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Murine Colitis Modeling using Dextran Sulfate Sodium DSS
Published on: January 19, 2010
Uridine Ameliorates Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice
Manish Kumar Jeengar1,2, Dinesh Thummuri3, Mattias Magnusson4
1Autoimmunity & Immune Regulation (AIR), Department of Clinical & Experimental Medicine, Linköping University, Linköping, Sweden. manish.pharmacology@live.in.
Abstract:
Uridine, one of the four components that comprise RNA, has attracted attention as a novel therapeutic modulator of inflammation. However, very little is known about its effect on intestinal inflammation. The aim of the present study was to investigate the potential protective effect of intracolonic administered uridine against DSS induced colitis in male C57BL/6 mice. Intracolonic instillation of 3 doses of uridine 1 mg/Kg (lower dose), 5 mg/Kg (medium dose), and 10 mg/Kg (higher dose) in saline was performed daily. Uridine at medium and high dose significantly reduced the severity of colitis (DAI score) and alleviated the macroscopic and microscopic signs of the disease. The levels of proinflammatory cytokines IL-6, IL-1β and TNF in serum as well as mRNA expression in colon were significantly reduced in the uridine treated groups. Moreover, colon tissue myloperoxidase activities, protein expression of IL-6, TNF- α, COX-2, P-NFkB and P-Ikk-βα in the colon tissues were significantly reduced in medium and high dose groups. These findings demonstrated that local administration of uridine alleviated experimental colitis in male C57BL/6 mice accompanied by the inhibition of neutrophil infiltration and NF-κB signaling. Thus, Uridine may be a promising candidate for future use in the treatment of inflammatory bowel disease.
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