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Oeanolic acid protects against the hepatotoxicity of D-galactosame plus endotoxin in mice
- Source :
- Biomedicine & Pharmacotherapy. 93:1040-1046
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Oleanolic acid (OA) is a triterpenoid contained in many herbal medicines. The aim of this study was to investigate the protective effect of OA against D-galactosame plus lipopolysaccharides (D-GalN/LPS)-induced acute liver injury and the underling mechanisms. Mice were randomly divided into normal control with vehicles only (corn oil), D-GalN/LPS only (700mg/10μg/kg, ip), OA-po (200μmol/kg in corn oil, po) plus D-GalN/LPS, and OA-sc (50μmol/kg in 2% tween 80, sc) plus D-GalN/LPS groups. OA pretreatment was conducted twice daily for 4 consecutive days. Hepatotoxicity was evaluated by histopathology, serum enzyme activity, hepatic lipid peroxidation and GSH levels. To reveal the possible mechanisms of the protection, mRNA and protein expressions of toxicity-relevant genes and proteins were examined by real-time RT-PCR and western-blot analysis. Both OA-po and OA-sc at therapeutic doses successfully protected liver injury induced by D-GalN/LPS, as evidenced by reduced serum enzyme activities, prevented liver hemorrhage, massive necrosis, and reduced degenerative lesions. OA increased hepatic GSH contents and decreased lipid peroxidation (MDA) levels. Furthermore, OA significantly inhibited the mRNA expression of the tumor necrosis factor-α (TNF-α) and ER responsive gene Gadd45. D-GalN/LPS-induced activation of p-JNK and NF-κB p65, and protein overexpression of caspase-3, caspase-8, and COX2 were significantly suppressed by OA. These results clearly demonstrated OA-po is effective as OA-sc in protecting against D-GalN/LPS-induced liver injury, and the protection mechanisms are related to reduction of oxidative damage, suppression of TNFα-triggered signaling through the NF-kB and JNK pathways, thus reducing apoptosis and hepatocellular death.
- Subjects :
- Lipopolysaccharides
Male
0301 basic medicine
Galactosamine
Pharmacology
Protective Agents
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Animals
Oleanolic Acid
Oleanolic acid
Liver injury
Tumor Necrosis Factor-alpha
NF-kappa B
General Medicine
Glutathione
medicine.disease
NFKB1
Endotoxins
030104 developmental biology
chemistry
Apoptosis
030220 oncology & carcinogenesis
Immunology
Tumor necrosis factor alpha
Chemical and Drug Induced Liver Injury
Corn oil
Subjects
Details
- ISSN :
- 07533322
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Biomedicine & Pharmacotherapy
- Accession number :
- edsair.doi.dedup.....3d523beccffe3522c8c3b3b7725a4326