Sulfated chitooligosaccharide selenium alleviates deoxynivalenol-induced intestinal injury in neonatal chicken through modulation of ULK1/LC3-mediated autophagy.

Deoxynivalenol (DON) disrupts intestinal epithelial integrity through oxidative stress and dysregulated autophagy. This study evaluates the efficacy of sulfated chitooligosaccharide selenium (S-COS-Se) in protecting chicken embryos and intestinal epithelial cells from DON-induced intestinal injury. Five hundred 9-day-old embryonated eggs were allocated into 10 groups: Control, Na₂SeO₃, chitosan sulfate, chitosan-selenium, S-COS-Se, DON, and 4 combination groups. Additionally, intestinal epithelial cells were treated with DON alone or combined with various selenium formulations for 24 h. S-COS-Se co-treatment alleviated DON-induced cytotoxicity and restored cell viability while preserving epithelial morphology. S-COS-Se modulated autophagy through PI3K restoration, ULK1 suppression, and LC3-II/LC3-I ratio normalization with reduced p62 accumulation. Transmission electron microscopy confirmed intact mitochondrial cristae and reduced autophagic vacuoles. S-COS-Se attenuated oxidative stress by decreasing levels of malondialdehyde, hydroxyl free radical, and hydrogen peroxide, while enhancing antioxidant enzyme activities. It also restored immune homeostasis through elevated immunoglobulins and suppressed pro-inflammatory cytokines, exhibiting superior efficacy over other selenium compounds. These findings demonstrate that S-COS-Se confers broad protection against DON toxicity by the integrated modulation of ULK1/LC3-mediated autophagy, antioxidant defense, and immune homeostasis. This novel organoselenium compound has potential as a feed additive in poultry diets to protect against mycotoxin-induced intestinal injury.