Journal
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
Volume 32, Issue 2, Pages -Publisher
WILEY
DOI: 10.1002/jbt.22017
Keywords
apoptosis; inflammation; liver fibrosis; nootkatone; oxidative stress
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Funding
- College of Medicine and Health Sciences, United Arab Emirates University [NP-14-40, 31M205]
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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-, monocyte chemoattractant protein-1, and interleukin-1 in hepatic tissues, which corroborated with nuclear factor B 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.
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