Fosfomycin protects intestinal cells from nuclear changes suggestive of deoxynivalenol-induced apoptosis

PÉREZ GAUDIO, DENISA SOLEDAD; FERNÁNDEZ PAGGI, MARÍA BELÉN; DIEGUEZ, SUSANA NELLY; MOZO, JOAQUÍN; DECUNDO, JULIETA MARÍA; SORACI, ALEJANDRO LUIS; MARTÍNEZ, GUADALUPE; ROMANELLI, AGUSTINA

Journal of Reports in Pharmaceutical Sciences

Wolters Kluwer

Lugar: Philadelphia; Año: 2020 vol. 9 p. 209 - 214

2322-1232

Fosfomycin (FOS) is a broad-spectrum antibiotic which inhibits cell wall synthesis. It has bactericidal activity against both Gram positive and Gram negative bacteria. FOS also promotes phagocytosis, has immunomodulatory effects and protects against the toxicity caused by other drugs. On the other hand, deoxynivalenol (DON) causes cytotoxicity on tissues of rapid growth and fast turnover. The aim of this work was to determine the percentage of nuclear changes indicative of DON-induced apoptosis on intestinal cell cultures (CACO-2) and to evaluate the protective effect of FOS on mycotoxin-exposed cells. Cell cultures were treated as follow: a) DON: 2.8 μg/mL, b) calcium FOS: 580 μg/mL, c) DON 2.8 μg/mL + calcium FOS 580 μg/mL and d) Negative control. Nuclear morphology was evaluated in fixed cells stained with DAPI and then visualized under immunofluorescence microscope. Percentages of cells with nuclear changes were significantly higher in cells treated with DON (31.53 ± 4.17%) compared to those incubated with the antibiotic in conjunction with the mycotoxin (5.63 ± 4.23%). On the contrary, there were no significant differences between cells incubated with DON + FOS and cells incubated only with the antibiotic (1.10 ± 1.55%) when compared to the negative control (3.50 ± 0.09%). The results from this study demonstrated that DON induces nuclear changes suggestive of apoptosis in intestinal cells and that FOS can protect cells from DNA damage. Further studies are needed to determine whether DON induces apoptosis only on cells of epithelial origin and to understand the implications of FOS protective effect under in vivo conditions.