Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1
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 invest...
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Tsinghua University Press
2024-03-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | https://www.sciopen.com/article/10.26599/FSHW.2022.9250080 |
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| author | Si Zou Yetao Gong Xiujie Li Yanbin Wu Jinzhong Wu Jianguo Wu Ka-Hing Wong |
| author_facet | Si Zou Yetao Gong Xiujie Li Yanbin Wu Jinzhong Wu Jianguo Wu Ka-Hing Wong |
| author_sort | Si Zou |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-defc7ce819fe469b8d52d5972a6ea636 |
| institution | OA Journals |
| issn | 2213-4530 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-defc7ce819fe469b8d52d5972a6ea6362025-08-20T02:03:51ZengTsinghua University PressFood Science and Human Wellness2213-45302024-03-0113293294510.26599/FSHW.2022.9250080Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1Si Zou0Yetao Gong1Xiujie Li2Yanbin Wu3Jinzhong Wu4Jianguo Wu5Ka-Hing Wong6College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, ChinaCollege of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, ChinaCollege of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, ChinaCollege of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, ChinaCollege of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, ChinaCollege of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, ChinaResearch Institute for Future Food, The Hong Kong Polytechnic University, Hong Kong 999077, ChinaSelenium 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.https://www.sciopen.com/article/10.26599/FSHW.2022.9250080ptr-senps (polysaccharide-protein complex functionalized selenium nanoparticles)acetaminophen-induced hepatotoxicitynuclear factor erythroid 2-related factor 2cytochrome p450 enzyme 2e1mitochondria |
| spellingShingle | Si Zou Yetao Gong Xiujie Li Yanbin Wu Jinzhong Wu Jianguo Wu Ka-Hing Wong Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1 Food Science and Human Wellness ptr-senps (polysaccharide-protein complex functionalized selenium nanoparticles) acetaminophen-induced hepatotoxicity nuclear factor erythroid 2-related factor 2 cytochrome p450 enzyme 2e1 mitochondria |
| title | Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1 |
| title_full | Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1 |
| title_fullStr | Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1 |
| title_full_unstemmed | Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1 |
| title_short | Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1 |
| title_sort | functionalized selenium nanoparticles ameliorated acetaminophen induced hepatotoxicity through synergistically triggering pkcδ nrf2 signaling pathway and inhibiting cyp 2e1 |
| topic | ptr-senps (polysaccharide-protein complex functionalized selenium nanoparticles) acetaminophen-induced hepatotoxicity nuclear factor erythroid 2-related factor 2 cytochrome p450 enzyme 2e1 mitochondria |
| url | https://www.sciopen.com/article/10.26599/FSHW.2022.9250080 |
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