Inosine reduces inflammation and improves survival in a murine model of colitis

被引:84
作者
Mabley, JG
Pacher, P
Liaudet, L
Soriano, FG
Haskó, G
Marton, A
Szabó, C
Salzman, AL
机构
[1] Inotek Pharmaceut, Beverly, MA 01915 USA
[2] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2003年 / 284卷 / 01期
关键词
colon; dextran sodium sulfate; cytokines; purine;
D O I
10.1152/ajpgi.00060.2002
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Inosine, a naturally occurring purine formed from the breakdown of adenosine, has recently been shown to exert powerful anti-inflammatory effects both in vivo and in vitro. This study evaluated inosine as a potential therapy for colitis. Colitis was induced in mice by the administration of dextran sulfate sodium (DSS). Oral treatment with inosine was begun either before the onset of colitis or as a posttreatment once colitis was established. Evaluation of colon damage and inflammation was determined grossly (body wt, rectal bleeding), histologically, and biochemically (colon levels of MPO, MDA, and cytokines). DSS-induced colitis significantly increased inflammatory cell infiltration into the colon. DSS-induced colitis also increased colon levels of lipid peroxidation, cytokines, and chemokines. Inosine protected the colon from DSS-induced inflammatory cell infiltration and lipid peroxidation. Inosine also partially reduced these parameters in an experimental model of established colitis. Thus inosine treatment may be a potential therapy in colitis.
引用
收藏
页码:G138 / G144
页数:7
相关论文
共 44 条
[31]   A NOVEL METHOD IN THE INDUCTION OF RELIABLE EXPERIMENTAL ACUTE AND CHRONIC ULCERATIVE-COLITIS IN MICE [J].
OKAYASU, I ;
HATAKEYAMA, S ;
YAMADA, M ;
OHKUSA, T ;
INAGAKI, Y ;
NAKAYA, R .
GASTROENTEROLOGY, 1990, 98 (03) :694-702
[32]   ANTISERUM TO TUMOR-NECROSIS-FACTOR AND FAILURE TO PREVENT MURINE COLITIS [J].
OLSON, AD ;
DELBUONO, EA ;
BITAR, KN ;
REMICK, DG .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 1995, 21 (04) :410-418
[33]  
Sajjadi FG, 1996, J IMMUNOL, V156, P3435
[34]  
SCHRIER DJ, 1990, J IMMUNOL, V145, P1874
[35]   Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease [J].
Singer, II ;
Kawka, DW ;
Scott, S ;
Weidner, JR ;
Mumford, RA ;
Riehl, TE ;
Stenson, WF .
GASTROENTEROLOGY, 1996, 111 (04) :871-885
[36]   Inosine improves gut permeability and vascular reactivity in endotoxic shock [J].
Soriano, FG ;
Liaudet, L ;
Marton, A ;
Haskó, G ;
Lorigados, CB ;
Deitch, EA ;
Szabó, C .
CRITICAL CARE MEDICINE, 2001, 29 (04) :703-708
[37]   Role of poly(ADP-ribose) synthetase in inflammation and ischaemia-reperfusion [J].
Szabó, C ;
Dawson, VL .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1998, 19 (07) :287-298
[38]   Role of poly-ADP ribosyltransferase activation in the vascular contractile and energetic failure elicited by exogenous and endogenous nitric oxide and peroxynitrite [J].
Szabo, C ;
Zingarelli, B ;
Salzman, AL .
CIRCULATION RESEARCH, 1996, 78 (06) :1051-1063
[39]   Suppression of macrophage in inflammatory protein (MIP)-1α production and collagen-induced arthritis by adenosine receptor agonists [J].
Szabó, C ;
Scott, GS ;
Virág, L ;
Egnaczyk, G ;
Salzman, AL ;
Shanley, TP ;
Haskó, G .
BRITISH JOURNAL OF PHARMACOLOGY, 1998, 125 (02) :379-387
[40]   Intravenous nucleosides and a nucleotide promote healing of small bowel ulcers in experimental enterocolitis [J].
Veerabagu, MP ;
Meguid, MM ;
Oler, A ;
Levine, RA .
DIGESTIVE DISEASES AND SCIENCES, 1996, 41 (07) :1452-1457