced nuclear factor kappa B (NF-κB) activation in a dose-dependent manner, and in combinatory treatments BUT represses trichothecene-induced enhancement of this important inflammatory pathway. Analysis of transcription and secretion levels of NF-κB-dependent, pro-inflammatory cytokines, revealed a significant down-regulation of IL-1β, IL-6, and TNF-α in IL-1β-stimulated (25 ng/mL) HCEC-1CT cells after BUT exposure (10 μM). Trichothecene-induced expression of pro-inflammatory cytokines by the presence of 1 μM DON or NX-3 was substantially suppressed in the presence of 10 μM BUT. The emerging mycotoxin BUT has the ability to suppress NF-κB-induced intestinal inflammatory response mechanisms and to modulate substantially the immune responsiveness of HCEC-1CT cells after trichothecene treatment. Our results suggest that BUT, present in naturally occurring mixtures of Fusarium fungal metabolites, should be increasingly monitored, and the mechanism of inhibition of NF-κB that might affect the pathogenesis or progression of intestinal inflammatory disorders, should be further investigated.

ACS Style

Lydia Woelflingseder; Gerhard Adam; Doris Marko. Suppression of Trichothecene-Mediated Immune Response by the Fusarium Secondary Metabolite Butenolide in Human Colon Epithelial Cells. Frontiers in Nutrition 2020, 7, 127 .

AMA Style

Lydia Woelflingseder, Gerhard Adam, Doris Marko. Suppression of Trichothecene-Mediated Immune Response by the Fusarium Secondary Metabolite Butenolide in Human Colon Epithelial Cells. Frontiers in Nutrition. 2020; 7 ():127.

Chicago/Turabian Style

Lydia Woelflingseder; Gerhard Adam; Doris Marko. 2020. "Suppression of Trichothecene-Mediated Immune Response by the Fusarium Secondary Metabolite Butenolide in Human Colon Epithelial Cells." Frontiers in Nutrition 7, no. : 127.

Journal article
Published: 09 July 2020 in Biomolecules
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Alternaria molds simultaneously produce a large variety of mycotoxins, of which several were previously reported to induce enzymes of phase I metabolism through aryl hydrocarbon receptor activation. Thus, we investigated the potential of naturally occurring Alternaria toxin mixtures to induce Cytochrome P450 (CYP) 1A1/1A2/1B1 activity. Two variants of an extract from cultured Alternaria alternata, as well as the toxins alternariol (AOH), alternariol monomethyl ether (AME), altertoxin I (ATX-I), and altertoxin II (ATX-II), were tested singularly and in binary mixtures applying the 7-ethoxy-resorufin-O-deethylase (EROD) assay in MCF-7 breast cancer cells. Sub-cytotoxic concentrations of the two toxin mixtures, as well as ATX-I, ATX-II and AOH, exhibited dose-dependent enhancements of CYP 1 activity. ATX-I and ATX-II interacted synergistically in this respect, demonstrating the two perylene quinones as major contributors to the extract’s potential. Binary mixtures between AOH and the two altertoxins respectively exhibited concentration-dependent antagonistic as well as synergistic combinatory effects. Notably, AME showed no efficacy towards EROD enzyme activity or impact on other toxins’ efficacy. Hence, this study provides insights into synergistic and other combinatory effects of Alternaria toxins in natural co-occurrence scenarios in the context of AhR signalling pathway activation in breast cancer cells.

ACS Style

Julia Hohenbichler; Georg Aichinger; Michael Rychlik; Giorgia Del Favero; Doris Marko. Alternaria alternata Toxins Synergistically Activate the Aryl Hydrocarbon Receptor Pathway In Vitro. Biomolecules 2020, 10, 1018 .

AMA Style

Julia Hohenbichler, Georg Aichinger, Michael Rychlik, Giorgia Del Favero, Doris Marko. Alternaria alternata Toxins Synergistically Activate the Aryl Hydrocarbon Receptor Pathway In Vitro. Biomolecules. 2020; 10 (7):1018.

Chicago/Turabian Style

Julia Hohenbichler; Georg Aichinger; Michael Rychlik; Giorgia Del Favero; Doris Marko. 2020. "Alternaria alternata Toxins Synergistically Activate the Aryl Hydrocarbon Receptor Pathway In Vitro." Biomolecules 10, no. 7: 1018.