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NMNATs expression inhibition mediated NAD+ deficiency plays a critical role in doxorubicin-induced hepatotoxicity in mice.
Cheng, Fang; Zhang, Yongtai; Xiong, Hongli; Zhao, Minzhu; Wang, Qi; Zhu, Ying; Li, Yongguo; Tang, Renkuan; Li, Jianbo.
Afiliação
  • Cheng F; Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, PR China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing, PR China; Chongqing Key Laboratory of Forensic Medicine, Chongqing, PR China.
  • Zhang Y; Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, PR China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing, PR China; Chongqing Key Laboratory of Forensic Medicine, Chongqing, PR China.
  • Xiong H; Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, PR China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing, PR China; Chongqing Key Laboratory of Forensic Medicine, Chongqing, PR China.
  • Zhao M; Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, PR China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing, PR China; Chongqing Key Laboratory of Forensic Medicine, Chongqing, PR China.
  • Wang Q; Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, PR China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing, PR China; Chongqing Key Laboratory of Forensic Medicine, Chongqing, PR China.
  • Zhu Y; Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, PR China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing, PR China; Chongqing Key Laboratory of Forensic Medicine, Chongqing, PR China.
  • Li Y; Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, PR China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing, PR China; Chongqing Key Laboratory of Forensic Medicine, Chongqing, PR China.
  • Tang R; Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, PR China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing, PR China; Chongqing Key Laboratory of Forensic Medicine, Chongqing, PR China.
  • Li J; Department of Forensic Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, PR China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing, PR China; Chongqing Key Laboratory of Forensic Medicine, Chongqing, PR China. Electronic addre
Toxicol Appl Pharmacol ; 482: 116799, 2024 01.
Article em En | MEDLINE | ID: mdl-38160893
ABSTRACT
Doxorubicin (DOX) is one of the most widely used antineoplastic drugs with known cardiotoxicity while other organ toxicity, such as hepatotoxicity is not well defined. This study was to explore the role of nicotinamide adenine dinucleotide (NAD+) in DOX-induced hepatotoxicity. DOX (20 mg/kg) induced acute liver injury and oxidative stress in C57BL/6 J mice at 48 h. Notably, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H dehydrogenase quinone 1 (NQO1) were downregulated. NAD+ deficiency was confirmed due to DOX exposure. Mechanistically, the downregulation of nicotinamide mononucleotide adenylyl transferase 1 (NMNAT1), NMNAT2 and NMNAT3, while no alteration of nicotinamide phosphoribosyl transferase was proved. As a consequence of NAD+ deficiency, the expression of poly-ADP-ribose polymerase1 (PARP1), CD38 and Sirtuin1 (SIRT1) were reduced. Furthermore, supplementation of NAD+ (200 mg/kg/day) or its precursor nicotinamide mononucleotide (NMN) (500 mg/kg/day) alleviated liver injury, attenuated oxidative stress, and elevated the downregulation of Nrf2 and NQO1. More importantly, compromised expression of NMNAT1-3, PARP1, CD38 and SIRT1 were improved by NAD+ and NMN. In conclusion, NAD+ deficiency due to NMNATs expression inhibition may attribute to the pathogenesis of DOX-induced hepatotoxicity, thus providing new insights for mitigating DOX side effects.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença Hepática Induzida por Substâncias e Drogas / NAD Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença Hepática Induzida por Substâncias e Drogas / NAD Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article