Cytotoxic effects induced by patulin, deoxynivalenol and toxin T2 individually and in combination in hepatic cells (HepG2)

Food Chem Toxicol. 2018 Oct:120:12-23. doi: 10.1016/j.fct.2018.06.019. Epub 2018 Jun 15.

Abstract

Patulin (PAT), deoxynivalenol (DON) and toxin T-2 (T-2) are mycotoxins distributed worldwide in food and feed. Cytotoxicity of the three mycotoxins individually or in combination in human hepatocellular carcinoma (HepG2) cells was evaluated by MTT assay over 24, 48 and 72 h of exposure. The concentration ranges used were 0.625-15 μM for DON, 1.25-50 nM for T-2 and 0.45-7.5 μM for PAT. The IC50 values obtained ranged from 9.30 to 2.53 μM, from 33.69 to 44.37 nM and from 2.66 to 1.17 μM for DON, T-2 and PAT, respectively. The most cytotoxic mycotoxin to HepG2 cells was T-2 followed by PAT and DON. The combination ratios used for the mixtures were 1:3 (DON: T-2), 1:5 (DON: PAT), 1:1.7 (T-2: PAT) and 1:3:5 (DON: T-2: PAT). The mixture with the highest cytotoxic effect was T-2+PAT, followed by DON + T-2+PAT, DON + T-2 and DON + PAT respect to the cytotoxic effect of their individuals. In the combinations, at low fa an antagonistic effect was detected, and this effect changes the shape of the combination to additive effect at high fa in the mixtures.

Keywords: Cytotoxicity; HepG2 cells; Interactions; Isobologram; Mycotoxins.

MeSH terms

  • Cell Survival / drug effects*
  • Complex Mixtures / toxicity
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Interactions
  • Hep G2 Cells
  • Humans
  • Inhibitory Concentration 50
  • Liver / drug effects*
  • Mycotoxins / administration & dosage
  • Mycotoxins / toxicity*
  • Patulin / administration & dosage
  • Patulin / toxicity*
  • T-2 Toxin / administration & dosage
  • T-2 Toxin / toxicity*
  • Trichothecenes / administration & dosage
  • Trichothecenes / toxicity*

Substances

  • Complex Mixtures
  • Drug Combinations
  • Mycotoxins
  • Trichothecenes
  • Patulin
  • T-2 Toxin
  • deoxynivalenol