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Nootkatone confers hepatoprotective and anti‐fibrotic actions in a murine model of liver fibrosis by suppressing oxidative stress, inflammation, and apoptosis
Author(s) -
Kurdi Amani,
Hassan Kamal,
Venkataraman Balaji,
Rajesh Mohanraj
Publication year - 2018
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22017
Subject(s) - oxidative stress , ccl4 , chemistry , carbon tetrachloride , nitrotyrosine , inflammation , apoptosis , liver injury , fibrosis , pharmacology , tumor necrosis factor alpha , endocrinology , biochemistry , immunology , medicine , nitric oxide synthase , enzyme , organic chemistry
In this study, the hepatoprotective and anti‐fibrotic actions of nootkatone (NTK) were investigated using carbon tetrachloride (CCl 4 )‐induced liver fibrosis in mice. CCl 4 administration elevated serum aspartate and alanine transaminases levels, respectively. In addition, CCl 4 produced hepatic oxidative and nitrative stress, characterized by diminished hemeoxygenase‐1 expression, antioxidant defenses, and accumulation of 4‐hydroxynonenal and 3‐nitrotyrosine. Furthermore, CCl 4 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, CCl 4 ‐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 CCl 4 ‐administered animals. However, NTK treatment mitigated CCl 4 ‐induced phenotypic changes. In conclusion, our findings suggest that NTK exerts hepatoprotective and anti‐fibrotic actions by suppressing oxidative stress, inflammation, and apoptosis.