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Int. J. Mol. Sci. 2017, 18(6), 1121; doi:10.3390/ijms18061121

Stability Profiles and Therapeutic Effect of Cu/Zn Superoxide Dismutase Chemically Coupled to O-Quaternary Chitosan Derivatives against Dextran Sodium Sulfate-Induced Colitis

1
Key Laboratory of Chemical Biology (Ministry of Education), Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
2
National Glycoengineering Research Center, Shandong University, Jinan 250012, China
*
Author to whom correspondence should be addressed.
Academic Editor: Manickam Sugumaran
Received: 21 April 2017 / Revised: 6 May 2017 / Accepted: 19 May 2017 / Published: 24 May 2017
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Abstract

Superoxide dismutase (SOD) has attracted considerable attention on treatment of reactive oxygen species (ROS)-related disorders. We previously conjugated Cu/Zn SOD to O-quaternary chitosan derivatives (O-HTCC) to yield a polymer–enzyme conjugate O-HTCC-SOD that demonstrated superior therapeutic effect to native SOD. The present study demonstrated that O-HTCC-SOD had wider pH activity range, better thermal stability, excellent long-term stability for storage, as well as unique reinstatement of activity exposure to proteolytic degradation that was helpful for longer half-life in vivo. O-HTCC-SOD exerted significant anti-inflammatory effects on lipopolysaccharides (LPS)-stimulated mouse peritoneal macrophages by down-regulating production of pro-inflammatory cytokines and intracellular ROS. O-HTCC-SOD significantly attenuated dextran sodium (DSS)-induced colitis in mice as observed by the colitis severity, neutrophil infiltration and histopathological damage, whereas native SOD failed to do so. In conclusion, conjugation of O-HTCC conferred SOD with better stability and enhanced therapeutic potential, offering a promising option in treatment of inflammatory bowel disease. View Full-Text
Keywords: superoxide dismutase; O-quaternary chitosan derivatives (O-HTCC); conjugate; stability; dextran sodium (DSS)-induced colitis; macrophage superoxide dismutase; O-quaternary chitosan derivatives (O-HTCC); conjugate; stability; dextran sodium (DSS)-induced colitis; macrophage
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MDPI and ACS Style

Zhao, N.; Feng, Z.; Shao, M.; Cao, J.; Wang, F.; Liu, C. Stability Profiles and Therapeutic Effect of Cu/Zn Superoxide Dismutase Chemically Coupled to O-Quaternary Chitosan Derivatives against Dextran Sodium Sulfate-Induced Colitis. Int. J. Mol. Sci. 2017, 18, 1121.

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