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

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 alpha) and Interleukin-1beta (IL-1 beta) 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 alpha and IL-1 beta (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 (C) 2010 Elsevier BV All rights reserved