Methane Alleviates Inflammation and Apoptosis of Dextran Sulfate Sodium-Induced Inflammatory Bowel Diseases by Inhibiting Toll-Like Receptor 4 (TLR4)/Myeloid Differentiation Factor 88 (MyD88)/Nuclear Translocation of Nuclear Factor-κB (NF-κB) and Endoplasmic Reticulum Stress Pathways in Mice.

BACKGROUND Inflammatory bowel diseases (IBDs) are chronic idiopathic diseases with increased occurrence and recurrence rates. The aim of this study was to explore whether methane-rich saline (MRS) would be beneficial to IBD. MATERIAL AND METHODS Dextran sulfate sodium (DSS) was utilized to establish an IBD model. Male C57BL/6J mice were randomly grouped as follows: the control group, the DSS+NS group, the DSS+5-ASA group, the DSS+MRS (1) and DSS+MRS (10) groups. Seven days after model induction, blood and colon tissues were collected to assess the treatment effects. RESULTS The DSS+MRS (10) group showed obviously reduced weight loss, disease activity index, and spleen index. The isolated colon samples had a notably longer length, less thickness and weight, and better macroscopic score with MRS treatment compared with the DSS+NS group. Additionally, assessment of morphological impairment revealed a milder and lower microscopic score in the DSS+MRS (10) group, consistent with the myeloperoxidase (MPO) results. The inflammation-related molecules levels were dramatically reduced by MRS. MRS also significantly reduced oxidative stress related proteins. In addition, apoptotic cells were visually decreased in the DSS+MRS (10) group, in which the pro-apoptotic molecules Bax and cleaved caspase-3 were reduced, whereas the level of Bcl-2 was increased. Furthermore, MRS markedly decreased the TLR4, MyD88, p-NF-kappaB p65, p-IKKalphaß, and p-IkappaBalpha, and increased IL-10, p-JAK1, and p-STAT3 expression levels. Proteins involved in endoplasmic reticulum stress (ERS) were also notably reduced under MRS treatment. CONCLUSIONS MRS exerts protective effects on DSS-induced IBD via inhibiting inflammatory reaction, promoting anti-inflammatory capacity, suppressing oxidative stress, and ameliorating apoptosis.