{
    "abstract": "Small-for-size syndrome (SFSS) looms over patients needing liver resection or living-donor transplantation. Hypoxia has been shown to be crucial for the successful outcome of liver resection in the very early postoperative phase. While poorly acceptable as such in real-world clinical practice, hypoxia responses can still be simulated by pharmacologically raising levels of its transducers, the hypoxia-inducible factors (HIFs). We aimed to assess the potential role of a selective inhibitor of HIF degradation in 70% hepatectomy (70%Hx).\nIn a pilot study, we tested the required dose of roxadustat to stabilize liver HIF1\u03b1. We then performed 70%Hx in 8-week-old male Lewis rats and administered 25 mg/kg of roxadustat (RXD25) at the end of the procedure. Regeneration was assessed: ki67 and 5-ethynyl-2'-deoxyuridine (EdU) immunofluorescent labeling, and histological parameters. We also assessed liver function via a blood panel and functional gadoxetate-enhanced magnetic resonance imaging (MRI), up to 47 h after the procedure. Metabolic results were analyzed by means of RNA sequencing (RNAseq).\nRoxadustat effectively increased early HIF1\u03b1 transactivity. Liver function did not appear to be improved nor liver regeneration to be accelerated by the experimental compound. However, treated livers showed a mitigation in hepatocellular steatosis and ballooning, known markers of cellular stress after liver resection. RNAseq confirmed that roxadustat unexpectedly increases lipid breakdown and cellular respiration.\nSelective HIF stabilization did not result in an enhanced liver function after standard liver resection, but it induced interesting metabolic changes that are worth studying for their possible role in extended liver resections and fatty liver diseases.",
    "authors": [
        {
            "affiliation": "P\u00f4le de Chirurgie Exp\u00e9rimentale et Transplantation, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium.\nDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.\nLiver Transplantation, Service de Chirurgie G\u00e9n\u00e9rale et Transplantation Abdominale, Cliniques Universitaires Saint-Luc, Brussels, Belgium.\nKidney Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.",
            "firstname": "Samuele",
            "initials": "S",
            "lastname": "Iesari"
        },
        {
            "affiliation": "Laboratory of Hepato-Gastroenterology, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium.",
            "firstname": "Isabelle",
            "initials": "I",
            "lastname": "Leclercq"
        },
        {
            "affiliation": "Nuclear and Electron Spin Technologies, Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain, Brussels, Belgium.",
            "firstname": "Nicolas",
            "initials": "N",
            "lastname": "Joudiou"
        },
        {
            "affiliation": "Department of Pathology, Keio University, Tokyo, Japan.",
            "firstname": "Mina",
            "initials": "M",
            "lastname": "Komuta"
        },
        {
            "affiliation": "IREC Imaging Platform, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium.",
            "firstname": "Aur\u00e9lie",
            "initials": "A",
            "lastname": "Daumerie"
        },
        {
            "affiliation": "Centre for Applied Molecular Technologies, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium.",
            "firstname": "J\u00e9r\u00f4me",
            "initials": "J",
            "lastname": "Ambroise"
        },
        {
            "affiliation": "Laboratory of Hepato-Gastroenterology, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium.",
            "firstname": "Alexandra",
            "initials": "A",
            "lastname": "Dili"
        },
        {
            "affiliation": "Laboratory of Hepato-Gastroenterology, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium.",
            "firstname": "Natacha",
            "initials": "N",
            "lastname": "Feza-Bingi"
        },
        {
            "affiliation": "P\u00f4le de Chirurgie Exp\u00e9rimentale et Transplantation, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium.",
            "firstname": "Daela",
            "initials": "D",
            "lastname": "Xhema"
        },
        {
            "affiliation": "IREC Imaging Platform, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium.",
            "firstname": "Caroline",
            "initials": "C",
            "lastname": "Bouzin"
        },
        {
            "affiliation": "Nuclear and Electron Spin Technologies, Louvain Drug Research Institute, Universit\u00e9 catholique de Louvain, Brussels, Belgium.",
            "firstname": "Bernard",
            "initials": "B",
            "lastname": "Gallez"
        },
        {
            "affiliation": "Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.",
            "firstname": "Francesco",
            "initials": "F",
            "lastname": "Pisani"
        },
        {
            "affiliation": "P\u00f4le de Chirurgie Exp\u00e9rimentale et Transplantation, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium.\nLiver Transplantation, Service de Chirurgie G\u00e9n\u00e9rale et Transplantation Abdominale, Cliniques Universitaires Saint-Luc, Brussels, Belgium.",
            "firstname": "Eliano",
            "initials": "E",
            "lastname": "Bonaccorsi-Riani"
        },
        {
            "affiliation": "P\u00f4le de Chirurgie Exp\u00e9rimentale et Transplantation, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium.",
            "firstname": "Pierre",
            "initials": "P",
            "lastname": "Gianello"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.",
    "doi": "10.1042/CS20210183",
    "journal": "Clinical science (London, England : 1979)",
    "keywords": [
        "hepatocellular ballooning",
        "hepatocellular steatosis",
        "hypoxia-inducible factors",
        "liver regeneration",
        "liver resection",
        "prolyl hydroxylase domain protein inhibitors"
    ],
    "methods": null,
    "publication_date": "2021-09-23",
    "pubmed_id": "34550341",
    "results": "Roxadustat effectively increased early HIF1\u03b1 transactivity. Liver function did not appear to be improved nor liver regeneration to be accelerated by the experimental compound. However, treated livers showed a mitigation in hepatocellular steatosis and ballooning, known markers of cellular stress after liver resection. RNAseq confirmed that roxadustat unexpectedly increases lipid breakdown and cellular respiration.",
    "title": "Selective HIF stabilization alleviates hepatocellular steatosis and ballooning in a rodent model of 70% liver resection.",
    "xml": "<Element 'PubmedArticle' at 0x788505937920>"
}