Nootkatone confers hepatoprotective and anti-fibrotic actions in a murine model of liver fibrosis by suppressing oxidative stress, inflammation, and apoptosis

Amani Kurdi, Kamal Hassan, Balaji Venkataraman, Mohanraj Rajesh

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

In this study, the hepatoprotective and anti-fibrotic actions of nootkatone (NTK) were investigated using carbon tetrachloride (CCl4)-induced liver fibrosis in mice. CCl4 administration elevated serum aspartate and alanine transaminases levels, respectively. In addition, CCl4 produced hepatic oxidative and nitrative stress, characterized by diminished hemeoxygenase-1 expression, antioxidant defenses, and accumulation of 4-hydroxynonenal and 3-nitrotyrosine. Furthermore, CCl4 administration evoked profound expression of pro-inflammatory cytokine expressions such as tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-1β in hepatic tissues, which corroborated with nuclear factor κB activation. Additionally, CCl4-treated animals exhibited higher apoptosis, characterized by increased caspase 3 activity, DNA fragmentation, and poly (ADP-ribose) polymerase activation. Moreover, histological and biochemical investigations revealed marked fibrosis in the livers of CCl4-administered animals. However, NTK treatment mitigated CCl4-induced phenotypic changes. In conclusion, our findings suggest that NTK exerts hepatoprotective and anti-fibrotic actions by suppressing oxidative stress, inflammation, and apoptosis.

Original languageEnglish
Article numbere22017
JournalJournal of Biochemical and Molecular Toxicology
Volume32
Issue number2
DOIs
Publication statusPublished - Feb 2018

Keywords

  • apoptosis
  • inflammation
  • liver fibrosis
  • nootkatone
  • oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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