Hyperbaric oxygen: a novel modality to ameliorate experimental colitis.
BACKGROUND
Hyperbaric oxygen (HBO) has been suggested to be beneficial in inflammatory bowel disease but the mechanisms responsible for its therapeutic effects have not been elucidated.


OBJECTIVE
To assess the effect of HBO treatment on colonic damage in two models of experimental colitis, and to examine whether this effect is mediated by modulation of NO synthesis.


METHODS
Colitis was induced by either flushing the colon with 2 ml 5% acetic acid or intracolonic administration of 30 mg trinitrobenzenesulphonic acid (TNB) dissolved in 0.25 ml 50% ethanol. Rats were exposed to HBO (100% oxygen at 2.4 atmosphere absolute) for one hour twice on the day of colitis induction and once daily thereafter. Control rats were treated only with acetic acid or TNB. Rats were killed 24 hours after acetic acid administration or one and seven days after TNB treatment. The colon was isolated, washed, and weighed, the lesion area was measured, and mucosal scrapings were processed for determination of myeloperoxidase (MPO) and NO synthase (NOS) activities, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) generation.


RESULTS
In control rats exposed for seven days to HBO, colonic NOS activity was significantly decreased by 61%, compared with its activity in untreated rats (2.93 (0.17) nmol/g/min). HBO significantly reduced by 51 and 62% the extent of injury induced by acetic acid and TNB respectively. The protection provided by HBO was accompanied by a significant decrease in colonic weight, PGE2 generation, MPO, and NOS activities. In acetic acid colitis, LTB4 generation was also significantly decreased.


CONCLUSIONS
(1) HBO effectively decreases colitis induced by acetic acid and TNB. (2) The decreased NOS activity induced by HBO suggests that reduction in NO generation may be among the mechanisms responsible for the anti-inflammatory effect of HBO. (3) HBO may be considered in the treatment of patients with refractory inflammatory bowel disease.
Rachmilewitz
D
D
Departments of Medicine and Pathology, Hadassah University Hospital, Mount Scopus, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Karmeli
F
F
Okon
E
E
Rubenstein
I
I
Better
O S
OS
D019342:Acetic Acid / Q000009:adverse effects; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology / Q000628:therapy*; D006931:Hyperbaric Oxygenation; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009195:Peroxidase; D019001:Nitric Oxide Synthase; D019342:Acetic Acid