Oxymatrine Induces Liver Injury through JNK Signalling Pathway Mediated by TNF-α In Vivo.
Oxymatrine (OMT) is a traditional Chinese medicine monomer and has been used for the treatment of chronic viral hepatitis and many other diseases. We aimed to investigate whether OMT could induce hepatotoxicity in mice and explored the preliminary mechanisms of toxic effects. Twenty-four Institute for Cancer Research male mice were randomly divided into four groups: control group, 40, 160 and 320 mg/kg OMT-treated group. OMT was orally administered once daily for 7 days. The OMT-treated group exhibited an improved liver index and increase in serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase,augmented liver histological injury, elevated levels of malondialdehyde and tumour necrosis factor alpha (TNF-α) accompanied by the activation of caspase-9/-8/-3, up-regulated expressions of tumour necrosis factor receptor l (TNFR1), TNF receptor-associated structure domain (TRADD) and phosphorylation of stress-activated protein kinase/c-jun N-terminal protein kinases (p-SAPK/JNK). Altogether, these results suggest that OMT at a dose of 320 mg/kg leads to liver damage and is related to the activation of JNK signalling pathway mediated by TNF-α in the liver of mice.
College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China.
Hong
H
Lu
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, China.
Li
L
Zhang
College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China.
Li-Li
LL
Gu
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, China.
Bi-Yu
BY
Hou
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, China. dugh@imm.ac.cn.
Guan-Hua
GH
Du
D000470:Alkaloids / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011807:Quinolizines / Q000008:administration & dosage / Q000009:adverse effects*; D011897:Random Allocation; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D053199:TNF Receptor-Associated Death Domain Protein / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000093842:Matrines
D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D000998:Antiviral Agents; D048031:JNK Mitogen-Activated Protein Kinases; D011807:Quinolizines; D047888:Receptors, Tumor Necrosis Factor, Type I; D053199:TNF Receptor-Associated Death Domain Protein; D014409:Tumor Necrosis Factor-alpha; C481226:Tradd protein, mouse; C037573:oxymatrine; D000093842:Matrines