論文 - 詳細
RRC ID | 70518 |
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著者 | Enomoto M, Kaji K, Nishimura N, Fujimoto Y, Murata K, Takeda S, Tsuji Y, Fujinaga Y, Takaya H, Kawaratani H, Namisaki T, Akahane T, Yoshiji H. |
タイトル | Rifaximin and lubiprostone mitigate liver fibrosis development by repairing gut barrier function in diet-induced rat steatohepatitis. |
ジャーナル | Dig Liver Dis |
Abstract |
BACKGROUND:Although gut-derived lipopolysaccharide (LPS) affects the progression of non-alcoholic steatohepatitis (NASH) pathogenesis, few studies have focused on this relationship to develop treatments for NASH. AIMS:To explore the effects of combination with rifaximin and lubiprostone on NASH liver fibrosis through the modulation of gut barrier function. METHODS:To induce steatohepatitis, F344 rats were fed a choline-deficient l-amino acid-defined (CDAA) diet for 12 weeks and received oral administration of rifaximin and/or lubiprostone. Histological, molecular, and fecal microbial analyses were performed. Barrier function in Caco-2 cells were assessed by in vitro assays. RESULTS:Combination rifaximin/lubiprostone treatment significantly suppressed macrophage expansion, proinflammatory responses, and liver fibrosis in CDAA-fed rats by blocking hepatic translocation of LPS and activation of toll-like receptor 4 signaling. Rifaximin and lubiprostone improved intestinal permeability via restoring tight junction proteins (TJPs) with the intestinal activation of pregnane X receptor and chloride channel-2, respectively. Moreover, this combination increased the abundance of Bacteroides, Lactobacillus, and Faecalibacterium as well as decreased that of Veillonella resulting in an increase of fecal short-chain fatty acids and a decrease of intestinal sialidase activity. Both agents also directly suppressed the LPS-induced barrier dysfunction and depletion of TJPs in Caco-2 cells. CONCLUSION:The combination of rifaximin and lubiprostone may provide a novel strategy for treating NASH-related fibrosis. |
巻・号 | 54(10) |
ページ | 1392-1402 |
公開日 | 2022-10-1 |
DOI | 10.1016/j.dld.2022.04.012 |
PII | S1590-8658(22)00257-2 |
PMID | 35514019 |
MeSH | Acetamides Amino Acids / metabolism Amino Acids / pharmacology Animals Caco-2 Cells Chloride Channels / metabolism Chloride Channels / pharmacology Choline / metabolism Choline / pharmacology Diet Humans Lipopolysaccharides / metabolism Liver / pathology Liver Cirrhosis / complications Liver Cirrhosis / prevention & control Lubiprostone / pharmacology Neuraminidase / metabolism Neuraminidase / pharmacology Non-alcoholic Fatty Liver Disease* / drug therapy Non-alcoholic Fatty Liver Disease* / etiology Non-alcoholic Fatty Liver Disease* / metabolism Pregnane X Receptor / metabolism Rats Rats, Inbred F344 Rifaximin / pharmacology Tight Junction Proteins / metabolism Toll-Like Receptor 4 / metabolism |
IF | 3.57 |
リソース情報 | |
ヒト・動物細胞 | CACO-2(RCB0988) |