The individual and combined effects of ochratoxin A with citrinin and their metabolites (ochratoxin B, ochratoxin C, and dihydrocitrinone) on 2D/3D cell cultures, and zebrafish embryo models

  • Food Chem Toxicol. 2021 Dec:158:112674. doi: 10.1016/j.fct.2021.112674.
Zsolt Csenki  1 ,  Edina Garai  1 ,  Zelma Faisal  2 ,  Rita Csepregi  3 ,  Kitti Garai  4 ,  Dóra Kánainé Sipos  1 ,  István Szabó  1 ,  Tamás Kőszegi  3 ,  Árpád Czéh  5 ,  Tamás Czömpöly  5 ,  Krisztián Kvell  4 ,  Miklós Poór  6
Affiliations
  • 1. Department of Environmental Toxicology, Institute of Aquaculture and Environmental Safety, Hungarian University of Agriculture and Life Sciences, Páter Károly u. 1, H-2100, Gödöllő, Hungary.
  • 2. Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624, Pécs, Hungary; Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624, Pécs, Hungary.
  • 3. Lab-on-a-Chip Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624, Pécs, Hungary; Department of Laboratory Medicine, Medical School, University of Pécs, Ifjúság út 13, H-7624, Pécs, Hungary.
  • 4. Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624, Pécs, Hungary; Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624, Pécs, Hungary.
  • 5. Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624, Pécs, Hungary; Soft Flow Ltd., Ürögi fasor 2/a, H-7634, Pécs, Hungary.
  • 6. Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624, Pécs, Hungary; Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624, Pécs, Hungary. Electronic address: [email protected].
PMID: 34800554 DOI: 10.1016/j.fct.2021.112674
Abstract

Ochratoxin A and citrinin are nephrotoxic mycotoxins produced by Aspergillus, Penicillium, and/or Monascus species. The combined effects of ochratoxin A and citrinin have been examined in more studies; however, only limited data are available regarding the co-exposure to their metabolites. In this investigation, the individual toxic effects of ochratoxin A, ochratoxin B, ochratoxin C, citrinin, and dihydrocitrinone were tested as well as the combinations of ochratoxin A with the latter mycotoxins were examined on 2D and 3D cell cultures, and on zebrafish embryos. Our results demonstrate that even subtoxic concentrations of certain mycotoxins can increase the toxic impact of ochratoxin A. In addition, typically additive effects or synergism were observed as the combined effects of mycotoxins tested. These observations highlight that different cell lines (e.g. MDBK vs. MDCK), cell cultures (e.g. 2D vs. 3D), and models (e.g. in vitro vs. in vivo) can show different (sometimes opposite) impacts. Mycotoxin combinations considerably increased miR-731 levels in zebrafish embryos, which is an early marker of the toxicity on kidney development. These results underline that the co-exposure to mycotoxins (and/or mycotoxin metabolites) should be seriously considered, since even the barely toxic mycotoxins (or metabolites) in combinations can cause significant toxicity.

Keywords
3D cell culture; Citrinin; Combined effects; Dihydrocitrinone; Ochratoxins; Zebrafish embryo.
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