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Role of the lipid-regulated NF-κB/IL-6/STAT3 axis in alpha-naphthyl isothiocyanate-induced liver injury.
Fang, Zhong-Ze; Tanaka, Naoki; Lu, Dan; Jiang, Chang-Tao; Zhang, Wei-Hua; Zhang, Chunze; Du, Zuo; Fu, Zhi-Wei; Gao, Peng; Cao, Yun-Feng; Sun, Hong-Zhi; Zhu, Zhi-Tu; Cai, Yan; Krausz, Kristopher W; Yao, Zhi; Gonzalez, Frank J.
Afiliación
  • Fang ZZ; Department of Toxicology, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
  • Tanaka N; Laboratory of Metabolism, Center for Cancer Research, National Institutes of Health, Building 37, Room 3106, Bethesda, MD, 20892, USA.
  • Lu D; Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 30070, China.
  • Jiang CT; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and The First Affiliated Hospital of Liaoning Medical University, No. 457, Zhongshan Road, Dalian, 116023, China.
  • Zhang WH; Key Laborotary of Liaoning Tumor Clinical Metabolomics (KLLTCM), Jinzhou, Liaoning, China.
  • Zhang C; Laboratory of Metabolism, Center for Cancer Research, National Institutes of Health, Building 37, Room 3106, Bethesda, MD, 20892, USA.
  • Du Z; Department of Metabolic Regulation, Shinshu University Graduate School of Medicine, Matsumoto, 390-8621, Japan.
  • Fu ZW; Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, 30070, China.
  • Gao P; Laboratory of Metabolism, Center for Cancer Research, National Institutes of Health, Building 37, Room 3106, Bethesda, MD, 20892, USA.
  • Cao YF; Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, 300121, China.
  • Sun HZ; Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, 300121, China.
  • Zhu ZT; Department of Toxicology, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
  • Cai Y; Department of Toxicology, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin, 300070, China.
  • Krausz KW; Key Laborotary of Liaoning Tumor Clinical Metabolomics (KLLTCM), Jinzhou, Liaoning, China.
  • Yao Z; Clinical Laboratory, Dalian Sixth People's Hospital, Dalian, 116031, China.
  • Gonzalez FJ; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and The First Affiliated Hospital of Liaoning Medical University, No. 457, Zhongshan Road, Dalian, 116023, China.
Arch Toxicol ; 91(5): 2235-2244, 2017 May.
Article en En | MEDLINE | ID: mdl-27853831
Alpha-naphthyl isothiocyanate (ANIT)-induced liver damage is regarded as a useful model to study drug-induced cholestatic hepatitis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based metabolomics revealed clues to the mechanism of ANIT-induced liver injury, which facilitates the elucidation of drug-induced liver toxicity. 1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:0) and 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:1) were significantly increased in serum from ANIT-treated mice, and this increase resulted from altered expression of genes encoding the lipid metabolism enzymes Chka and Scd1. ANIT also increased NF-κB/IL-6/STAT3 signaling, and in vitro luciferase reporter gene assays revealed that LPC 18:0 and LPC 18:1 can activate NF-κB in a concentration-dependent manner. Activation of PPARα through feeding mice a Wy-14,643-containing diet (0.1%) reduced ANIT-induced liver injury, as indicated by lowered ALT and AST levels, and liver histology. In conclusion, the present study demonstrated a role for the lipid-regulated NF-κB/IL-6/STAT3 axis in ANIT-induced hepatotoxicity, and that PPARα may be a potential therapeutic target for the prevention of drug-induced cholestatic liver injury.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: FN-kappa B / Interleucina-6 / Factor de Transcripción STAT3 / Enfermedad Hepática Inducida por Sustancias y Drogas / 1-Naftilisotiocianato Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Arch Toxicol Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: FN-kappa B / Interleucina-6 / Factor de Transcripción STAT3 / Enfermedad Hepática Inducida por Sustancias y Drogas / 1-Naftilisotiocianato Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Arch Toxicol Año: 2017 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania