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

Alternaria mycotoxins Chemical mixture Food contaminants In vitro toxicity

Journal

Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615

Informations de publication

Date de publication:
02 Oct 2024
Historique:
received: 26 06 2024
accepted: 19 09 2024
medline: 3 10 2024
pubmed: 3 10 2024
entrez: 2 10 2024
Statut: aheadofprint

Résumé

Alternaria mycotoxins may pose significant challenges to food safety and public health due to the wide spectrum of reported adverse effects. Despite this, critical information on the immunomodulatory and antiestrogenic properties of most of these contaminants is still lacking. The present study aimed to identify the mycotoxins responsible for the immunosuppressive and antiestrogenic effects of a complex extract of Alternaria mycotoxins (CE) obtained by growing an Alternaria alternata strain on rice. Through a toxicity-guided fractionation procedure involving the production of CE-fractions by supercritical fluid chromatography and mycotoxin quantification by LC-MS/MS, the mycotoxins alternariol (AOH), tenuazonic acid (TeA), altertoxin I (ATX-I), and alterperylenol (ALTP) were identified as potential toxicologically relevant constituents contributing to the in vitro effects exerted by the extract. The assessment of the immunomodulatory effects, performed by applying the NF-κB reporter gene assay in THP1-Lucia™ monocytes, revealed the scarce contribution of AOH to the effects exerted by the CE. TeA showed no effect on the NF-κB pathway up to 250 µM, whereas ATX-I and ALTP suppressed the LPS-mediated pathway activation at concentrations ≥ 1 µM. The evaluation of antiestrogenic effects, performed in Ishikawa cells by applying the alkaline phosphatase assay, revealed the ability of ALTP (≥ 0.4 µM) and ATX-I (≥ 2 µM) to suppress the estrogen-dependent expression of enzyme activity. Given the risk of detrimental impacts stemming from alterations in endocrine and systemic immune responses by the investigated mycotoxins, further studies are needed to elucidate their underlying mechanisms of action and comprehensively evaluate the health risks posed by these toxins.

Identifiants

DOI: 10.1007/s00204-024-03877-1 PMID: 39358629
pubmed: 39358629
doi: 10.1007/s00204-024-03877-1
pii: 10.1007/s00204-024-03877-1
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Horizon Europe Research and Innovation Programme
ID : 101057014

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Francesco Crudo (F)

Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Str. 38, 1090, Vienna, Austria.

Vanessa Partsch (V)

Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Str. 38, 1090, Vienna, Austria.
Doctoral School in Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria.

Dennis Braga (D)

Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Str. 38, 1090, Vienna, Austria.

Ruzica Blažević (R)

Division of Pharmacognosy, Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria.

Judith M Rollinger (JM)

Division of Pharmacognosy, Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria.

Elisabeth Varga (E)

Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Str. 38, 1090, Vienna, Austria.
Unit Food Hygiene and Technology, Centre for Food Science and Veterinary Public Health, Clinical Department for Farm Animals and Food System Science, University of Veterinary Medicine, Vienna, Vienna, Austria.

Doris Marko (D)

Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Str. 38, 1090, Vienna, Austria. doris.marko@univie.ac.at.
ORCID: 0000-0001-6568-2944

Classifications MeSH