OBJECTIVETo investigate the intervention effect of aqueous fractions from Boschniakia rossica (BRAF) on hepatic oxidative stress in mice with liver injury induced by carbon tetrachloride (CCl4).

METHODThe experimental mice were randomly assigned into the normal control group, the model group, the silymarin (positive control) group, as well as high and low dose BRAF groups. Mice were treated intragastrically with silymarin or BRAF once every day for 7 days. At the end of the experiment, CCl4 was injected intraperitoneally into the mice to establish the acute liver injury model. The pathological changes was detected with hematoxylin and eosin (HE) staining, and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), superoxide dismutase (SOD) , catalase (CAT), glutathione peroxidase (GPx), Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, and the contents of reduced glutathione (GSH) and malondialdehyde (MDA) were detected by the colorimetric method.

RESULTBRAF significantly reduced ALT, AST and ALP activities in serum, alleviated hepatic injury induced by CCl4, increased SOD, CAT, GPx and GSH levels in liver, and SOD, Na + -K + -ATPase and Ca2+ -Mg2 + -ATPase activities in liver mitochondria, and decreased the MDA content in liver and liver mitochondria.

CONCLUSIONBRAF reduces hepatic oxidative stress in mice with acute liver injury induced by CCl4, thereby showing the protective effect on mice with acute liver injury induced by CCl4.

Animals ; Carbon Tetrachloride ; toxicity ; Chemical and Drug Induced Liver Injury ; enzymology ; metabolism ; pathology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Liver ; drug effects ; enzymology ; metabolism ; pathology ; Male ; Mice ; Mitochondria ; drug effects ; metabolism ; Orobanchaceae ; chemistry ; Oxidative Stress ; drug effects ; Solubility ; Water ; chemistry

OBJECTIVETo observe the effects of different therapeutic methods and the recipes of Chinese medicine (CM) on the activation of c-Jun N-terminal kinase (JNK) in Kupffer cells of rats with fatty liver disease and to explore the mechanisms of these therapeutic methods.

METHODSBy using a random number table, 98 rats were randomly divided into 7 groups: control group, model group, and 5 treatment groups, including soothing Liver (Gan) recipe group, invigorating Spleen (Pi) recipe group, dispelling dampness recipe group, promoting blood recipe group, and complex recipe group. Rats in the control group were fed with normal food and distilled water by gastric perfusion, while rats in the model group were fed with high-fat food and distilled spirits by gastric perfusion. Rats in the 5 treatment groups were fed with high-fat food and corresponding recipes by gastric perfusion. Twelve weeks later, all rats were sacrificed and liver tissues were stained for pathohistological observation. Kupffer cells were isolated from livers of rats to evaluate JNK and phospho-JNK expressions by Western blotting.

RESULTSThe grade of hepatic steatosis was higher in the model group than the control group (P<0.05). Compared with the model group, the grade of fatty degeneration in soothing Liver recipe group and invigorating Spleen recipe group were significantly ameliorated (P<0.05). Expressions of JNK and phospho-JNK in Kupffer cells were significantly higher in the model group than those in the control group (P<0.05, P<0.01). Compared with the model group, expressions of JNK in all treatment groups decreased, especially in invigorating Spleen recipe group and promoting blood recipe group (P<0.05). Compared with the model group, expressions of phospho-JNK in all treatment groups declined significantly (P<0.01), especially in soothing Live recipe group and invigorating Spleen recipe group.

CONCLUSIONSThe high expressions of JNK and phospho-JNK in Kupffer cells might play an important role in the pathogenesis of fatty liver disease in rats. The recipes of CM, especially invigorating Spleen recipe and soothing Liver recipe, might protect liver against injury by reducing the total JNK protein content and inhibiting the activation of JNK protein in Kupffer cells of fatty liver model rats, which showed beneficial effects on fatty liver disease.

Animals ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Enzyme Activation ; drug effects ; Fatty Liver ; enzymology ; pathology ; therapy ; Hepatocytes ; drug effects ; enzymology ; pathology ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Kupffer Cells ; drug effects ; enzymology ; pathology ; Liver ; drug effects ; enzymology ; pathology ; Phosphorylation ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the mechanism of salvianolic acid B (Sal B) action against liver fibrosis through preventing lipid peroxidation and regulating MMP-2 activity in liver.

METHODThe liver fibrotic model was induced through intraperitoneally injection of DMN at a dose of 10 microg x kg(-1) for every other day and lasting for 4 weeks. Sal B was administered (10 mg x kg(-1)), and perindopril (5 mg x kg(-1)) was used as positive control. Hepatic inflammation and collagen were observed with HE and sirius red staining. The liver function including serum ALT, AST activity, Alb and total bilirubin (T. Bil) level were determined. The hepatic lipid peroxidation including SOD and GST activities and GSH content were measured. Hepatic hydroxyproline (Hyp) content was detected with Jamall's method. The activity of metalloproteinase was assayed by gelatin zymography. The expressions of alpha-SMA, Col I in liver tissue were analyzed by Western blot.

