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886995.pdf (30.74 MB)

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Data de publicació

2024

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cc-by (c) Kraus N et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/220281

Decompensated MASH-cirrhosis model by acute and toxic effects of phenobarbital.

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Recurs relacionat

https://doi.org/10.3390/cells13201707

Resum

Metabolic dysfunction-associated Steatohepatitis (MASH), is a prominent cause for liver cirrhosis. MASH-cirrhosis is responsible for liver complications and there is no specific treatment. To develop new therapeutic approaches, animal models are needed. The aim of this study was to develop a fast animal model of MASH-cirrhosis in rats reflecting the human disease. Carbon tetrachloride (CCl4) injections in combination with a high-fat Western diet (WD) were used to induce MASH-cirrhosis. To accelerate liver injury, animals received phenobarbital (PB) in their drinking water using two different regimens. Rats developed advanced MASH-cirrhosis characterized by portal hypertension, blood biochemistry, hepatic ballooning, steatosis, inflammation and fibrosis. Importantly, rats receiving low-dose PB for the long term (LT) showed ascites after 6 weeks, whereas rats with high-dose short-term (ST) PB developed ascites after 8 weeks. ST- and LT-treated rats showed increased portal pressure (PP) and decreased mean arterial pressure (MAP). Of note, hepatocyte ballooning was only observed in the LT group. The LT administration of low-dose PB with CCl4 intoxication and WD represents a fast and reproducible rat model mimicking decompensated MASH-cirrhosis in humans. Thus, CCl4 + WD with LT low-dose phenobarbital treatment might be the preferred rat animal model for drug development in MASH-cirrhosis.

Matèries

Malalties del fetge, Hipercolesterolèmia, Cirrosi hepàtica

Matèries (anglès)

Liver diseases, Hypercholesteremia, Hepatic cirrhosis

Citació

Col·leccions

Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

GRÜNEWALD, Inga, et al. Decompensated MASH-cirrhosis model by acute and toxic effects of phenobarbital. Cells. 2024. Vol. 13, num. 20. ISSN 2073-4409. [consulted: 3 of August of 2026]. Available at: https://hdl.handle.net/2445/220281

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