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
[1]   URIC-ACID PROVIDES AN ANTIOXIDANT DEFENSE IN HUMANS AGAINST OXIDANT-CAUSED AND RADICAL-CAUSED AGING AND CANCER - A HYPOTHESIS [J].
AMES, BN ;
CATHCART, R ;
SCHWIERS, E ;
HOCHSTEIN, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (11) :6858-6862
[2]   ROLE OF EXTRACELLULAR ATP AND P1 AND P2 CLASSES OF PURINERGIC RECEPTORS IN T-CELL DEVELOPMENT AND CYTOTOXIC T-LYMPHOCYTE EFFECTOR FUNCTIONS [J].
APASOV, S ;
KOSHIBA, M ;
REDEGELD, F ;
SITKOVSKY, MV .
IMMUNOLOGICAL REVIEWS, 1995, 146 :5-19
[3]   PURINE NUCLEOTIDE-METABOLISM IN RESIDENT AND ACTIVATED RAT MACROPHAGES INVITRO [J].
BARANKIEWICZ, J ;
COHEN, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1985, 15 (06) :627-631
[4]   URIC-ACID AS RADICAL SCAVENGER AND ANTIOXIDANT IN THE HEART [J].
BECKER, BF ;
REINHOLZ, N ;
OZCELIK, T ;
LEIPERT, B ;
GERLACH, E .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1989, 415 (02) :127-135
[5]  
Bennett CF, 1997, J PHARMACOL EXP THER, V280, P988
[6]   ACTION OF PURINE NUCLEOSIDES ON THE RELEASE OF INTRACELLULAR ENZYMES FROM RAT LYMPHOCYTES [J].
COLE, AWG ;
PALMER, TN .
CLINICA CHIMICA ACTA, 1979, 92 (01) :93-100
[7]  
COOPER HS, 1993, LAB INVEST, V69, P238
[8]   ADENOSINE, AN ENDOGENOUS ANTIINFLAMMATORY AGENT [J].
CRONSTEIN, BN .
JOURNAL OF APPLIED PHYSIOLOGY, 1994, 76 (01) :5-13
[9]   SUPERFICIAL NEPHRON OBSTRUCTION AND MEDULLARY CONGESTION AFTER ISCHEMIC-INJURY - EFFECT OF PROTECTIVE TREATMENTS [J].
DEROUGEMONT, D ;
BRUNNER, FP ;
TORHORST, J ;
WUNDERLICH, PF ;
THIEL, G .
NEPHRON, 1982, 31 (04) :310-320
[10]  
Dieleman LA, 1998, CLIN EXP IMMUNOL, V114, P385