Uridine Ameliorates Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice

被引:71
|
作者
Jeengar, Manish Kumar [1 ,2 ]
Thummuri, Dinesh [2 ]
Magnusson, Mattias [1 ]
Naidu, V. G. M. [2 ,3 ]
Uppugunduri, Srinivas [4 ,5 ]
机构
[1] Linkoping Univ, Dept Clin & Expt Med, AIR, Linkoping, Sweden
[2] Natl Inst Pharmaceut Educ & Res Inst, Dept Pharmacol & Toxicol, Hyderabad 500037, Andhra Prades, India
[3] Natl Inst Pharmaceut Educ & Res Inst, Dept Pharmacol & Toxicol, Gauhati 781032, Assam, India
[4] Linkoping Univ, Reg Canc Ctr South East Sweden, Linkoping, Sweden
[5] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词
INFLAMMATORY-BOWEL-DISEASE; EPITHELIAL-CELLS; PATHOGENESIS; ADHESION; MODEL;
D O I
10.1038/s41598-017-04041-9
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-1 beta 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-alpha, COX-2, P-NFkB and P-Ikk-alpha beta 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-kappa B signaling. Thus, Uridine may be a promising candidate for future use in the treatment of inflammatory bowel disease.
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页数:10
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