Fosfomycin Protects Intestinal Cells from Nuclear Changes Suggestive of Deoxynivalenol-induced Apoptosis

PERÉZ GAUDIO DENISA; MOZO JOAQUIN; MARTINEZ GUADALUPE; FERNÁNDEZ PAGGI BELEN; DECUNDO JULIETA MARÍA; ROMANELLI AGUSTINA; DIEGUEZ SUSANA NELLY; ALEJANDRO L. SORACI,

Journal of Reports in Pharmaceutical Sciences

Medknow

Año: 2020 vol. 9 p. 209 - 214

2322-1232

Fosfomycin (FOS) is a broad-spectrum antibiotic which inhibits cell wall synthesis. It25 has bactericidal activity against both Gram positive and Gram negative bacteria. FOS also26 promotes phagocytosis, has immunomodulatory effects and protects against the toxicity caused27 by other drugs. On the other hand, deoxynivalenol (DON) causes cytotoxicity on tissues of28 rapid growth and fast turnover. The aim of this work was to determine the percentage of nuclear29 changes indicative of DON-induced apoptosis on intestinal cell cultures (CACO-2) and to30 evaluate the protective effect of FOS on mycotoxin-exposed cells. Cell cultures were treated as31 follow: a) DON: 2.8 µg/mL, b) calcium FOS: 580 µg/mL, c) DON 2.8 µg/mL + calcium FOS32 580 µg/mL and d) Negative control. Nuclear morphology was evaluated in fixed cells stained33 with DAPI and then visualized under immunofluorescence microscope. Percentages of cells34 with nuclear changes were significantly higher in cells treated with DON (31.53 ± 4.17%)35 compared to those incubated with the antibiotic in conjunction with the mycotoxin (5.63 ±36 4.23%). On the contrary, there were no significant differences between cells incubated with37 DON + FOS and cells incubated only with the antibiotic (1.10 ± 1.55%) when compared to the38 negative control (3.50 ± 0.09%). The results from this study demonstrated that DON induces39 nuclear changes suggestive of apoptosis in intestinal cells and that FOS can protect cells from40 DNA damage. Further studies are needed to determine whether DON induces apoptosis only41 on cells of epithelial origin and to understand the implications of FOS protective effect under42 in vivo conditions