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.