TY - JOUR
T1 - Nootkatone confers hepatoprotective and anti-fibrotic actions in a murine model of liver fibrosis by suppressing oxidative stress, inflammation, and apoptosis
AU - Kurdi, Amani
AU - Hassan, Kamal
AU - Venkataraman, Balaji
AU - Rajesh, Mohanraj
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2018/2
Y1 - 2018/2
N2 - 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.
AB - 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.
KW - apoptosis
KW - inflammation
KW - liver fibrosis
KW - nootkatone
KW - oxidative stress
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U2 - 10.1002/jbt.22017
DO - 10.1002/jbt.22017
M3 - Article
C2 - 29214688
AN - SCOPUS:85041538574
SN - 1095-6670
VL - 32
JO - Journal of Biochemical and Molecular Toxicology
JF - Journal of Biochemical and Molecular Toxicology
IS - 2
M1 - e22017
ER -