Deoxynivalenol-induced apoptosis and IL-1β modulation by fosfomycin in porcine immune and human intestinal epithelial cells

Abstract

Deoxynivalenol is a trichothecene mycotoxin found in cereals and animal feed, causing immunotoxic and cytotoxic effects in both animals and humans. In pigs, deoxynivalenol induces immune cell apoptosis, while in humans it disrupts cytokine expression and gut barrier function. Fosfomycin is a broad-spectrum antibiotic with immunomodulatory and antimicrobial properties. The aim of this study was to evaluate the effects of fosfomycin on deoxynivalenol-induced apoptosis and on the expression of the proinflammatory cytokine interleukin-1 beta (IL-1β), in pig and human cells, respectively. Porcine adherent mononuclear cells were exposed to deoxynivalenol, fosfomycin, or their combination for 4 h while Caco-2 cells were treated for 24 h. Nuclear apoptotic changes in porcine cells were assessed by DAPI staining and cell death was confirmed by TUNEL assay. IL-1β gene expression in Caco-2 cells was evaluated by RT-qPCR. Deoxynivalenol significantly increased nuclear morphological alterations and the percentage of apoptotic cells in porcine mononuclear cells compared with untreated controls (p < 0.01). Co-treatment with fosfomycin prevented DON-induced apoptosis, restoring apoptotic levels to those observed in controls, and markedly reduced IL-1β expression in Caco-2 cells. Fosfomycin exerts a protective effect against deoxynivalenol-induced apoptosis and proinflammatory response, suggesting its potential as modulator of mycotoxin-induced cellular damage in both veterinary and biomedical contexts.