"Nicotinamide adenine dinucleotide attenuates acetaminophen-induced acute liver injury via activation of PARP1, Sirt1, and Nrf2 in mice"

作者全名："Liao, Cuiting; Zhang, Li; Jiang, Rong; Hu, Da; Xu, Juanjuan; Hu, Kai; Jiang, Shifang; Li, Longhui; Yang, Yongqiang; Huang, Jiayi; Tang, Li; Li, Longjiang"

作者地址："[Liao, Cuiting; Zhang, Li; Jiang, Rong; Hu, Da; Xu, Juanjuan; Hu, Kai; Jiang, Shifang; Yang, Yongqiang; Huang, Jiayi; Tang, Li; Li, Longjiang] Chongqing Med Univ, Basic Med Coll, Dept Pathophysiol, Chongqing 400016, Peoples R China; [Liao, Cuiting; Zhang, Li; Jiang, Rong; Hu, Da; Xu, Juanjuan; Hu, Kai; Jiang, Shifang; Yang, Yongqiang; Huang, Jiayi; Tang, Li; Li, Longjiang] Chongqing Med Univ, Lab Stem Cell & Tissue Engn, Chongqing 400016, Peoples R China; [Li, Longhui] Univ Chinese Acad Sci, Chongqing Gen Hosp, Ctr Hlth Management, Chongqing 400000, Peoples R China"

通信作者："Li, LJ (通讯作者)，Chongqing Med Univ, Basic Med Coll, Dept Pathophysiol, Chongqing 400016, Peoples R China.; Li, LJ (通讯作者)，Chongqing Med Univ, Lab Stem Cell & Tissue Engn, Chongqing 400016, Peoples R China."

来源：CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000860194800001

JCR分区：Q3

影响因子：2.1

年份：2022

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文献类型：Article; Early Access

关键词：acetaminophen; nicotinamide adenine dinucleotide; PARP1; Sirt1; Nrf2

摘要："The aim of this study was to investigate the protective effect of nicotinamide adenine dinucleotide (NAD+) against acute liver injury (ALI) induced by acetaminophen (APAP) overdose in mice. First, serum transaminases were used to assess the protective effect of NAD(+), and the data revealed that NAD(+) mitigated the APAP-induced ALI in a dose-dependent manner. Then, we per-formed hematoxylin-eosin staining of liver tissues and found that NAD+ alleviated the abnormalities of histopathology. Mean-while, increase in the malondialdehyde content and decrease in glutathione, superoxide dismutase (SOD), and glutathione peroxidase were identified in the APAP group, which were partially prevented by the NAD+ pretreatment. Moreover, compared with the mice treated with APAP only, the expression of poly ADP-ribose polymerase 1 (PARP1), Sirtuin1 (Sirt1), SOD2, nuclear factor erythroid 2-related factor 2 (Nrf2), and hemoxygenase-1 was upregulated, while Kelch-like ECH-associated protein 1 and histone H2AX phosphorylated on Ser-139 were downregulated by NAD(+ )in NAD(+) + APAP group. Conversely, NAD+ could not correct the elevated expression of phospho-Jun N-terminal kinase and phospho-extracellular signal-regulated kinase induced by APAP. Taken together, these findings suggest that NAD+ confers an anti-ALI effect to enhance the expression of PARP1 and Sirt1, and to simultaneously stimulate the Nrf2 anti-oxidant signaling pathway."

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