Decompensated MASH-Cirrhosis Model by Acute and Toxic Effects of Phenobarbital.

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  • Additional Information
    • Corporate Authors:
      DECISION
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI
    • Subject Terms:
      Phenobarbital* ; Disease Models, Animal* ; Carbon Tetrachloride*/toxicity ; Liver Cirrhosis*/chemically induced ; Liver Cirrhosis*/pathology; Animals ; Rats ; Male ; Fatty Liver/chemically induced ; Fatty Liver/pathology ; Liver/drug effects ; Liver/pathology ; Liver/metabolism ; Diet, High-Fat/adverse effects
    • Abstract:
      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 (CCl 4 ) 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 CCl 4 intoxication and WD represents a fast and reproducible rat model mimicking decompensated MASH-cirrhosis in humans. Thus, CCl 4 + WD with LT low-dose phenobarbital treatment might be the preferred rat animal model for drug development in MASH-cirrhosis.
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    • Grant Information:
      403224013 DFG; DEEP-HCC BMBF; ENABLE, ACLF-I HMWK; 12350 Eurostars; ANR-20- CE14-0038 ANR-IMAGINE; Equipe FRM EQU202203014642 Fondation pour la Recherche Médicale; FRM EQU202303016287 Fondation pour la Recherche Médicale; ATIP AVENIR Institut National de la Santé et de la Recherche Médicale; ANR-18-CE14-0006-01, RHU QUID-NASH, ANR-18-IDEX-0001, ANR-22-CE14-0002 Agence Nationale pour la Recherche; 847949 European Union's Horizon 2020 research and innovation programme; MCIN/AEI, PID2022-138970OB-I00 10.13039/501100011033/FEDER Ministerio de Ciencia e Innovacion/Agencia Estatal Investigación; 825694 MICROB-PREDICT; 847949 DECISION; 668031 GALAXY; 731875 LIVERHOPE; 964590 IHMCSA
    • Contributed Indexing:
      Keywords: carbon tetrachloride (CCl4); high-fat and high-cholesterol Western diet (WD); long-term (LT); metabolic dysfunction-associated steatohepatitis (MASH); phenobarbital (PB); short-term (ST)
    • Accession Number:
      YQE403BP4D (Phenobarbital)
      CL2T97X0V0 (Carbon Tetrachloride)
    • Publication Date:
      Date Created: 20241025 Date Completed: 20241025 Latest Revision: 20241027
    • Publication Date:
      20241027
    • Accession Number:
      PMC11505720
    • Accession Number:
      10.3390/cells13201707
    • Accession Number:
      39451225