A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin a in human intestinal cells

Ricardo Assunção, Mariana Pinhão, Susana Loureiro, P. Alvito, Maria João Silva

Research output: Contribution to journalArticle

Abstract

Humans can be exposed to a complex and variable combination of mycotoxins. After ingestion, intestinal mucosa constitutes the first biological barrier that can be exposed to high concentrations of these toxins. The present study aimed to characterize the combined cytotoxicity, genotoxicity and impact on the gastrointestinal barrier integrity of patulin (PAT, 0.7 μM to 100 μM) and ochratoxin A (OTA, 1 μM to 200 μM) mixtures in Caco-2 cells. A dose-ratio deviation was verified for cytotoxicity, implying that OTA was mainly responsible for synergism when dominant in the mixture, while this pattern was changed to antagonism for the highest PAT concentrations. Genotoxicity (comet assay) results were compatible with an interactive DNA damaging effect at the highest PAT and OTA concentrations, not clearly mediated by the formation of oxidative DNA breaks. Regarding gastrointestinal barrier integrity, a potential synergism was attained at low levels of both mycotoxins, changing to antagonism at higher doses. The present results indicate that combined mycotoxins effects may arise at the intestinal level and should not be underestimated when evaluating their risk to human health.

Original languageEnglish
Pages (from-to)120-129
Number of pages10
JournalToxicology Letters
Volume313
DOIs
Publication statusPublished - 1 Oct 2019

Fingerprint

Patulin
Ochratoxins
Mycotoxins
Poisons
Cytotoxicity
DNA Breaks
Comet Assay
Caco-2 Cells
DNA
Intestinal Mucosa
Assays
Eating
Health

Keywords

  • Barrier integrity
  • Cytotoxicity
  • Gastrointestinal toxicity
  • Genotoxicity
  • Interaction effects
  • Mycotoxin mixtures

Cite this

Assunção, Ricardo ; Pinhão, Mariana ; Loureiro, Susana ; Alvito, P. ; Silva, Maria João. / A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin a in human intestinal cells. In: Toxicology Letters. 2019 ; Vol. 313. pp. 120-129.
@article{d36576ba18fe4a2aad551fdc6a5f00c9,
title = "A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin a in human intestinal cells",
abstract = "Humans can be exposed to a complex and variable combination of mycotoxins. After ingestion, intestinal mucosa constitutes the first biological barrier that can be exposed to high concentrations of these toxins. The present study aimed to characterize the combined cytotoxicity, genotoxicity and impact on the gastrointestinal barrier integrity of patulin (PAT, 0.7 μM to 100 μM) and ochratoxin A (OTA, 1 μM to 200 μM) mixtures in Caco-2 cells. A dose-ratio deviation was verified for cytotoxicity, implying that OTA was mainly responsible for synergism when dominant in the mixture, while this pattern was changed to antagonism for the highest PAT concentrations. Genotoxicity (comet assay) results were compatible with an interactive DNA damaging effect at the highest PAT and OTA concentrations, not clearly mediated by the formation of oxidative DNA breaks. Regarding gastrointestinal barrier integrity, a potential synergism was attained at low levels of both mycotoxins, changing to antagonism at higher doses. The present results indicate that combined mycotoxins effects may arise at the intestinal level and should not be underestimated when evaluating their risk to human health.",
keywords = "Barrier integrity, Cytotoxicity, Gastrointestinal toxicity, Genotoxicity, Interaction effects, Mycotoxin mixtures",
author = "Ricardo Assun{\cc}{\~a}o and Mariana Pinh{\~a}o and Susana Loureiro and P. Alvito and Silva, {Maria Jo{\~a}o}",
year = "2019",
month = "10",
day = "1",
doi = "10.1016/j.toxlet.2019.06.002",
language = "English",
volume = "313",
pages = "120--129",
journal = "Toxicology Letters",
issn = "0378-4274",
publisher = "Elsevier Ireland Ltd.",

}

A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin a in human intestinal cells. / Assunção, Ricardo; Pinhão, Mariana; Loureiro, Susana; Alvito, P.; Silva, Maria João.

In: Toxicology Letters, Vol. 313, 01.10.2019, p. 120-129.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A multi-endpoint approach to the combined toxic effects of patulin and ochratoxin a in human intestinal cells

AU - Assunção, Ricardo

AU - Pinhão, Mariana

AU - Loureiro, Susana

AU - Alvito, P.

AU - Silva, Maria João

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Humans can be exposed to a complex and variable combination of mycotoxins. After ingestion, intestinal mucosa constitutes the first biological barrier that can be exposed to high concentrations of these toxins. The present study aimed to characterize the combined cytotoxicity, genotoxicity and impact on the gastrointestinal barrier integrity of patulin (PAT, 0.7 μM to 100 μM) and ochratoxin A (OTA, 1 μM to 200 μM) mixtures in Caco-2 cells. A dose-ratio deviation was verified for cytotoxicity, implying that OTA was mainly responsible for synergism when dominant in the mixture, while this pattern was changed to antagonism for the highest PAT concentrations. Genotoxicity (comet assay) results were compatible with an interactive DNA damaging effect at the highest PAT and OTA concentrations, not clearly mediated by the formation of oxidative DNA breaks. Regarding gastrointestinal barrier integrity, a potential synergism was attained at low levels of both mycotoxins, changing to antagonism at higher doses. The present results indicate that combined mycotoxins effects may arise at the intestinal level and should not be underestimated when evaluating their risk to human health.

AB - Humans can be exposed to a complex and variable combination of mycotoxins. After ingestion, intestinal mucosa constitutes the first biological barrier that can be exposed to high concentrations of these toxins. The present study aimed to characterize the combined cytotoxicity, genotoxicity and impact on the gastrointestinal barrier integrity of patulin (PAT, 0.7 μM to 100 μM) and ochratoxin A (OTA, 1 μM to 200 μM) mixtures in Caco-2 cells. A dose-ratio deviation was verified for cytotoxicity, implying that OTA was mainly responsible for synergism when dominant in the mixture, while this pattern was changed to antagonism for the highest PAT concentrations. Genotoxicity (comet assay) results were compatible with an interactive DNA damaging effect at the highest PAT and OTA concentrations, not clearly mediated by the formation of oxidative DNA breaks. Regarding gastrointestinal barrier integrity, a potential synergism was attained at low levels of both mycotoxins, changing to antagonism at higher doses. The present results indicate that combined mycotoxins effects may arise at the intestinal level and should not be underestimated when evaluating their risk to human health.

KW - Barrier integrity

KW - Cytotoxicity

KW - Gastrointestinal toxicity

KW - Genotoxicity

KW - Interaction effects

KW - Mycotoxin mixtures

UR - http://www.scopus.com/inward/record.url?scp=85068259787&partnerID=8YFLogxK

U2 - 10.1016/j.toxlet.2019.06.002

DO - 10.1016/j.toxlet.2019.06.002

M3 - Article

VL - 313

SP - 120

EP - 129

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

ER -