Adenosine A2A receptors and uric acid mediate protective effects of inosine against TNBS-induced colitis in rats

Eur J Pharmacol. 2010 Dec 15;649(1-3):376-81. doi: 10.1016/j.ejphar.2010.09.044. Epub 2010 Sep 22.


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.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine A2 Receptor Antagonists / pharmacology
  • Animals
  • Biomarkers / metabolism
  • Colitis / chemically induced*
  • Colitis / metabolism
  • Colitis / pathology
  • Dietary Supplements*
  • Drug Synergism
  • Enzyme Inhibitors / therapeutic use
  • Inflammation Mediators / metabolism
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / prevention & control*
  • Inosine Monophosphate / therapeutic use*
  • Lipid Peroxidation / drug effects
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / 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
  • Uric Acid / metabolism*


  • Adenosine A2 Receptor Antagonists
  • Biomarkers
  • Enzyme Inhibitors
  • Inflammation Mediators
  • Receptor, Adenosine A2A
  • Inosine Monophosphate
  • Uric Acid
  • potassium oxonate
  • Oxonic Acid
  • Trinitrobenzenesulfonic Acid
  • Urate Oxidase