Gastro Intestinal Conditions

Gastro Intestinal Conditions –
such as Inflammatory Bowel Disease and Radiation Proctitis

Click on the publications below to view and close the abstracts

Hyperbaric oxygen therapy reduces the severity of necrotizing enterocolitis in a neonatal rat model
Guven A, Gundogdu G, Uysal B, Cermik H, Kul M, Demirbag S, Ozturk H, Oter S.
J Pediatr Surg. 2009 Mar; 44(3):534-40.

INTRODUCTION: Hyperbaric oxygen (HBO) therapy is known to increase oxygen concentration in tissues leading to induction of an adaptive increase in antioxidants, stimulation of angiogenesis, improvement of white blood cell action, and regulation of inflammatory process. Therefore, we tested the potential beneficial effect of HBO in neonatal rat model of necrotizing enterocolitis (NEC).

MATERIALS AND METHODS: Thirty newborn Sprague-Dawley rats, provided by the Experimental Research Council, Gulhane Military Medical Academy, Ankara,Turkey, were randomly divided into 3 groups as follows: NEC, NEC + HBO, and control. Necrotizing enterocolitis was induced by enteral formula feeding and exposure to hypoxia after cold stress at 4 degrees C and oxygen. The NEC + HBO group received HBO at 2.8 atmosphere absolute (ATA) for 90 minutes daily for 3 days. The pups were killed on the fourth day, and their intestinal tissues were harvested for biochemical and histopathologic analysis. Blood samples were also obtained from the pups.

RESULTS: The mortality rate was highest in the NEC group (3 pups in the NEC group vs 1 pup in the NEC + HBO group). Malondialdehyde and protein carbonyl content were significantly increased, whereas superoxide dismutase and glutathione peroxidase were significantly decreased in the NEC group. All these changes were similar to control levels in the NEC group by HBO treatment. Nitrate plus nitrite (NO(x)) levels and serum tumor necrosis factor alpha were increased in the NEC group and histopathologic injury score and apoptosis index in the NEC group were significantly higher than in the NEC + HBO group.

CONCLUSION: Hyperbaric oxygen significantly reduced the severity of NEC in our study.

Hyperbaric oxygen therapy is as effective as dexamethasone in the treatment of TNBS-E-induced experimental colitis
Atug O, Hamzaoglu H, Tahan V, Alican I, Kurtkaya O, Elbuken E, Ozdogan O, Tozun N.
Dig Dis Sci. 2008 Feb;53(2):481-5.

INTRODUCTION: Hyperbaric oxygen (HBO) has been demonstrated to be useful as an adjunctive therapy for Crohn’s disease. In the present study, HBO was tested as a treatment for trinitrobenzenesulfonic acid-ethanol (TNBS-E)-induced distal colitis, and its effects were compared with dexamethasone therapy.

METHODS: A total of 48 Sprague-Dawley rats were separated into six groups: the control, and those treated with vehicle, TNBS-E, HBO, dexamethasone, or combined HBO + dexamethasone. The HBO treatment group was exposed to 100% HBO at 2 ATM for 75 min twice daily at 6-h intervals in a HBO chamber, both on the day of colitis induction and 3 days thereafter. Treatment with intraperitoneal dexamethasone twice daily was started 1 h before the induction of colitis and was continued for 7 days in the dexamethasone group. The rats were decapitated 8 days after the induction of colitis, and the colonic tissue wet weight, macroscopic and microscopic lesion score, and tissue myeloperoxidase (MPO) activity were determined.

RESULTS: HBO therapy decreased the activity of experimental colitis measured by the tissue wet weight, macroscopic score, microscopic score, and MPO activity. The dexamethasone treatment significantly reduced the colitis activity as determined by the tissue MPO activity and wet weight. There were also decreases in the macroscopic and microscopic activity scores with the dexamethasone therapy; however, these changes were not statistically significant. The combined therapy with HBO and dexamethasone provided no additional benefit over HBO therapy alone.

CONCLUSION: HBO therapy can be a valuable therapeutic option in treatment of patients with inflammatory bowel disease. HBO therapy in the refractory patients deserves further, larger clinical studies.

