Chitosan oligosaccharides protect mice from LPS challenge by attenuation of inflammation and oxidative stress.
Sepsis and its derivative syndromes are major causes of morbidity and mortality in the intensive care unit. Recently, lots of studies have shown that the progression of sepsis is attributed to redox imbalance and overproduction of proinflammatory cytokines. In previous studies, we have reported the anti-oxidative and anti-inflammatory effects of chitosan oligosaccharides in vitro. In the light of these findings, we applied the model of sepsis to mice by LPS injection to investigate whether chitosan oligosaccharides have a protective effect on LPS-induced sepsis. We found that treatment by chitosan oligosaccharides not only attenuated organ dysfunction but also improved survival rate after LPS injection. To further understand how it works, we examined several proinflammatory markers including neutrophil infiltration in organs and TNF-α and IL-1β in serum, and found that these cytokines were significantly reduced by chitosan oligosaccharide treatment. In addition to this, anti-oxidants including glutathione (GSH) and catalase (CAT) levels were depleted and malondialdehyde (MDA) levels were increased in LPS-induced sepsis, while chitosan oligosaccharides smoothed out the redox imbalance. Furthermore, we also assessed c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase signal activation by LPS-stimulation, and found both of them were attenuated by chitosan oligosaccharide treatment. Collectively, our data demonstrated that chitosan oligosaccharides can protect mice from the LPS challenge by virtue of anti-inflammatory effects as well as anti-oxidation properties, which might offer beneficial effects for patients with sepsis.
Liaoning Provincial Key Laboratory of Carbohydrates, Department of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, Liaoning 116023, China.
Ying
Y
Qiao
Xue-Fang
XF
Bai
Yu-Guang
YG
Du
D000818:Animals; D002374:Catalase / Q000378:metabolism; D048271:Chitosan / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D009844:Oligosaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects*; D018805:Sepsis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016019:Survival Analysis
D016207:Cytokines; D008070:Lipopolysaccharides; D009844:Oligosaccharides; C482199:lipopolysaccharide, E coli O55-B5; D048271:Chitosan; D002374:Catalase; D005978:Glutathione