Arsenic trioxide preconditioning attenuates hepatic ischemia- reperfusion injury in mice: Role of ERK/AKT and autophagy
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Le résumé fourni par la source
BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION: Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Arsenic trioxide preconditioning attenuates hepatic ischemia- reperfusion injury in mice: Role of ERK/AKT and autophagy
- Date Crossref
- 17/01/2025
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Army Medical University Department of Hepatobiliary Surgery pays non établi dans la noticeUniversité ou école supérieure
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Harbin Medical University Key Laboratory of Hepatosplenic Surgery pays non établi dans la noticeUniversité ou école supérieure
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Dalian Medical University pays non établi dans la noticeUniversité ou école supérieure
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Second Affiliated Hospital of Chongqing Medical University pays non établi dans la noticeÉtablissement de santé
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First Affiliated Hospital of Harbin Medical University pays non établi dans la noticeÉtablissement de santé
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Chongqing Medical University pays non établi dans la noticeUniversité ou école supérieure
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The Affiliated Hospital of Inner Mongolia Minzu University Key Laboratory of Hepatosplenic Surgery pays non établi dans la noticeUniversité ou école supérieure
Department of Hepatobiliary Surgery — Army Medical University, Key Laboratory of Hepatosplenic Surgery — Harbin Medical University et Dalian Medical University, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.