The aim of the present study was to investigate the effects of dexmedetomidine (DEX) on acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-Gal) and the underlying mechanism. Male BALB/c mice were intraperitoneally injected with LPS/D-Gal to induce acute liver injury model, and pretreated with DEX or in combination with the autophagy inhibitor, 3-methyladenine (3-MA) 30 min before injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as myeloperoxidase (MPO) activity in liver tissue were determined with the corresponding kits. Serum tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels were determined by ELISA. The protein expression levels of LC3-II and P62 in liver tissue were determined by Western blot. Liver histopathological changes were detected by HE staining. The results showed that, compared with control group, LPS/D-Gal enhanced ALT and AST activity, increased TNF-α and IL-6 levels, as well as MPO activity, up-regulated LC3-II and P62 protein expression levels, and significantly induced pathological damage in liver tissue. DEX reversed the above changes in the LPS/D-Gal group, whereas these protective effects of DEX were blocked by 3-MA. The above results suggest that DEX alleviates LPS/D-Gal-induced acute liver injury, which may be associated with the up-regulation of LC3-II protein expression and the activation of autophagy.
Alanine Transaminase ; Animals ; Chemical and Drug Induced Liver Injury/drug therapy* ; Dexmedetomidine/pharmacology* ; Galactosamine/toxicity* ; Interleukin-6/blood* ; Lipopolysaccharides/toxicity* ; Liver ; Male ; Mice ; Mice, Inbred BALB C ; Microtubule-Associated Proteins/metabolism* ; Tumor Necrosis Factor-alpha/blood* ; Up-Regulation

OBJECTIVETo investigate the protective effect of soyasaponins on acute liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in mice.

METHODThe mice were randomly divided into five groups: the normal control, the model group, the silymarin (positive control) group, and soyasaponins high and low-dose groups. They were administered with drugs once every day for 7 days. At the end of the experiment, GalN and LPS were injected intraperitoneally to all of the groups except for the normal group to establish the acute liver injury model. The pathological changes were detected with hematoxylin & eosin (HE) staining, tumor necrosis factor-alpha (TNF-alpha) was detected by ELISA method, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), and the activation of Caspase-3 and Caspase-8 were detected by the colorimetric method.

RESULTSoyasaponins could reduce the activities of serum ALT and AST, the acute hepatic injury induced by GalN/LPS, serum TNF-alpha level, hepatic NO and MDA contents, and the Caspase-3 and Caspase-8 activations of liver tissues, and increase the hepatic CAT, GPx, GST and GSH levels.

CONCLUSIONSoyasaponins shows the protective effect on acute liver injury induced by GalN and LPS in mice, which may be related to its antioxidative ability and anti-liver apoptosis.

Alanine Transaminase ; blood ; Animals ; Antioxidants ; metabolism ; Apoptosis ; drug effects ; Aspartate Aminotransferases ; blood ; Caspases ; metabolism ; Chemical and Drug Induced Liver Injury ; metabolism ; pathology ; prevention & control ; Galactosamine ; toxicity ; Lipopolysaccharides ; toxicity ; Liver ; pathology ; Male ; Mice ; Saponins ; pharmacology ; Soybeans ; chemistry

OBJECTIVETo investigate the protective effects and mechanism of triterpenoids on primarily cultured rat hepatocytes injured by D-galactosamine (D-GalN) or carbon tetrachloride (CCl4).

METHODSRat hepatocytes were isolated by two-step collagenase perfusion and cultured in RPMI 1640 medium. Protective effects of asiatic acid (AA) and beta-glycyrrhetinic acid (GA) were evaluated on hepatocytes injured by D-GalN (2 mmol/L) or CCl4 (10 mmol/L). Cell morphology was observed by light microscope, cell viability was measured by MTT assay, AST and LDH were determined by an automatic analyzer. Fluorescence assay was applied to test reactive oxygen species (ROS), nitric oxide end products (NOx) and reduced glutathione (GSH), and JC-1 staining was used to determine mitochondria membrane potential (DeltaPsim).

RESULTSAST and LDH in medium were decreased when treated with AA and GA after D-GalN injury (P<0.05), furthermore AA enhanced the hepatocyte viability (P<0.05). Moreover, AA and GA significantly reduced ROS and NOx generation, and ameliorated DeltaPsim lost induced by D-GalN. AA also inhibited GSH decrease due to D-GalN and CCl4 treatment.

CONCLUSIONBoth AA and GA could protect hepatocytes from D-GalN and CCl4 injuries, which is associated with reducing intracellular ROS and NOx, reversing GSH depression and ameliorating DeltaPsim lost.

Animals ; Carbon Tetrachloride ; toxicity ; Cell Survival ; drug effects ; Cells, Cultured ; Galactosamine ; toxicity ; Glycyrrhetinic Acid ; pharmacology ; Hepatocytes ; cytology ; drug effects ; metabolism ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Nitric Oxide ; metabolism ; Pentacyclic Triterpenes ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Triterpenes ; pharmacology