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05 June 2020 : Animal Research  

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

Naiying Shen1B, Zhixiang Wang1C, Cong Wang2E, Jingyao Zhang2A*, Chang Liu2A

DOI: 10.12659/MSM.922248

Med Sci Monit 2020; 26:e922248

Abstract

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-κB p65, p-IKKαβ, and p-IκBα, 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.

Keywords: Endoplasmic reticulum stress, Inflammatory Bowel Diseases, Toll-Like Receptor 4, Anti-Inflammatory Agents, Apoptosis, Dextran Sulfate, Methane, Mice, Inbred C57BL, Myeloid Differentiation Factor 88, NF-kappa B, Oxidative Stress, Random Allocation, Signal Transduction

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750