title: Ochratoxin A-induced DNA damage in human fibroblast: protective effect of cyanidin 3-O-beta-d-glucoside.
abstract: Ochratoxin A (OTA), a mycotoxin produced by Aspergillus ochraceus and other moulds, has recently received growing attention because of its carcinogenic, teratogenic and nephrotoxic properties in both humans and farm animals. Nevertheless, with regard to the mechanism of toxicity, the data in the literature are inconclusive. The aim of our work was to verify in human fibroblasts treated with different OTA dosages the involvement of oxidative pathway in the damage mechanism of this mycotoxin and the possible protective effect exerted by cyanidin 3-O-beta-D-glucoside (C3G), an anthocyanin present in pigmented oranges, red wines, fruits and vegetables. The addition of OTA at 25 and 50 microM concentrations for 48 h determined only a slight but significant (P<.05) increase in radical oxygen species, whereas a substantial increase in their production was observed at longer exposure, in particular, when the fibroblasts were treated with 50 microM OTA for 72 h. Under the same experimental conditions, our data showed a significant (P<.05) increase in the rupture of cellular membrane and high damage to genomic DNA, evaluated by single-cell gel electrophoresis (comet assay), thus confirming the involvement of oxidative stress in the OTA genotoxicity in agreement with other studies. Diversely, mitochondrial functionality does not appear influenced by OTA treatment. C3G (0.125, 0.250 mM) added to the cells treated with 50 microM OTA significantly reduced free radical species production and prevented genomic DNA damage.
authors.affiliation: Department of Biochemistry, Medical Chemistry and Molecular Biology, University of Catania, Catania 95100, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Russo
authors.forename: Luca
authors.initials: L
authors.lastname: La Fauci
authors.forename: Rosaria
authors.initials: R
authors.lastname: Acquaviva
authors.forename: Agata
authors.initials: A
authors.lastname: Campisi
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Raciti
authors.forename: Christian
authors.initials: C
authors.lastname: Scifo
authors.forename: Marcella
authors.initials: M
authors.lastname: Renis
authors.forename: Giacomo
authors.initials: G
authors.lastname: Galvano
authors.forename: Angelo
authors.initials: A
authors.lastname: Vanella
authors.forename: Fabio
authors.initials: F
authors.lastname: Galvano
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D009793:Ochratoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000032:analysis; D013997:Time Factors
chemical_list: D000872:Anthocyanins; D005960:Glucosides; D009793:Ochratoxins; D017382:Reactive Oxygen Species; C462279:cyanidin-3-O-beta-glucopyranoside; C025589:ochratoxin A