Hyperbaric oxygen enhances the efficiency of 5-aminosalicylic acid in acetic acid-induced colitis in rats
Gorgulu S, Yagci G, Kaymakcioglu N, Ozkara M, Kurt B, Ozcan A, Kaya O, Sadir S, Tufan T.
Dig Dis Sci. 2006 Mar; 51(3):480-7.

The aim of this study was to assess the efficiency of hyperbaric oxygen alone and in combination with 5-aminosalicylic acid in the acetic acid-induced colitis model, a well-known experimental model of inflammatory bowel disease in rats.

Rats were randomly divided into five groups. In the noncolitis control group, rats were given isotonic saline, while in the other groups rats were treated by intracolonic administration of 4% acetic acid. In group 2, the untreated control group, no additional therapy was applied. In groups 3, 4, and 5 hyperbaric oxygen, 5-aminosalicylic acid. and 5-aminosalicylic acid + hyperbaric oxygen therapies were applied, respectively.

Administration of acetic acid caused an inflammatory response in all animals. Histopathologic score was significantly higher in group 2 than in any other group. 5-Aminosalicylic acid and hyperbaric oxygen significantly decreased the histopathologic score (P < 0.05). Myeloperoxidase activity was also reduced significantly by 5-aminosalicylic acid (P < 0.05) but not by hyperbaric oxygen.

The most prominent ameliorative effect, however, was seen in group 5 and the histopathologic score and myeloperoxidase activity were significantly lower than in groups 3 (P < 0.05) and 4 (P < 0.001). Hydroxyproline level also increased significantly in group 5, but not in groups 3 and 4 (P < 0.001).

These findings indicate that hyperbaric oxygen therapy is effective in reducing the extent of colitis induced by acetic acid, although it is not as potent as 5-aminosalicylic acid.

The combination of hyperbaric oxygen and 5-aminosalicylic acid, however, led to a much more prominent reduction in the severity of colitis. Hyperbaric oxygen may have a promising place in the treatment of inflammatory bowel disease.

Effect of hyperbaric oxygen on experimental acute distal colitis
Gulec B, Yasar M, Yildiz S, Oter S, Akay C, Deveci S, Sen D.
Physiol Res. 2004; 53(5):493-9.

It has been demonstrated that hyperbaric oxygen (HBO) is useful as an adjunctive therapy for Crohn’s disease. However, its effects on ulcerative colitis have not been investigated.

In the present study, HBO was tested for acetic acid-induced colitis, and antioxidant systems were evaluated to clarify its possible mode of action. Thirty-six Sprague-Dawley rats were randomly divided into three groups: sham control (Group I), colitis induced by acetic acid without any therapy (Group II), colitis induced by acetic acid and treated with HBO (Group III).

HBO was given for 5 days, 2 sessions per day at 2.5-fold absolute atmosphere pressure (ATA) for a period of 90 min in rats in which colitis had been induced (Group III). Rats were sacrificed on the 5th day after the procedure. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH Px) activity were measured in the intestinal tissue and erythrocyte lysate. MDA and GSH Px were also determined in the plasma. Whereas MDA levels in erythrocyte, plasma and intestinal tissue were decreased, the levels of GSH Px and SOD were significantly increased in Group III as compared to those of Group II.

The results of our study suggest that hyperbaric oxygen therapy has beneficial effects on the course of experimental distal colitis and that antioxidant systems may be involved in its mode of action.

Hyperbaric oxygen therapy for severe ulcerative colitis
Buchman AL, Fife C, Torres C, Smith L, Aristizibal J.
J Clin Gastroenterol. 2001 Oct; 33(4):337-9.

Hyperbaric oxygen therapy has been used to successfully treat perineal Crohn’s disease. We describe the first successful use of hyperbaric oxygen therapy in the treatment of ulcerative colitis, refractory to conventional therapies. Therapy consisted of 30 courses of 100% oxygen at a pressure of 2.0 atm absolute. Clinical remission was achieved on the basis of the Truelove-Witts and disease activity index scores. Corticosteroids were successfully tapered off once remission was achieved.

