title: Modulation of macrophage activity by aflatoxins B1 and B2 and their metabolites aflatoxins M1 and M2.
abstract: Aflatoxins are natural contaminants frequently found both in food and feed. Many of them exert immunomodulatory properties in mammals; therefore, the aim of the current study was to investigate immune-effects of AFB1, AFB2, AFM1 and AFM2, alone and differently combined, in J774A.1 murine macrophages. MTT assay showed that AFB1, alone and combined with AFB2, possess antiproliferative activity only at the highest concentration; such effect was not shown by their hydroxylated metabolites, AFM1 and AFM2, respectively. However, the immunotoxic effects of the aflatoxins evaluated in the current study may be due to the inhibition of production of active oxygen metabolites such as NO. Cytofluorimetric assay in macrophages exposed to aflatoxins (10-100 μM) revealed that their cytoxicity is not related to apoptotic pathways. Nevertheless, a significant increase of the S phase cell population accompanied by a decrease in G0/G1 phase cell population was observed after AFB1 treatment. In conclusion, the results of the current study suggest that aflatoxins could compromise the macrophages functions; in particular, co-exposure to AFB1, AFB2, AFM1 and AFM2 may exert interactions which can significantly affect immunoreactivity.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, School of Pharmacy, University of Salerno, via Ponte Don Melillo, 11/c Fisciano (SA), Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bianco
authors.forename: R
authors.initials: R
authors.lastname: Russo
authors.forename: S
authors.initials: S
authors.lastname: Marzocco
authors.forename: S
authors.initials: S
authors.lastname: Velotto
authors.forename: G
authors.initials: G
authors.lastname: Autore
authors.forename: L
authors.initials: L
authors.lastname: Severino
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity; D016607:Aflatoxin M1 / Q000633:toxicity; D000348:Aflatoxins / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis
chemical_list: D000348:Aflatoxins; D009569:Nitric Oxide; D016607:Aflatoxin M1; C029753:aflatoxin B2; D016604:Aflatoxin B1; C030379:aflatoxin M2