Ferulic acid attenuated acetaminophen-induced hepatotoxicity though down-regulating the cytochrome P 2E1 and inhibiting toll-like receptor 4 signaling-mediated inflammation in mice.
Ferulic acid (FA), a phenolic acid which is abundant in vegetables and fruits, has been reported to exert anti-oxidative and anti-inflammatory activities. In the present study, the pharmacological effects and the underlying mechanisms of FA in mice with acetaminophen-induced hepatotoxicity were investigated. Our results revealed that FA pretreatment inhibited the augments of serum aminotransferases in a dose-dependent manner and attenuated the hepatic histopathological abnormalities and hepatocellular apoptosis in acetaminophen (APAP) exposed mice. Moreover, FA inhibited the expression of cytochrome P450 2E1 (CYP2E1), enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) as well as the contents of glutathione (GSH). Furthermore, FA markedly attenuated acetaminophen-induced serum tumor necrosis factor (TNF)-α and interleukin (IL)-1β production, suppressed Toll-like receptor (TLR) 4 expression and dampened p38 mitogen-activated (MAPK) and nuclear factor kappa (NF-κB) activation. These data suggested that FA could effectively protect against APAP-induced liver injury by down-regulated expression of CYP 2E1 and the suppression of TLR4-mediated inflammatory responses.
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University Chongqing 400016, China.
Junhui
J
Yuan
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University Chongqing 400016, China.
Kuang
K
Ge
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University Chongqing 400016, China.
Junhuan
J
Mu
Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University Chongqing 400016, China.
Jiang
J
Rong
Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University Chongqing 400016, China.
Li
L
Zhang
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University Chongqing 400016, China.
Bin
B
Wang
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University Chongqing 400016, China.
Jingyuan
J
Wan
Department of Anatomy, Chongqing Medical University Chongqing 400016, China.
Gong
G
Xia
Ferulic acid; acetaminophen; cytochrome P450 2E1; hepatotoxicity; toll-like receptor (TLR) 4