Cytotoxic effects and degradation products of three mycotoxins: alternariol, 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol in liver hepatocellular carcinoma cells

Toxicol Lett. 2015 May 19;235(1):8-16. doi: 10.1016/j.toxlet.2015.03.003. Epub 2015 Mar 12.

Abstract

This work is focused in studying the cytotoxic effects on HepG2 cells of the mycotoxins alternariol (AOH), 3-acetyl-deoxynivalenol (3-ADON) and 15-acetyl-deoxynivalenol (15-ADON) by the MTT assay, as well as in the identification of the degradation products and/or metabolites originated after treatment by liquid chromatography tandem mass spectrometry (LC-MS/MS) equipment and extracted from culture media. HepG2 cells were treated at different concentrations over 24, 48 and 72 h. The IC50 values were from 65 to 96 μM, from 3.6 to 6.2 μM and from 5.2 to 8.1 μM for AOH, 3-ADON and 15-ADON, respectively. Among all three mycotoxins assayed, deoxynivalenol (DON) derivated presented the highest toxic potential. Mass spectrometry (MS) scan chromatograms of studied mycotoxins allowed to detect products from: (i) the glutathione conjugate: (ii) sulfuric acid conjugated and (iii) amino group of cysteine conjugate. At all assayed times, the increase of recoveries values was obtained in a concentration dependent manner to finally decrease in the following ranking: 72 h>24h>48 h. The abundance relative (%) obtained for AOH's gluthathione ion product oscillated between 48 and 80% while for 3-ADON's ranged from 50 to 80%.

Keywords: Cytotoxicity; HepG2 cells; Metabolites; Mycotoxins.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotransformation
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Survival / drug effects
  • Chromatography, Reverse-Phase
  • Cysteine / analogs & derivatives
  • Cysteine / metabolism
  • Dose-Response Relationship, Drug
  • Glutathione / analogs & derivatives
  • Glutathione / metabolism
  • Hep G2 Cells
  • Humans
  • Inhibitory Concentration 50
  • Lactones / metabolism*
  • Lactones / toxicity
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Sulfuric Acids / metabolism
  • Tandem Mass Spectrometry
  • Time Factors
  • Trichothecenes / metabolism*
  • Trichothecenes / toxicity

Substances

  • Lactones
  • Sulfuric Acids
  • Trichothecenes
  • 3-acetyldeoxynivalenol
  • 15-acetyldeoxynivalenol
  • Glutathione
  • Cysteine
  • alternariol