Discovery of the Alternaria mycotoxins alterperylenol and altertoxin I as novel immunosuppressive and antiestrogenic compounds in vitro

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Autores principales: Crudo, Francesco, Partsch, Vanessa, Braga, Dennis, Blažević, Ruzica, Rollinger, Judith, Varga, Elisabeth, Marko, Doris
Formato: Recurso digital
Lenguaje:inglés
Publicado: Zenodo 2024
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author Crudo, Francesco
Partsch, Vanessa
Braga, Dennis
Blažević, Ruzica
Rollinger, Judith
Varga, Elisabeth
Marko, Doris
author_facet Crudo, Francesco
Partsch, Vanessa
Braga, Dennis
Blažević, Ruzica
Rollinger, Judith
Varga, Elisabeth
Marko, Doris
contents <p>Alternaria mycotoxins may pose signifcant challenges to food safety and public health due to the wide spectrum of reported<br>adverse efects. Despite this, critical information on the immunomodulatory and antiestrogenic properties of most of these<br>contaminants is still lacking. The present study aimed to identify the mycotoxins responsible for the immunosuppressive<br>and antiestrogenic efects of a complex extract of Alternaria mycotoxins (CE) obtained by growing an Alternaria alternata<br>strain on rice. Through a toxicity-guided fractionation procedure involving the production of CE-fractions by supercritical<br>fuid chromatography and mycotoxin quantifcation by LC–MS/MS, the mycotoxins alternariol (AOH), tenuazonic acid<br>(TeA), altertoxin I (ATX-I), and alterperylenol (ALTP) were identifed as potential toxicologically relevant constituents<br>contributing to the in vitro efects exerted by the extract. The assessment of the immunomodulatory efects, performed by<br>applying the NF-κB reporter gene assay in THP1-Lucia™ monocytes, revealed the scarce contribution of AOH to the efects<br>exerted by the CE. TeA showed no efect on the NF-κB pathway up to 250 µM, whereas ATX-I and ALTP suppressed the<br>LPS-mediated pathway activation at concentrations≥1 µM. The evaluation of antiestrogenic efects, performed in Ishikawa<br>cells by applying the alkaline phosphatase assay, revealed the ability of ALTP (≥0.4 µM) and ATX-I (≥2 µM) to suppress<br>the estrogen-dependent expression of enzyme activity. Given the risk of detrimental impacts stemming from alterations<br>in endocrine and systemic immune responses by the investigated mycotoxins, further studies are needed to elucidate their<br>underlying mechanisms of action and comprehensively evaluate the health risks posed by these toxins.</p>
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publishDate 2024
publisher Zenodo
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spellingShingle Discovery of the Alternaria mycotoxins alterperylenol and altertoxin I as novel immunosuppressive and antiestrogenic compounds in vitro
Crudo, Francesco
Partsch, Vanessa
Braga, Dennis
Blažević, Ruzica
Rollinger, Judith
Varga, Elisabeth
Marko, Doris
In vitro toxicity
chemical mixtures
food contaminants
Alternaria mycotoxins
<p>Alternaria mycotoxins may pose signifcant challenges to food safety and public health due to the wide spectrum of reported<br>adverse efects. Despite this, critical information on the immunomodulatory and antiestrogenic properties of most of these<br>contaminants is still lacking. The present study aimed to identify the mycotoxins responsible for the immunosuppressive<br>and antiestrogenic efects of a complex extract of Alternaria mycotoxins (CE) obtained by growing an Alternaria alternata<br>strain on rice. Through a toxicity-guided fractionation procedure involving the production of CE-fractions by supercritical<br>fuid chromatography and mycotoxin quantifcation by LC–MS/MS, the mycotoxins alternariol (AOH), tenuazonic acid<br>(TeA), altertoxin I (ATX-I), and alterperylenol (ALTP) were identifed as potential toxicologically relevant constituents<br>contributing to the in vitro efects exerted by the extract. The assessment of the immunomodulatory efects, performed by<br>applying the NF-κB reporter gene assay in THP1-Lucia™ monocytes, revealed the scarce contribution of AOH to the efects<br>exerted by the CE. TeA showed no efect on the NF-κB pathway up to 250 µM, whereas ATX-I and ALTP suppressed the<br>LPS-mediated pathway activation at concentrations≥1 µM. The evaluation of antiestrogenic efects, performed in Ishikawa<br>cells by applying the alkaline phosphatase assay, revealed the ability of ALTP (≥0.4 µM) and ATX-I (≥2 µM) to suppress<br>the estrogen-dependent expression of enzyme activity. Given the risk of detrimental impacts stemming from alterations<br>in endocrine and systemic immune responses by the investigated mycotoxins, further studies are needed to elucidate their<br>underlying mechanisms of action and comprehensively evaluate the health risks posed by these toxins.</p>
title Discovery of the Alternaria mycotoxins alterperylenol and altertoxin I as novel immunosuppressive and antiestrogenic compounds in vitro
topic In vitro toxicity
chemical mixtures
food contaminants
Alternaria mycotoxins
url https://doi.org/10.1007/s00204-024-03877-1