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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.<\/jats:p>","DOI":"10.3390\/cells13201707","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T09:14:48Z","timestamp":1729242888000},"page":"1707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decompensated MASH-Cirrhosis Model by Acute and Toxic Effects of Phenobarbital"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5162-1048","authenticated-orcid":false,"given":"Nico","family":"Kraus","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Hospital of the Goethe University, 60596 Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank Erhard","family":"Uschner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Hospital of the Goethe University, 60596 Frankfurt, Germany"},{"name":"Department of Internal Medicine B, University Clinic M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magnus","family":"Moeslein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Hospital of the Goethe University, 60596 Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2195-3666","authenticated-orcid":false,"given":"Robert","family":"Schierwagen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Hospital of the Goethe University, 60596 Frankfurt, Germany"},{"name":"Department of Internal Medicine B, University Clinic M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyi","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Hospital of the Goethe University, 60596 Frankfurt, Germany"},{"name":"Department of Internal Medicine B, University Clinic M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian Joseph","family":"Brol","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Hospital of the Goethe University, 60596 Frankfurt, Germany"},{"name":"Department of Internal Medicine B, University Clinic M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eike","family":"F\u00fcrst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine B, University Clinic M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inga","family":"Gr\u00fcnewald","sequence":"additional","affiliation":[{"name":"Gerhard-Domagk-Institute of Pathology, University Clinic Muenster, 48149 M\u00fcnster, 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