aDepartment of Immunology, The Forsyth Institute, Boston, MA, USA
bSkyview Enterprises, New York, NY, USA
Received 18 May 2009.
Available online 30 May 2009.
Abstract
By its antioxidant effect, molecular hydrogen gas (H2) was reported to protect organs from tissue damage induced by ischemia reperfusion. To evaluate its anti-inflammatory effects, we established a mouse model of human inflammatory bowel disease (IBD) by supplying mice with water containing (1) dextran sodium sulfate (DSS) (5%), (2) DSS (5%) and H2, or (3) H2 only ad libitum up to 7 days. At day-7, DSS-induced pathogenic outcomes including, loss of body weight, increase of colitis score, pathogenic shortening of colon length, elevated level of IL-12, TNF-α and IL-1β in colon lesion, were significantly suppressed by the addition of H2 to DSS solution. Histological analysis also revealed that the DSS-mediated colonic tissue destruction accompanied by macrophage infiltration was remarkably suppressed by H2. Therefore, the present study indicated that H2 can prevent the development of DSS-induced colitis in mice.
Fig. 1. Effects of H2 on the clinical features of DSS-induced colitis in BALB/c mice. Temporal change of H2 concentration in stomach (A) and in colon (B) after the oral administration of H2-saturated water to mice (n = 5/each time point) was monitored. Distilled water saturated with H2 (0.78 mM, ORP = −511 mV, pH 7.67) was applied to mice using a Popper® feeding needle (1 ml/mouse). Immediately after the sacrifice of animals in each group, H2 concentrations of liquid substance present in stomach and colon were measured. To examine the effects of H2 on DSS-induced colitis, H2 (0.78 mM) water alone or 5% DSS with or without H2-water were administered to mice (8 w males, n = 6/group) ad libitum for 7 days. The percent of body weight change (C) and colitis score (D) were measured on a daily basis. Data points and bars of H2-water alone (♦), 5% DSS water alone (□), and 5% DSS including H2-water () indicate means ± SD. *p < 0.05, **p < 0.01: Value is significantly different from the control group receiving DSS alone in the same measurement day (t-test).
Fig. 2. H2-mediated alleviation of colon contraction induced by DSS. To assess the severity of colitis, regular water, H2 (0.78 mM) water alone, or 5% DSS with or without H2-water were administered to mice for 7 days after which the colon length was measured. (A) Representative macroscopic features of the colons isolated from mice treated with regular water (Control), H2-containing water (H2), 5% DSS water (DSS) and 5% DSS containing H2-water (H2 + DSS) are shown. (B) The measurement of mean ± SD of colon length in each group at Day-7 is depicted. **p < 0.01: Value differs significantly between the groups indicated by brackets (t-test).