Organ-specific responses of age-dependent vulnerability to deoxynivalenol in female mice

The responses underlying heightened sensitivity of young populations to deoxynivalenol (DON) toxicity remain uncharacterized in translational murine models. This study aimed to fill this gap by providing the first systematic, multi-organ (intestine, liver, and kidney) comparison of DON toxicity, contrasting the responses of prepubertal and adult mice. Prepubertal (21-day-old) and adult (65-day-old) Swiss mice (n = 10/group) were fed control or 10 mg/kg DON-contaminated diets for 15 or 28 days, respectively. Growth performance was monitored, and intestine, liver, and kidney were subsequently collected for histopathological, morphometric, and biochemical analyses. DON induced a severe, acute weight gain reduction (∼59.6%) in prepubertal mice, with no effect on adults or systemic biochemical profiles. DON toxicity was highly organ-specific: the prepubertal intestine mounted an adaptive response, coupling oxidative damage with compensatory antioxidant production and enterocyte hypertrophy, but without structural lesions. In contrast, the liver and kidney sustained direct histopathological damage in both age groups. However, their biochemical responses diverged: the liver showed a young-specific inflammatory signal, whereas the kidney remained biochemically silent despite the damage it sustained. This multi-organ comparison in mice shows that DON toxicity is age- and organ-specific, demonstrating that at the exposure dose used, prepubertal mice exhibit more pronounced toxic responses.