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Am J Physiol Gastrointest Liver Physiol (August 28, 2002). doi:10.1152/ajpgi.00060.2002
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Articles in PresS, published online ahead of print August 28, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00060.2002
Submitted on February 13, 2002
Accepted on August 23, 2002

Inosine reduces inflammation and improves survival in a murine model of colitis

Jon G Mabley1*, Pal Pacher1, Lucas Liaudet2, Francisco G Soriano2, Gyorgy Hasko2, Anita Marton1, Csaba Szabo3, and Andrew L Salzman1

1 Inotek Pharmaceuticals Corporation, Beverly, MA, USA
2 Department of Surgery, New Jersey Medical School, Newark, NJ, USA
3 Inotek Pharmaceuticals Corporation, Beverly, MA, USA; Department of Surgery, New Jersey Medical School, Newark, NJ, USA

* To whom correspondence should be addressed. E-mail: jmabley{at}inotekcorp.com.

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 administration of DSS, oral treatment with inosine was commenced either prior to the onset of colitis or as a post treatment once colitis was established. Evaluation of colon damage and inflammation was determined grossly (body weight, 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.




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J. G Mabley, P. Pacher, K. G K Murthy, W. Williams, G. J Southan, A. L Salzman, and C. Szabo
The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes
J. Endocrinol., September 1, 2008; 198(3): 581 - 589.
[Abstract] [Full Text] [PDF]


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