Selenomethionine supplementation mitigates fluoride-induced liver apoptosis and inflammatory reactions by blocking Parkin-mediated mitophagy in mice.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0330500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1026 (Electronic) Linking ISSN: 00489697 NLM ISO Abbreviation: Sci Total Environ Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam, Elsevier.
    • Subject Terms:
      Mitophagy*/drug effects ; Ubiquitin-Protein Ligases*/metabolism ; Ubiquitin-Protein Ligases*/genetics ; Apoptosis*/drug effects ; Fluorides*/toxicity ; Selenomethionine*/pharmacology ; Liver*/drug effects; Animals ; Mice ; Inflammation ; Dietary Supplements ; Oxidative Stress/drug effects
    • Abstract:
      As an environmental pollutant, fluoride-induced liver damage is directly linked to mitochondrial alteration and oxidative stress. Selenium's antioxidant capacity has been shown to alleviate liver damage. Emerging research proves that E3 ubiquitin ligase Park2 (Parkin)-mediated mitophagy may be a therapeutic target for fluorosis. The current study explored the effect of diverse selenium sources on fluoride-caused liver injury and the role of Parkin-mediated mitophagy in this intervention process. Therefore, this study established a fluoride-different selenium sources co-intervention wild-type (WT) mouse model and a fluoride-optimum selenium sources co-intervention Parkin gene knockout (Parkin-/-) mouse model. Our results show that selenomethionine (SeMet) is the optimum selenium supplementation form for mice suffering from fluorosis when compared to sodium selenite and chitosan nano‑selenium because mice from the F-SeMet group showed more closely normal growth and development levels of liver function, antioxidant capacity, and anti-inflammatory ability. Explicitly, SeMet ameliorated liver inflammation and cell apoptosis in fluoride-toxic mice, accomplished through downregulating the mRNA and protein expression levels associated with mitochondrial fusion and fission, mitophagy, apoptosis, inflammatory signalling pathway of nuclear factor-kappa B (NF-κB), reducing the protein expression levels of PARKIN, PTEN-induced putative kinase1 (PINK1), SQSTM1/p62 (P62), microtubule-associated protein light chain 3 (LC3), cysteinyl aspartate specific proteinase 3 (CASPAS3), as well as restraining the content of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ). The Parkin-/- showed comparable positive effects to the SeMet in the liver of fluorosis mice. The structure of the mitochondria, mRNA, protein expression levels, and the content of proinflammatory factors in mice from the F Parkin-/- and F + SeMet Parkin-/- groups closely resembled those in the F + SeMet WT group. Overall, the above results indicated that SeMet could alleviate fluoride-triggered inflammation and apoptosis in mice liver via blocking Parkin-mediated mitophagy.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Fluorosis; Liver; Mitophagy; Parkin; Selenomethionine
    • Accession Number:
      EC 2.3.2.27 (Ubiquitin-Protein Ligases)
      EC 2.3.2.27 (parkin protein)
      Q80VPU408O (Fluorides)
      964MRK2PEL (Selenomethionine)
    • Publication Date:
      Date Created: 20240814 Date Completed: 20240912 Latest Revision: 20241104
    • Publication Date:
      20241104
    • Accession Number:
      10.1016/j.scitotenv.2024.175458
    • Accession Number:
      39142410