Hyperbaric oxygen: a novel modality to ameliorate experimental colitis
Rachmilewitz D, Karmeli F, Okon E, Rubenstein I, Better OS
Gut. 1998 Oct; 43(4):512-8.

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.

AIM: 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.

Modification of in Vivo and in Vitro TNF-a, IL-1, and IL-6 Secretion by Circulating Monocytes During Hyperbaric Oxygen Treatment in Patients with Perianal Crohn's Disease
Weisz G, Lavy A, Adir Y, Melamed Y, Rubin D, Eidelman S, and Pollack S
Journal of Clinical Immunology, Vol. 17, No. 2, 1997

Treatment of perianal inflammatory lesions in Crohn’s disease (CD) is unsatisfactory and novel treatment modalities are pursued. We have recently reported a good clinical effect of hyperbaric oxygen (HBO) treatment in perianal CD.

In the present study, seven patients with perianal CD were subjected to daily sessions of HBO in a multiplace hyperbaric chamber. Each patient received a total of 20 sessions during a time period of 1 month, and IL-1, IL-6, and TNF-alpha measurements were done several times during the initial sessions and after completing therapy. Pretreatment cytokine levels were elevated in patients compared to age-matched 10 normal controls.

During the first 7 days of treatment, IL-1, IL-6, and TNF-alpha levels in supernatants of LPS-stimulated monocytes derived from patients’ peripheral blood were decreased compared to pretreatment levels. Parallel measurements of serum IL-1 levels revealed an initial elevation and thereafter decreased levels, which remained low throughout the first week of HBO treatment.

After completion of therapy, cytokine levels increased to pretreatment values. We conclude that alterations in secretion of IL-1, IL-6, and TNF-alpha may be related to the good clinical effect of HBO treatment in CD patients with perianal disease.

Hyperbaric oxygenation as a part of the treatment of chronic ulcerohemorrhagic colitis
Karkŭmov M, Nikolov N, Georgiev L, Mitreva D, Uzunova A.
Vutr Boles. 1991; 30(2):78-80.

34 patients with chronic ulcerohemorrhagic colitis in exacerbation were treated with hyperbaric oxygenation in addition to the routine therapy. Two chambers model “Dräger” 1000 and 1200 were used.

The total course of treatment included 10-12 seances with 60-75 min. exposition each. All patients improved significantly after the first 5-6 seances. The results of the treatment back up the use of hyperbaric oxygenation in the treatment of chronic ulcerohemorrhagic colitis.

Radiation Proctitis

Significant improvement of rectal bleeding, diarrhea and rectal pain is possible using HBOT. HBOT should be offered to patients who fail conventional treatments for radiation proctitis

Treatment of radiation proctitis with hyperbaric oxygen
Jones K, Evans AW, Bristow RG, Levin W.
Radiother Oncol. 2006 Jan; 78(1):91-4. Epub 2005 Dec 7.

BACKGROUND AND PURPOSE: Radiation proctitis is a potential complication following pelvic radiation therapy. There are no standard treatments and treatment outcomes are unpredictable. We report our experience with the use of hyperbaric oxygen treatment (HBOT) for radiation proctitis cases refractory to standard medical or laser therapy.

PATIENTS AND METHODS: During the period 2000-2004, 10 patients with radiation proctitis were treated with HBOT (three males and seven females; mean age of 65). The median follow-up period was 25 months (range 6-43 months). Patient symptoms were retrospectively scored prior to, and following HBOT, based on the LENT-SOMA scale.

RESULTS: Prior to treatment, three patients had Grade 3 toxicity (i.e. requiring blood transfusions) and seven had Grade 2 toxicity with dominant symptoms of rectal pain and/or diarrhoea. HBOT was well tolerated and 9 of the 10 patients completed a full HBOT treatment program. Rectal bleeding completely stopped in four of nine symptomatic patients and improved in three others. Rectal pain completely remitted in three of five symptomatic patients. Diarrhea remitted completely in one of five patients and improved in three others. Of the 10 patients treated, only two did not respond to HBOT.

CONCLUSIONS: Significant improvement of rectal bleeding, diarrhea and rectal pain is possible using HBOT. HBOT should be offered to patients who fail conventional treatments for radiation proctitis.