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Disruption of small intestinal mucosal homeostasis in mice with amiodarone induced steatohepatitis
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Disruption of small intestinal mucosal homeostasis in mice with amiodarone induced steatohepatitis
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Journal Article
Disruption of small intestinal mucosal homeostasis in mice with amiodarone induced steatohepatitis
2025
Overview
In the current study, we sought to investigate the pathogenesis of amiodarone (AMD)-induced steatohepatitis, focusing on the pathological changes in the small intestine and liver. The association between patients taking AMD and metabolic dysfunction-associated steatohepatitis (MASH) was analyzed using the Japanese Adverse Drug Event Report (JADER) database. Barrier functions, such as crypt-villus architecture, mucosal permeability, and intestinal microbiota composition, were analyzed in a mouse model of AMD-induced steatohepatitis. The JADER database revealed positive signals for MASH in patients taking AMD. AMD induced lipid accumulation and inflammation,
Tnf
mRNA expression, and F4/80
+
CD14
+
cell infiltration in the mouse liver. Villus shortening, changes in the localization of tight junction proteins, increased mucosal permeability, and altered intestinal microbiota were observed in the small intestines of AMD-treated mice. Moreover, the localization of leucine-rich repeat-containing G-protein coupled receptor (Lgr) 5
+
and the Wnt/β-catenin signaling pathway was impaired in the small intestines of these mice. Lgr 5
+
crypt base columnar stem cells, which are regulated by the Wnt/β-catenin signaling pathway, play an important role in intestinal mucosal homeostasis. Our data suggest that intestinal homeostasis is disrupted in AMD-induced MASH, which provides important insights into the development of therapeutic approaches for difficult-to-treat drug-induced MASH.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Amiodarone - adverse effects
/ Animals
/ Drugs
/ Fatty Liver - chemically induced
/ Gastrointestinal Microbiome - drug effects
/ Humanities and Social Sciences
/ Humans
/ Intestinal Mucosa - drug effects
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Intestine, Small - drug effects
/ Intestine, Small - metabolism
/ Intestine, Small - pathology
/ JADER
/ Liver
/ Male
/ Mice
/ Mucosa
/ Plasma
/ Science
/ Villus
/ Wnt Signaling Pathway - drug effects
