Combined Cytotoxic Effects of the Fungicide Azoxystrobin and Common Food-Contaminating Mycotoxins

This study assessed the cytotoxicity of the individual and combined exposure to the fungicide azoxystrobin (AZX) and the three common mycotoxins found in food: ochratoxin A (OTA), deoxynivalenol (DON), and T-2 toxin. Cytotoxic effects were evaluated using the resazurin and MTT assays in human hepato...

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Main Authors: Cristina Fuentes, Veronica Zingales, José Manuel Barat, María-José Ruiz
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Foods
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Online Access:https://www.mdpi.com/2304-8158/14/7/1226
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author Cristina Fuentes
Veronica Zingales
José Manuel Barat
María-José Ruiz
author_facet Cristina Fuentes
Veronica Zingales
José Manuel Barat
María-José Ruiz
author_sort Cristina Fuentes
collection DOAJ
description This study assessed the cytotoxicity of the individual and combined exposure to the fungicide azoxystrobin (AZX) and the three common mycotoxins found in food: ochratoxin A (OTA), deoxynivalenol (DON), and T-2 toxin. Cytotoxic effects were evaluated using the resazurin and MTT assays in human hepatocarcinoma (HepG2) cells after 24 h of exposure, and the type of interaction between the compounds was determined using the isobologram method. Results showed that T-2 was the most cytotoxic compound, followed by DON, OTA, and AZX. The compound ratios in the mixture were calculated using three sublethal concentrations (IC<sub>50/2</sub>, IC<sub>50/4</sub>, and IC<sub>50/8</sub>) to achieve equal toxicity for each compound. Interaction analysis revealed that the nature of the interaction varied across components and concentrations. The AZX and DON mixture produced an antagonistic effect at all the analyzed effect levels. AZX and OTA or T2 mixtures, and tertiary combinations displayed antagonism at low effect values but additivity at high effect levels. Importantly, the quaternary mixture demonstrated synergism at all the effect levels. These findings highlight that the co-occurrence of fungicides and mycotoxins in food commodities can lead to complex exposure scenarios that may result in combined toxic effects on the organism.
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spelling doaj-art-7ab3a0146b9e48ff85991012d1d8f9762025-08-20T02:15:58ZengMDPI AGFoods2304-81582025-03-01147122610.3390/foods14071226Combined Cytotoxic Effects of the Fungicide Azoxystrobin and Common Food-Contaminating MycotoxinsCristina Fuentes0Veronica Zingales1José Manuel Barat2María-José Ruiz3University Institute of Food Engineering–FoodUPV, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, SpainResearch Group in Alternative Methods for Determining Toxics Effects and Risk Assessment of Contaminants and Mixtures (RiskTox), Universitat de València, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, SpainUniversity Institute of Food Engineering–FoodUPV, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia, SpainResearch Group in Alternative Methods for Determining Toxics Effects and Risk Assessment of Contaminants and Mixtures (RiskTox), Universitat de València, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, SpainThis study assessed the cytotoxicity of the individual and combined exposure to the fungicide azoxystrobin (AZX) and the three common mycotoxins found in food: ochratoxin A (OTA), deoxynivalenol (DON), and T-2 toxin. Cytotoxic effects were evaluated using the resazurin and MTT assays in human hepatocarcinoma (HepG2) cells after 24 h of exposure, and the type of interaction between the compounds was determined using the isobologram method. Results showed that T-2 was the most cytotoxic compound, followed by DON, OTA, and AZX. The compound ratios in the mixture were calculated using three sublethal concentrations (IC<sub>50/2</sub>, IC<sub>50/4</sub>, and IC<sub>50/8</sub>) to achieve equal toxicity for each compound. Interaction analysis revealed that the nature of the interaction varied across components and concentrations. The AZX and DON mixture produced an antagonistic effect at all the analyzed effect levels. AZX and OTA or T2 mixtures, and tertiary combinations displayed antagonism at low effect values but additivity at high effect levels. Importantly, the quaternary mixture demonstrated synergism at all the effect levels. These findings highlight that the co-occurrence of fungicides and mycotoxins in food commodities can lead to complex exposure scenarios that may result in combined toxic effects on the organism.https://www.mdpi.com/2304-8158/14/7/1226fungicidemycotoxinschemical mixturesinteractionHepG2 cells
spellingShingle Cristina Fuentes
Veronica Zingales
José Manuel Barat
María-José Ruiz
Combined Cytotoxic Effects of the Fungicide Azoxystrobin and Common Food-Contaminating Mycotoxins
Foods
fungicide
mycotoxins
chemical mixtures
interaction
HepG2 cells
title Combined Cytotoxic Effects of the Fungicide Azoxystrobin and Common Food-Contaminating Mycotoxins
title_full Combined Cytotoxic Effects of the Fungicide Azoxystrobin and Common Food-Contaminating Mycotoxins
title_fullStr Combined Cytotoxic Effects of the Fungicide Azoxystrobin and Common Food-Contaminating Mycotoxins
title_full_unstemmed Combined Cytotoxic Effects of the Fungicide Azoxystrobin and Common Food-Contaminating Mycotoxins
title_short Combined Cytotoxic Effects of the Fungicide Azoxystrobin and Common Food-Contaminating Mycotoxins
title_sort combined cytotoxic effects of the fungicide azoxystrobin and common food contaminating mycotoxins
topic fungicide
mycotoxins
chemical mixtures
interaction
HepG2 cells
url https://www.mdpi.com/2304-8158/14/7/1226
work_keys_str_mv AT cristinafuentes combinedcytotoxiceffectsofthefungicideazoxystrobinandcommonfoodcontaminatingmycotoxins
AT veronicazingales combinedcytotoxiceffectsofthefungicideazoxystrobinandcommonfoodcontaminatingmycotoxins
AT josemanuelbarat combinedcytotoxiceffectsofthefungicideazoxystrobinandcommonfoodcontaminatingmycotoxins
AT mariajoseruiz combinedcytotoxiceffectsofthefungicideazoxystrobinandcommonfoodcontaminatingmycotoxins