title: Alternariol induce toxicity via cell death and mitochondrial damage on Caco-2 cells.
abstract: Alternariol (AOH), a mycotoxin produced by Alternaria sp, appears as food contaminant in fruit, vegetables and cereal products. Its toxicity has been demonstrated, but the mechanisms involved have not been elucidated yet. In this study, the pathways triggered by AOH and degradation products generated on Caco-2 cells were evaluated. Cells were exposed to AOH sub-cytotoxic concentrations of 15, 30 and 60 μM. Cell cycle disruption, the induction of apoptosis/necrosis and changes in mitochondrial membrane potential (Δψm) after 24 and 48 h was asses by flow cytometry. Also, AOH and its degradation products were evaluated after 24 and 48 h by high-performance liquid chromatography with tandem mass spectrometric (LC-MS/MS) to detect and quantify its levels. Cell cycle was significantly decreased at G1 phase and increased at S and G2/M phase at the time of exposure. AOH induced necrosis, apoptosis/necrosis and loss of Δψm in a dose and time-dependent manner. The concentrations of AOH quantified in the culture media exposed to AOH decreased as the exposure time was increased. In conclusion, AOH caused cytotoxic effects supported by blocking cell cycle, decreasing cell proliferation and increasing apoptosis/necrosis cells.
authors.affiliation: Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot, Valencia, 46100, Spain. Electronic address: celia.fernandez-blanco@uv.es.
authors.forename: Celia
authors.initials: C
authors.lastname: Fernández-Blanco
authors.affiliation: Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot, Valencia, 46100, Spain.
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, Burjassot, Valencia, 46100, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Juan
authors.affiliation: Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot, Valencia, 46100, Spain.
authors.forename: Guillermina
authors.initials: G
authors.lastname: Font
authors.affiliation: Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, Burjassot, Valencia, 46100, Spain.
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Ruiz
mesh_terms: D000528:Alternaria / Q000378:metabolism; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*
chemical_list: D007783:Lactones; C005197:alternariol
keywords: Alternariol; Caco-2 cells; Cell cycle; Degradation products; LC–MS/MS; Membrane potential; Necrosis-apoptosis