Interaction effects of Fusarium enniatins (A, A1, B and B1) combinations on in vitro cytotoxicity of Caco-2 cells. 2014

A Prosperini, and G Font, and M J Ruiz
Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot, Valencia, Spain. Electronic address: Alessandra.Prosperini@uv.es.

Foodstuff is usually contaminated by more than one mycotoxin, however toxicological data are lacking as regards the effects in combinations compared to their individual effect. This study investigated the in vitro effects of enniatins (ENs) A, A1, B and B1, alone and in combinations, on Caco-2 cells viability by MTT assay after 24h of exposure. Cells were treated with concentrations ranging from 0.9 to 15.0μM, individually and in combination of two, three and four mycotoxins. Dose-response curves were generated for each mycotoxin and the isobologram method was used to determine the interactive effects of tested mixtures. Tested ENs produced significant cytotoxic effects both individually and in combination in a dose-dependent manner. IC50 values obtained for all individually tested mycotoxins ranged from 1.3 to >15μM. In ENs combination tests, synergistic effect in Caco-2 viability are observed for EN B+EN A1, EN B1+EN A1 and EN A+EN A1+EN B (CI=0.33-0.52). All other combinations showed additive effect at medium and high affected fraction with exception of lower fraction affected and the EN B+EN B1 mixture that produced antagonistic effect (CI=1.76-10.36). The use of combination index-isobole method could help to better understand the potential interaction between co-occurring mycotoxins and may contribute to their risk assessment.

UI MeSH Term Description Entries
D009183 Mycotoxins Toxic compounds produced by FUNGI. Fungal Toxins,Mycotoxin,Toxins, Fungal
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005670 Fusarium A mitosporic Hypocreales fungal genus, various species of which are important parasitic pathogens of plants and a variety of vertebrates. Teleomorphs include GIBBERELLA. Fusariums
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D047630 Depsipeptides Compounds consisting of chains of AMINO ACIDS alternating with CARBOXYLIC ACIDS via ester and amide linkages. They are commonly cyclized. Cyclic Depsipeptide,Cyclodepsipeptide,Depsipeptide,Peptolide,Peptolides,Cryptophycins,Cyclodepsipeptides,Depsipeptides, Cyclic,Cyclic Depsipeptides,Depsipeptide, Cyclic
D018938 Caco-2 Cells Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells, such as ENTEROCYTES. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation. Caco 2 Cells,Caco-2 Cell,Cell, Caco-2,Cells, Caco-2
D020128 Inhibitory Concentration 50 The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture. IC50,Concentration 50, Inhibitory

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