Melatonin prevents glyphosate-induced hepatic lipid accumulation in roosters via activating Nrf2 pathway.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
    • Subject Terms:
      Glycine*/analogs & derivatives ; Glycine*/pharmacology ; NF-E2-Related Factor 2*/metabolism ; Glyphosate* ; Liver*/drug effects ; Liver*/metabolism ; Liver*/pathology ; Lipid Metabolism*/drug effects ; Hepatocytes*/drug effects ; Hepatocytes*/metabolism ; Melatonin*/pharmacology ; Melatonin*/therapeutic use ; Chemical and Drug Induced Liver Injury*/drug therapy ; Chemical and Drug Induced Liver Injury*/prevention & control ; Chemical and Drug Induced Liver Injury*/metabolism ; Chemical and Drug Induced Liver Injury*/pathology ; Signal Transduction*/drug effects ; Herbicides*/toxicity; Animals ; Chickens ; Oxidative Stress/drug effects ; Male ; Cells, Cultured ; Chick Embryo ; Molecular Docking Simulation ; Antioxidants/pharmacology
    • Abstract:
      Background: Glyphosate (GLY) is a widely used herbicide with well-defined hepatotoxic effects, in which oxidative stress has been shown to be involved in the pathogenesis of hepatotoxicity. Melatonin (MET), an effective free radical scavenger, has been revealed to alleviate drug-induced liver damage by inhibiting oxidative stress.
      Methods: In this study, a rooster model with primary chicken embryo hepatocytes was applied to elucidate the therapeutic effects of MET against GLY-induced hepatic damage and the potential mechanism. Histopathological examinations, biochemical tests and immunoblotting analysis were used to monitor the protective effects of MET on GLY-induced hepatic lipid accumulation. Molecular docking analysis was used to reveal the key reason of MET-improved hepatic lipid deposition.
      Results: Data firstly showed that MET administration markedly improved GLY-induced hepatic injury, as evidenced by normalized liver enzymes and alleviated pathological changes of liver tissues. Moreover, MET supplementation alleviated GLY-induced hepatic lipid accumulation, which was correlated with improved serum and hepatic lipid profiles and normalized expression of lipolysis- and lipogenesis-related proteins. Notably, MET significantly inhibited vital enzymes involved in stimulating oxidative stress. Moreover, MET enhanced GLY-inhibited Nrf2 nuclear transcription and increased the expressions of its downstream target genes HO1 and NQO1. Further studies revealed that MET may interact with Nrf2 to enhance nuclear translocation of Nrf2.
      Conclusion: Collectively, our results provide the first direct evidence that MET is a novel regulator of Nrf2, highlighting that Nrf2 may be a potential therapeutic target for GLY-induced lipotoxic liver injury.
      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: Glyphosate; Hepatic steatosis; Lipogenesis; Lipolysis; Melatonin; Nrf2
    • Accession Number:
      TE7660XO1C (Glycine)
      0 (NF-E2-Related Factor 2)
      4632WW1X5A (Glyphosate)
      JL5DK93RCL (Melatonin)
      0 (Herbicides)
      0 (Antioxidants)
    • Publication Date:
      Date Created: 20240921 Date Completed: 20241011 Latest Revision: 20241011
    • Publication Date:
      20241011
    • Accession Number:
      10.1016/j.intimp.2024.113180
    • Accession Number:
      39305889