Document Detail


Adenosine A2A receptors and uric acid mediate protective effects of inosine against TNBS-induced colitis in rats.
MedLine Citation:
PMID:  20868668     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inflammatory bowel disease comprises chronic recurrent inflammation of gastrointestinal tract. This study was conducted to investigate inosine, a potent immunomodulator, in 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced chronic model of experimental colitis, and contribution of adenosine A(2A) receptors and the metabolite uric acid as possible underlying mechanisms. Experimental colitis was rendered in rats by a single colonic administration of 10 mg of TNBS. Inosine, potassium oxonate (a hepatic uricase inhibitor), SCH-442416 (a selective adenosine A(2A) receptor antagonist), inosine+potassium oxonate, or inosine+SCH-442416 were given twice daily for 7 successive days. At the end of experiment, macroscopic and histopathologic scores, colonic malondialdehyde (MDA), Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-1beta (IL-1β) levels, and myeloperoxidase (MPO) activity were assessed. Plasma uric acid level was measured throughout the experiment. Both macroscopic and histological features of colonic injury were markedly ameliorated by either inosine, oxonate or inosine+oxonate. Likewise, the elevated amounts of MPO and MDA abated as well as those of TNF-α and IL-1β (P<0.05). SCH-442416 partially reversed the effect of inosine on theses markers, while inosine+oxonate showed a higher degree of protection than each treatment alone (P<.0.05). No significant difference was observed between TNBS and SCH-442416 groups. Uric acid levels were significantly higher in inosine or oxonate groups compared to control. Inosine+oxonate resulted in an even more elvelated uric acid level than each treatment alone (P<0.05). Inosine elicits notable anti-inflammatory effects on TNBS-induced colitis in rats. Uric acid and adenosine A(2A) receptors contribute to these salutary properties.
Authors:
Reza Rahimian; Gohar Fakhfouri; Ali Daneshmand; Hamed Mohammadi; Arash Bahremand; Mohammad Reza Rasouli; Kazem Mousavizadeh; Ahmad Reza Dehpour
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2010-09-22
Journal Detail:
Title:  European journal of pharmacology     Volume:  649     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2011-03-03     Revised Date:  2011-05-23    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  376-81     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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MeSH Terms
Descriptor/Qualifier:
Adenosine A2 Receptor Antagonists / pharmacology
Animals
Biological Markers / metabolism
Colitis / chemically induced*,  metabolism,  pathology
Dietary Supplements*
Drug Synergism
Enzyme Inhibitors / therapeutic use
Inflammation Mediators / metabolism
Inflammatory Bowel Diseases / immunology,  pathology,  prevention & control*
Inosine Monophosphate / therapeutic use*
Lipid Peroxidation / drug effects
Macrophages / drug effects,  metabolism,  pathology
Male
Neutrophil Infiltration / drug effects
Oxonic Acid / therapeutic use
Random Allocation
Rats
Rats, Sprague-Dawley
Receptor, Adenosine A2A / metabolism*
Severity of Illness Index
Trinitrobenzenesulfonic Acid / toxicity*
Urate Oxidase / antagonists & inhibitors
Uric Acid / blood,  metabolism*
Chemical
Reg. No./Substance:
0/Adenosine A2 Receptor Antagonists; 0/Biological Markers; 0/Enzyme Inhibitors; 0/Inflammation Mediators; 0/Receptor, Adenosine A2A; 0/potassium oxonate; 131-99-7/Inosine Monophosphate; 2508-19-2/Trinitrobenzenesulfonic Acid; 69-93-2/Uric Acid; 937-13-3/Oxonic Acid; EC 1.7.3.3/Urate Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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