{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T18:15:36Z","timestamp":1769883336589,"version":"3.49.0"},"reference-count":31,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002915","name":"the \u201cFondation pour la Recherche M\u00e9dicale\u201d (FRM)","doi-asserted-by":"publisher","award":["DEQ20180339216"],"award-info":[{"award-number":["DEQ20180339216"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Some life-threatening acute hepatitis originates from drug-induced liver injury (DILI). Carbon tetrachloride (CCl4)-induced acute liver injury in mice is the widely used model of choice to study acute DILI, which pathogenesis involves a complex interplay of oxidative stress, necrosis, and apoptosis. Since the receptor interacting protein kinase-1 (RIPK1) is able to direct cell fate towards survival or death, it may potentially affect the pathological process of xenobiotic-induced liver damage. Two different mouse lines, either deficient for Ripk1 specifically in liver parenchymal cells (Ripk1LPC-KO) or for the kinase activity of RIPK1 (Ripk1K45A, kinase dead), plus their respective wild-type littermates (Ripk1fl\/fl, Ripk1wt\/wt), were exposed to single toxic doses of CCl4. This exposure led in similar injury in Ripk1K45A mice and their littermate controls. However, Ripk1LPC-KO mice developed more severe symptoms with massive hepatocyte apoptosis as compared to their littermate controls. A pretreatment with a TNF-\u03b1 receptor decoy exacerbated liver apoptosis in both Ripk1fl\/fl and Ripk1LPC-KO mice. Besides, a FasL antagonist promoted hepatocyte apoptosis in Ripk1fl\/fl mice but reduced it in Ripk1LPC-KO mice. Thus, the scaffolding properties of RIPK1 protect hepatocytes from apoptosis during CCl4 intoxication. TNF-\u03b1 and FasL emerged as factors promoting hepatocyte survival. These protective effects appeared to be independent of RIPK1, at least in part, for TNF-\u03b1, but dependent on RIPK1 for FasL. These new data complete the deciphering of the molecular mechanisms involved in DILI in the context of research on their prevention or cure.<\/jats:p>","DOI":"10.3390\/ijms23137367","type":"journal-article","created":{"date-parts":[[2022,7,3]],"date-time":"2022-07-03T22:50:46Z","timestamp":1656888646000},"page":"7367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["RIPK1 in Liver Parenchymal Cells Limits Murine Hepatitis during Acute CCl4-Induced Liver Injury"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8636-8644","authenticated-orcid":false,"given":"Huma","family":"Hameed","sequence":"first","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement ET Travail)\u2013UMR_S 1085, F-35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8771-3219","authenticated-orcid":false,"given":"Muhammad","family":"Farooq","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement ET Travail)\u2013UMR_S 1085, F-35000 Rennes, France"},{"name":"Department of Clinical Sciences, College of Veterinary and Animal Sciences, Jhang 35200, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9line","family":"Vuillier","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement ET Travail)\u2013UMR_S 1085, F-35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Piquet-Pellorce","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement ET Travail)\u2013UMR_S 1085, F-35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna\u00efg","family":"Hamon","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement ET Travail)\u2013UMR_S 1085, F-35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Th\u00e9r\u00e8se","family":"Dimanche-Boitrel","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement ET Travail)\u2013UMR_S 1085, F-35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Samson","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement ET Travail)\u2013UMR_S 1085, F-35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1118-3311","authenticated-orcid":false,"given":"Jacques","family":"Le Seyec","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement ET Travail)\u2013UMR_S 1085, F-35000 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8651","DOI":"10.21037\/apm-21-981","article-title":"Global research trends of drug-induced liver injury (DILI) in the past two decades: A bibliometric and visualized study","volume":"10","author":"Liang","year":"2021","journal-title":"Ann. 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