食品科学与人类健康(英文)2024,Vol.13Issue(2) :932-945.DOI:10.26599/FSHW.2022.9250080

Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1

Si Zou Yetao Gong Xiujie Li Yanbin Wu Jinzhong Wu Jianguo Wu Ka-Hing Wong
食品科学与人类健康(英文)2024,Vol.13Issue(2) :932-945.DOI:10.26599/FSHW.2022.9250080

Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1

Si Zou 1Yetao Gong 1Xiujie Li 1Yanbin Wu 1Jinzhong Wu 1Jianguo Wu 1Ka-Hing Wong2
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作者信息

  • 1. College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China
  • 2. Research Institute for Future Food,The Hong Kong Polytechnic University,Hong Kong 999077,China;Department of Food Science and Nutrition,The Hong Kong Polytechnic University,Hong Kong 999077,China
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Abstract

Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.

Key words

PTR-SeNPs(polysaccharide-protein complex/functionalized selenium nanoparticles)/Acetaminophen-induced hepatotoxicity/Nuclear factor erythroid 2-related factor 2/Cytochrome P450 enzyme 2E1/Mitochondria

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基金项目

国家自然科学基金(81700524)

Natural Science Foundation of Fujian Province from Fujian Provincial Department of Science and Technology(2022J01866)

Key Project of Fujian University of Traditional Chinese Medicine(X2021019)

Collaborative Innovation and Platform Establishment Project of Department of Science and Technology of Guangdong Province(2019A050520003)

出版年

2024
食品科学与人类健康(英文)

食品科学与人类健康(英文)

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