| Autor: |
Hiroki Yanagisawa, Hitoshi Maeda, Isamu Noguchi, Motohiko Tanaka, Naoki Wada, Taisei Nagasaki, Kazuki Kobayashi, Gai Kanazawa, Kazuaki Taguchi, Victor Tuan Giam Chuang, Hiromi Sakai, Hiroyuki Nakashima, Manabu Kinoshita, Hiroaki Kitagishi, Yasuko Iwakiri, Yutaka Sasaki, Yasuhito Tanaka, Masaki Otagiri, Hiroshi Watanabe, Toru Maruyama |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Redox Biology, Vol 76, Iss , Pp 103314- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2024.103314 |
| Popis: |
Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of nonalcoholic fatty liver disease characterised by fat accumulation, inflammation, oxidative stress, fibrosis, and impaired liver regeneration. In this study, we found that heme oxygenase-1 (HO-1) is induced in both MASH patients and in a MASH mouse model. Further, hepatic carbon monoxide (CO) levels in MASH model mice were >2-fold higher than in healthy mice, suggesting that liver HO-1 is activated as MASH progresses. Based on these findings, we used CO-loaded red blood cells (CO-RBCs) as a CO donor in the liver, and evaluated their therapeutic effect in methionine-choline deficient diet (MCDD)-induced and high-fat-diet (HFD)-induced MASH model mice. Intravenously administered CO-RBCs effectively delivered CO to the MASH liver, where they prevented fat accumulation by promoting fatty acid oxidation via AMP-activated protein kinase (AMPK) activation and peroxisome proliferator-activated receptor induction. They also markedly suppressed Kupffer cell activation and their corresponding anti-inflammatory and antioxidative stress activities in MASH mice. CO-RBCs also helped to restore liver regeneration in mice with HFD-induced MASH by activating AMPK. We confirmed the underlying mechanisms by performing in vitro experiments in RAW264.7 cells and palmitate-stimulated HepG2 cells. Taken together, CO-RBCs show potential as a promising cellular treatment for MASH. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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