ABSTRACT
OBJECTIVES: Aimed to investigate the effect and mechanism of methyl 3,4-dihydroxybenzoate (MDHB) on d-galactosamine/lipopolysaccharide (d-galN/LPS)-induced acute liver failure (ALF). METHODS: Confirmed the hepatoprotective effect and hepatotoxicity of MDHB by histopathological examination (HE) and examination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST); the expression of serum tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) was detected by ELISA; transcription levels of TNF-α, IL-1ß, IL-6 and Toll-like receptor 4 (TLR4) were detected by qRT-PCR; and phosphorylation levels of p38 and p65 were analysed by Western blot. RESULTS: Histopathological examination and examination of ALT and AST confirmed that MDHB is a low toxicity drug that can resist d-galN/LPS-induced ALF; MDHB can effectively reduce high transcription and expression of TNF-α, IL-1ß, IL-6 and TLR4 in d-galN/LPS-induced ALF; and Western blot showed that MDHB could down-regulate the expression of bax, up-regulate the expression of bcl-xl and bcl-2, and inhibit the phosphorylation of p38 and p65. CONCLUSIONS: Methyl 3,4-dihydroxybenzoate can effectively resist d-galN/LPS-induced acute liver failure, which is related to the inhibition of inflammation and apoptosis.
Subject(s)
Apoptosis/drug effects , Chemical and Drug Induced Liver Injury/drug therapy , Hydroxybenzoates/pharmacology , Inflammation/drug therapy , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Galactosamine/pharmacology , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Liver/metabolism , Liver/pathology , Male , Mice , NF-kappa B p50 Subunit/metabolism , RNA, Messenger/metabolism , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolism , bcl-Associated Death Protein/metabolism , bcl-X Protein/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
OBJECTIVE: To investigate the protective effects of Ginkgo biloba extract(GBE) on paracetamol(APAP)-induced acute hepatic injury in mice and its mechanism. METHODS: Thirty mice were randomly divided into control group, model group, GBE low, medium and high-dose(50,100,and 200 mg·kg-1)groups,with 6 mice in each group. All mice except control group were administered with APAP(300 mg/kg)for one time by intraperitoneal injection. The mice in GBE low, medium and high-dose groups were intragastric administered with GBE for 2 d consecutively, then samples were harvested for analysis. The appearance and pathology of liver were observed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and the levels of superoxide dismutase (SOD), myeloperoxidase(MPO), glutathione (GSH) and malondialdehyde (MDA) in hepatic tissue were measured. Western blot was used to detect the protein expressions of Nrf2 and HO-1. RESULTS: Compared with control group, in model group, the appearance and pathology of liver were bad, the levels of ALT,AST,TNF-α and IL-6 in serum were increased significantly(P<0.01),the levels of GSH and SOD were decreased while the levels of MDA and MPO were increased in hepatic tissue(P<0.01), the expressions of Nrf2 and HO-1 were increased in hepatic tissue(P<0.05). Compared with model group, in GBE groups, the appearance and pathology of liver were improved, the levels of ALT,AST,TNF-α and IL-6 in serum were decreased significantly(P<0.01), the levels of GSH and SOD were increased while the levels of MDA and MPO were decreased in hepatic tissue(P<0.01), the expression of Nrf2 and HO-1 were increased in hepatic tissue(P<0.05). The high-dose of GBE possessed the most obvious treatment effect among them. CONCLUSIONS: GBE may play a protective role in APAP-induced acute hepatic injury through Nrf2/HO-1 pathway.
Subject(s)
Chemical and Drug Induced Liver Injury , Acetaminophen , Alanine Transaminase , Animals , Aspartate Aminotransferases , Ginkgo biloba , Liver , Malondialdehyde , Mice , Oxidative Stress , Plant ExtractsABSTRACT
Dihydroquercetin (DHQ) is a flavonoid in the Chinese traditional herbal medicine Ramulus Euonymi, which has anti-inflammatory, antioxidant and anticancer bioactivity. In the present study, we investigated the protective effects of DHQ on acetaminophen (APAP)-induced liver injury in a mouse model for the first time. The mice received an intraperitoneal dose of APAP for model establishment. After 1 h, they were treated with DHQ at various concentrations. After 48 h of treatment, the mice were sacrificed to determine serum ALT and AST levels and the liver index, examine histopathological changes in the liver through H&E and TUNEL staining, and evaluate TNF-α and IL-6 levels using an ELISA. We also evaluated TNF-α, IL-6, Nrf2 and SOD2 mRNA expression by RT-PCR and Bcl-2, Bax and Pro-caspase-3 expression by Western blot. DHQ treatment significantly attenuated serum ALT and AST levels as well as rescued hepatomegaly. It also down-regulated TNF-α and IL-6, increased Nrf2 and SOD2 mRNA expression, down-regulated Bax, overexpressed Bcl-2 and Pro-caspase-3. Our datas suggest that DHQ treatment can effectively attenuate APAP-induced liver injury by down-regulating inflammatory factors, improving antioxidant capacity and inhibiting hepatocyte apoptosis. DHQ could be a beneficial hepatoprotective agent for the prevention and amelioration of APAP-induced acute liver injury.
