title: Cytotoxic effects and degradation products of three mycotoxins: alternariol, 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol in liver hepatocellular carcinoma cells.
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%.
authors.affiliation: Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, València, Spain. Electronic address: ana.juan@uv.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Juan-García
authors.affiliation: Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, València, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Juan
authors.affiliation: Department of Nutrition and Home Economics, Faculty of Life Science, University of Applied Science Hamburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: König
authors.affiliation: Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, València, Spain.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Ruiz
mesh_terms: D001711:Biotransformation; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D056148:Chromatography, Reverse-Phase; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000378:metabolism* / Q000633:toxicity; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D013464:Sulfuric Acids / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014255:Trichothecenes / Q000378:metabolism* / Q000633:toxicity
chemical_list: D007783:Lactones; D013464:Sulfuric Acids; D014255:Trichothecenes; C043247:3-acetyldeoxynivalenol; C046760:15-acetyldeoxynivalenol; D005978:Glutathione; D003545:Cysteine; C005197:alternariol
keywords: Cytotoxicity; HepG2 cells; Metabolites; Mycotoxins