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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/4095

Title: Rifaximin enhances the L‑carnitine‑mediated preventive effects on skeletal muscle atrophy in cirrhotic rats by modulating the gut‑liver‑muscle axis
Other Titles: リファキシミンは腸-肝臓-筋肉軸の調節により肝硬変ラットの骨格筋萎縮に対するL-カルニチンを介した予防効果を増強する
Authors: Murata, Koji
Kaji, Kosuke
Nishimura, Norihisa
Enomoto, Masahide
Fujimoto, Yuki
Takeda, Soichi
Tsuji, Yuki
Fujinaga, Yukihisa
Takaya, Hiroaki
Kawaratani, Hideto
Namisaki, Tadashi
Akahane, Takemi
Yoshiji, Hitoshi
Keywords: liver cirrhosis
sarcopenia
endotoxin
intestinal permeability
Issue Date: Aug-2022
Publisher: Spandidos Publications
Citation: International journal of molecular medicine Vol.50 No.2 Article No.101 (2022 Aug)
Abstract: The gut‑liver‑muscle axis is associated with the development of sarcopenia in liver cirrhosis. The present study aimed to illustrate the combined effects of rifaximin and L‑carnitine on skeletal muscle atrophy in cirrhotic rats with steatohepatitis. For this purpose, a total of 344 Fischer rats were fed a choline‑deficient L‑amino acid‑defined (CD AA) diet with the daily oral administration of rifaximin (100 mg/kg) and/or L‑carnitine (200 mg/kg), and measurements of psoas muscle mass index and forelimb grip strength were performed. After feeding for 12 weeks, blood samples, and liver, ileum and gastrocnemius muscle tissues were harvested. The effects of L‑carnitine on rat myocytes were assessed using in vitro assays. Treatment with rifaximin attenuated hyperammonemia and liver fibrosis in the CD AA‑fed rats. Moreover, it improved intestinal permeability with the restoration of tight junction proteins and suppressed the lipopolysaccharide (LPS)‑mediated hepatic macrophage activation and pro‑inflammatory response. In addition, rifaximin prevented skeletal muscle mass atrophy and weakness by decreasing intramuscular myostatin and pro‑inflammatory cytokine levels. Moreover, rifaximin synergistically enhanced the L‑carnitine‑mediated improvement of skeletal muscle wasting by promoting the production of insulin‑like growth factor‑1 and mitochondrial biogenesis, resulting in the inhibition of the ubiquitin‑proteasome system (UPS). The in vitro assays revealed that L‑carnitine directly attenuated the impairment of mitochondrial biogenesis, thereby inhibiting the UPS in rat myocytes that were stimulated with LPS or tumor necrosis factor‑α. On the whole, the present study demonstrates that the combination of rifaximin with L‑carnitine may provide a clinical benefit for liver cirrhosis‑related sarcopenia.
Description: 博士(医学)・甲第863号・令和5年3月15日
© Murata et al. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.
URI: http://hdl.handle.net/10564/4095
ISSN: 11073756
DOI: https://doi.org/10.3892/ijmm.2022.5157
Academic Degrees and number: 24601甲第863号
Degree-granting date: 2023-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2022年度

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