Effects of chitosan oligosaccharide (COS) on the glycerol-induced acute renal failure in vitro and in vivo.

The purpose of this study was to investigate the effects of chitosanoligosaccharide (COS) on the change of inflammatory response, renal function factor, and renal oxidative stress in glycerol-induced ARF in vitro and in vivo. The molecular weight of COS was approximately below 10 kDa with 90% degree of deacetylation. Renal proximal tubular cells were treated with only COS (0, 0.01, 0.025, 0.05, 0.075 and 0.1%) or COS in the presence of glycerol (4mM). And rats were administered with glycerol (50%, 8 ml/kg) by intramuscular injection for the induction of ARF. For identification the protection effect of COS in the glycerol-induced ARF, rats were administered by COS (0.05 and 0.1%) using P.O. injection. The enzymatic activity of the released RDPase was assayed by the fluorometric method. The level of TNF-alpha in kidney or the culture medium was quantified using ELISA kit (R&D Systems, Minneapolis, USA) and, nitrite concentration was determined by the Griess reaction. We showed that COS stimulated the production of TNF-alpha, NO and the released RDPase. Glycerol increased the concentration of RDPase in kidney and decreased the released RDPase in proximal tubular cells. And, glycerol increased the production of NO, TNF-alpha, creatinine, and MDA, and decreased SOD. However, COS recovered the glycerol-induced inflammatory response, renal function factor, and antioxidant effect in kidney. COS had the antioxidant activity and the anti-inflammatory effect. And maybe that characteristics could help recover the glycerol-induced ARF.

Chitosan oligosaccharide (COS) inhibits LPS-induced inflammatory effects in RAW 264.7 macrophage cells.

The focus of this study was to clarify the relation between the nitric oxide (NO) production and cytokine expression including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and also investigated the effect of COS on LPS stimuli from RAW 264.7 cell. The lipopolysaccharide (LPS) of Gram-negative bacteria induces the expression of cytokines and potent inducers of inflammatory cytokines such as TNF-alpha and IL-6. In this experiment, upon stimulation with increasing concentrations of chitosan, the LPS-stimulated TNF-alpha and IL-6 secretion was significantly recovered within the incubation media of RAW 264.7 cells. Consistently, RT-PCR with mRNA and Western blot with anti-cytokine antiserum including TNF-alpha and IL-6 showed that the amount of TNF-alpha and IL-6 secretion in the incubation media recovered with the concentration of chitosan. The LPS-stimulated NO secretion was significantly recovered within the 6h and 12h incubation media of RAW 264.7 cells, too. The recovery effect of chitosan on IL-6 and NO secretion may be induced via the stimulus of TNF-alpha in RAW 264.7 cell. These results once again suggest that chitosan oligosaccharide may have the anti-inflammatory effect via the stimulus of TNF-alpha in the LPS-stimulated inflammation in RAW 264.7 cells.