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Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering pKCδ/Nrf2 signaling pathway and inhibiting CYp 2e1

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Food Science and Human Wellness 2024年第2期13卷 932-945页

作者： Si Zou Yetao Gong Xiujie Li Yanbin Wu Jinzhong Wu Jianguo Wu Ka-Hing Wong College of pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Research Institute for Future Food The Hong Kong Polytechnic UniversityHong Kong 999077China Department of Food Science and Nutrition The Hong Kong Polytechnic UniversityHong Kong 999077China

Selenium nanoparticles(SeNps)have been demonstrated potential for use in diseases associated with oxidative *** SeNps with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application ***,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 *** elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also *** results showed that pTR-SeNps could significantly ameliorate ApAp-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting ***-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 ***,pTR-SeNps suppressed the biotransformation of ApAp to generate intracellular ROS through CYp 2e1 inhibition,restoring the mitochondrial ***,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 *** a potential hepatic protectant,pTR-SeNps could serve as a new source of selenium supplement for health-promoting and biomedical applications.

关键词： pTR-SeNps(polysaccharide-proteincomplex functionalized selenium nanoparticles) Acetaminophen-induced hepatotoxicity Nuclear factor erythroid 2-related factor 2 cytochrome p450 enzyme 2e1 Mitochondria

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