Chitosan-Zn Chelate Downregulates TLR4-NF-κB Signal Pathway of Inflammatory Response and Cell Death-Associated Proteins Compared to Inorganic Zinc.

The study was conducted to investigate the effect of chitosan-zinc chelate (CS-Zn) on TLR4-NF-κB signaling pathway and cell death-associated proteins in a weanling pig model. A total of 90 weaned piglets were allotted to three dietary treatments (the dietary treatments were as follows: (1) experimental diet with supplemental ZnSO (150 mg Zn/kg diet), (2) experimental diet with supplemental CS-Zn (150 mg Zn/kg diet), and (3) experimental diet with a supplemental mixture of chitosan and ZnSO (150 mg/kg Zn; the content of chitosan was equal to CS-Zn, which is according to molar basis)). The feeding trial lasted 30 days. The results showed that compared with ZnSO or CS+ZnSO, CS-Zn decreased the expressions of the cell death-associated proteins Beclin-1, and Cleaved-Caspase3 and the ratio of LC3II/LC3I. The intestinal expressions of TLR4 and its downstream signals NF-κB, IKKβ, and IκBα were down-regulated simultaneously. Moreover, the contents of pro-inflammatory cytokines IL-2, TNF-α, and IFN-γ were decreased. The results indicated that as organic zinc source, CS-Zn was more effective than ZnSO and the mixture of chitosan and ZnSO for inhibiting inflammatory response and decreasing the expressions of proteins associated with cell death. The great anti-inflammatory effect of CS-Zn was modulated by inhibiting the TLR4-NF-κB signaling pathway, and the effect of CS-Zn on down-regulating the expression of cell death-associated proteins might also closely be associated with the TLR4-NF-κB signaling pathway.