title: Nivalenol induces oxidative stress and increases deoxynivalenol pro-oxidant effect in intestinal epithelial cells.
abstract: Mycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6, the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kB and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern.
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132-84084 Fisciano, Salerno, Italy.
authors.forename: Marisanta
authors.initials: M
authors.lastname: Del Regno
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132-84084 Fisciano, Salerno, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Adesso
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132-84084 Fisciano, Salerno, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Popolo
authors.affiliation: Department of Biomedical Sciences, Cornell University, Veterinary Research Tower, Cornell University, Ithaca, NY 14853-6401, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Quaroni
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132-84084 Fisciano, Salerno, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Autore
authors.affiliation: Department of Pathology and Animal Health, Division of Toxicology, School of Veterinary Medicine, University of Naples "Federico II", Via Delpino 1, 80137 Naples, Italy.
authors.forename: Lorella
authors.initials: L
authors.lastname: Severino
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132-84084 Fisciano, Salerno, Italy. Electronic address: smarzocco@unisa.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Marzocco
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009183:Mycotoxins / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D009183:Mycotoxins; D016877:Oxidants; D017382:Reactive Oxygen Species; D014255:Trichothecenes; D013481:Superoxides; C002744:3-nitrotyrosine; D014443:Tyrosine; C038405:nivalenol; D051547:Heme Oxygenase-1; C007262:deoxynivalenol
keywords: Deoxynivalenol; Intestinal epithelial cells; Mycotoxins combination; Nivalenol; Oxidative stress