Selenizing chitooligosaccharide with site-selective modification to alleviate acute liver injury in vivo

Two selenized chitooligosaccharide (O-Se-COS and N,O-Se-COS) with different sites modification were synthesized to alleviate liver injury in vivo. Comparing to traditional COS, both selenized COS exhibited enhanced reducibility as well as antioxidant capacity in vitro. Furthermore, O-Se-COS demonstrated superior efficacy in reducing intracellular reactive oxygen species (ROS) and mitochondrial damage compared to N,O-Se-COS as its enhanced cellular uptake by the positive/negative charge interactions. Two mechanisms were proposed to explained these results: one is to enhance the enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which effectively scavenge free radicals; the other is to down-regulate intracellular cytochrome P450 (CYP2E1) levels, inhibiting carbon tetrachloride (CCl₄)-induced peroxidation damage. In vivo studies further demonstrated the effective alleviation of CCl₄-induced liver injury by selenized COS, with therapeutic efficacy observed in the following order: O-Se-COS > N,O-Se-COS > COS. Finally, hemolysis and histological tests confirmed the biosafety of both selenized COS. Taken together, these finding demonstrated that selenium has the potential to improve the biological activity of COS, and precise selenylation was more conducive to achieving the synergistic effect where 1 + 1>2.