Dig Dis Sci (2006) 51:1426–1433 DOI 10.1007/s10620-006-9088-2 ORIGINAL PAPER Hyperbaric Oxygenation Ameliorates Indomethacin-Induced Enteropathy in Rats by Modulating TNF-α and IL-1β Production Z. Yang · J. Nandi · J. Wang · G. Bosco · M. Gregory · C. Chung · Y. Xie · X. Yang · E. M. Camporesi Received: 8 September 2005 / Accepted: 7 October 2005 / Published online: 13 July 2006 C  Springer Science+Business Media, Inc. 2006 Abstract The effect of hyperbaric oxygenation (HBO 2 ) was investigated in a rat model of indomethacin-induced en- teropathy. Enteropathy was induced by two subcutaneous in- jections of indomethacin (7.5 mg/kg) 24 hr apart. Six groups of rats (n = 8) were treated with and without HBO 2 (100% oxygen at 2.3 atm absolute) for 1 hr once or twice a day for 2 or 5 days. Disease activity index (DAI) and total ulcer length were measured. Other rats were randomized into two groups (n = 16) with and without HBO 2 (1 hr once a day) and four rats were killed in each group at 12, 24, 48, and 72 hr after the final injection of indomethacin. Serum and intestinal mucosal TNF-α, IL-1β , myeloperoxidase (MPO), and iNOS expression was measured. HBO 2 treatment signif- icantly attenuated indomethacin -induced intestinal ulcera- tion and improved DAI. Indomethacin increased MPO activ- ity and iNOS expression, and these were reduced by HBO 2 Z. Yang · J. Wang · G. Bosco · M. Gregory · Y. Xie · X. Yang · E. M. Camporesi Research Laboratory, Department of Anesthesiology, SUNY Upstate Medical University, Syracuse, New York, USA J. Nandi Research Laboratory, Department of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA C. Chung Department of Management Information and Decision Sciences, Syracuse University, Syracuse, New York, 13210, USA Z. Yang () Department of Anesthesiology, Upstate Medical University, 750 East Adams Street, Syracuse, New York, 13210, USA e-mail: yangz@upstate.edu treatment, with a concomitant reduction in TNF-α and IL- 1β . Our data suggest that HBO 2 treatment has a beneficial effect on indomethacin-induced enteropathy and this effect is possibly mediated by decreased production of TNF-α and IL-1β . Keywords Intestinal ulceration . Hyperbaric oxygenation . Myeloperoxidase . TNF-α . IL-1β . Inducible nitric oxide synthase Introduction The etiology and pathogenesis of inflammatory bowel dis- ease (IBD) are still not completely understood. Experimental studies and clinical data suggest that the host immune sys- tem plays an essential role in chronic inflammation. Mul- tiple immune mediators are thought to be involved, in- cluding tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β ). Because of their immunological upregulatory and pro-inflammatory activities, TNF-α and IL-1β play an es- sential role in the pathogenesis of altered intestinal mucosal immune function [1, 2]. TNF-α and IL-1β were found in sub- stantial amounts in the mucosa and stools of patients with IBD [3, 4]. A higher blood level of TNF-α was also found in patients with Crohn’s disease [5], and it was increased in proportion to the severity of indomethacin (INDO)-induced intestinal ulcerations [6]. INDO is a potent nonsteroidal in- flammatory drug that causes acute and chronic intestinal injury in animals as well as humans [7]. Although the mech- anisms of INDO-induced intestinal ulceration and IBD may differ, the fundamental inflammatory processes are similar. INDO-induced intestinal ulceration may provide a useful tool to better understand the pathogenesis of IBD and to search for effective therapies. Springer