Protective effect of fosfomycin on deoxynivalenol- treated cell cultures

Abstract

Fosfomycin is a broad-spectrum antibiotic which inhibits cell wall synthesis as it interferes with peptidoglycan production. It has bactericidal activity against both Gram positive and Gram negative bacteria. Because its low toxicity and potential efficacy, the use of fosfomycin has been proposed for animals and humans. Fosfomycin inhibits bacterial adhesion to epithelial cells, penetrates biofilms of exopolysaccharides, promotes phagocytosis, has immunomodulatory effects, and protects against the toxicity caused by other drugs. On the other hand, deoxynivalenol causes cytotoxicity on tissues of rapid growth and fast turnover. The aim of this study was to determine the toxic dose of deoxynivalenol on HEp-2 cell cultures, to determine whether deoxynivalenol induces apoptosis in different cell cultures and to evaluate whether fosfomycin has a protective effect on the cell lines exposed to deoxynivalenol. Toxicity of deoxynivalenol on HEp-2 cells was observed with doses above 1.4 μg/mL. Cells cultures incubated with 2.8 μg/mL of deoxynivalenol and 550 μg/mL of fosfomycin were similar to untreated cells cultures, with preservation of cell monolayer and without cell damage. Apoptotic cell percentage was significantly higher for HEp-2, MDBK and BT cells treated with deoxynivalenol than for cells incubated with both the mycotoxin and the antibiotic. Differences in the percentage of apoptotic cells were not observed between BHK cell cultures treated with deoxynivalenol and for those incubated with both the mycotoxin and the antibiotic. Further studies are needed to determine whether deoxynivalenol induces apoptosis only on cells of epithelial origin and to understand the implications of fosfomycin protective effect under in vivo conditions.