title: Oxidative DNA damage and disturbance of antioxidant capacity by alternariol in Caco-2 cells.
abstract: Oxidative stress occurs as a consequence of an imbalance between the prooxidant/antioxidant systems, causing an increase of intracellular generation of reactive oxygen species. Alternariol (AOH), a mycotoxin produced by Alternaria sp. can alter the action of glutathione (GSH) and the enzymes involved in the redox system, causing damage to cellular macromolecules such as DNA. The aims of this work were to determine the induction of oxidative stress by the antioxidant defenses imbalance in relation to glutathione (GSH), glutathione reductase (GR), glutathione transferase (GST), glutathione peroxidase (GPx) levels and DNA damage in Caco-2 cells derived from adenocarcinoma human colon. Oxidative stress by AOH was confirmed by alteration of GSH levels and the antioxidant defense system after 15, 30 and 60 μM AOH exposure during 24h. GSH levels significantly decreased by 43% after treatment with 60 μM AOH compared to the control. The activity of GPx and GR was reduced by 30% and 23%, respectively after 60 μM AOH. The GST activity was significantly increased (approximately 22%) with 30 μM AOH, while 60 μM AOH decreased it by 30% in comparison to the control. Analysis of DNA damage was performed using the Comet assay after 24h, where the % of DNA in tail increased from 70% to 85% compared the control.
authors.affiliation: Laboratory of Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain. Electronic address: celia.fernandez-blanco@uv.es.
authors.forename: Celia
authors.initials: C
authors.lastname: Fernández-Blanco
authors.affiliation: Laboratory of Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Guillermina
authors.initials: G
authors.lastname: Font
authors.affiliation: Laboratory of Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Ruiz
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D018938:Caco-2 Cells; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000633:toxicity*; D009183:Mycotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D007783:Lactones; D009183:Mycotoxins; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; C005197:alternariol
keywords: Alternariol; Antioxidant enzymes; Caco-2 cells; Comet assay; Cytotoxicity; Glutathione