RESULTThe model rats had higher serum T. Bil content, ALT and AST activities but lower Alb content than the normal rats, also had remarkable inflammatory necrosis and collagen deposition in liver, with much higher Hyp content, protein expression of alpha-SMA and collagen I and MMP-2 activity in liver, but had a decreased GSH content, SOD and GST activities. Both Sal B and perindopril attenuated hepatic injury and collagen deposition in model rats, decreased serum ALT activity and hepatic Hyp content, down-regulated alpha-SMA and collagen I protein expressions and metalloproteinase-2 activity than those in the model group, but increased SOD activity and GSH content, and Sal B decreased serum T. Bil content and increased GST activity. Sal B had a much better comprehensive actions than perindopril.

CONCLUSIONSal B has a good preventive action against liver fibrosis, the action mechanism is related to the prevention from lipid peroxidation and down-regulation of metalloproteinase-2 activity in fibrotic liver.

Animals ; Benzofurans ; therapeutic use ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; enzymology ; metabolism ; pathology ; Liver Cirrhosis ; drug therapy ; enzymology ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Rats ; Rats, Sprague-Dawley

Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; enzymology ; pathology ; virology ; Hepacivirus ; genetics ; Humans ; Liver Neoplasms ; enzymology ; pathology ; virology ; Telomerase ; metabolism ; Viral Core Proteins ; genetics ; metabolism

OBJECTIVETo study on the time-toxicity and dose-toxicity relationships caused by multiple dose water extraction components of Evodia Fructus to mice.

METHODMice were grouped according to different time or dose points, to observe the death condition and toxicity of mice. The changes of the activity of ALT, AST and liver, kidney index were detected, and the morphological changes of liver tissue were observed under light microscope.

RESULTOn the first day after administration the hepatotoxicity which displayed with obvious increase of ALT, AST activity in serum and liver tissue and hepatic injury appeared. On the third day the hepatotoxicity kept a higher level that the active units in serum ALT, AST were significantly higher than the normal group. On the 7th day after administration ALT, AST level in serum are restored near normality. Compared with the normal group, within 7 days after the administration, water extracted components in 0.63-5.0 g x kg(-1) dose scope could cause significant damage to liver, the activity of ALT, AST, AKP, TBI elevated, while ALB reduced, and liver ratio increased, and under light microscope, the different doses' liver tissue of mice all had different degree's edema, fatty degeneration in liver cells and interstitial congestion. There were certain time-toxicity and dose-toxicity relationships. The above-mentioned change gradually aggravated with dose increasing, and it was the obvious discrepancy compared with distilled water control group.

CONCLUSIONMultiple intragastric administrations of water extracted components of Evodia Fructus with certain dosage may induce acute hepatotoxical injury in mice and show certain "dosage-time-toxicity" relationship.

Alanine Transaminase ; blood ; metabolism ; Animals ; Aspartate Aminotransferases ; blood ; metabolism ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; metabolism ; toxicity ; Evodia ; chemistry ; Female ; Fruit ; chemistry ; Kidney ; drug effects ; enzymology ; metabolism ; Liver ; drug effects ; enzymology ; metabolism ; pathology ; Male ; Mice

Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is easily introduced to humans via consumption of grilled or smoked meat. BaP causes harmful oxidative effects on cell development, growth and survival through an increase in membrane lipid peroxidation, oxidative DNA damage and mutagenesis. Therefore, the present study was conducted to evaluate the synergistic effects of BaP on oxidative stress in hepatic tumors. In this study, we established a hepatic tumor model by injecting rat hepatoma N1-S1 cells into healthy rats. Changes in the abundance of heat shock proteins (HSPs), antioxidant enzymes and pro-inflammatory cytokines were then investigated by western blot analysis. In addition, we examined changes in oxidative stress levels. Injection of N1-S1 cells or concomitant injection of BaP and N1-S1 cells resulted in the formation of hepatic tumors at the injection site. Evaluation of rat plasma reveals that hepatic tumors induced by BaP and N1-S1 cells expresses higher levels of Hsp27, superoxide dismutase (SOD), and tumor necrosis factor-alpha (TNF-alpha) when compared to those induced by N1-S1 cells only. The collective results of this study suggest that BaP exerts synergistic effects on the expression of HSP, cytokines and antioxidant enzymes in hepatic tumors induced by rat hepatoma N1-S1 cells.
Animals ; Antioxidants/*metabolism ; Benzo(a)pyrene/*pharmacology ; Carcinoma, Hepatocellular/metabolism/pathology ; Cell Line, Tumor/*drug effects ; Cytokines/*metabolism ; Heat-Shock Proteins/*metabolism ; Humans ; Liver Neoplasms/*enzymology/*metabolism/pathology ; Male ; Neoplasms, Experimental/metabolism/pathology ; Oxidative Stress/drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the protective effect of atractylenolide I on immunological liver injury induced by BCG and LPS.

METHODKunming mice were randomly divided into 6 groups: the normal group, the model group, positive control biphenyl group, the atractylenolide I high does group, the atractylenolide I middle dose group and the atractylenolide I low dose group (60, 120, 240 mg x kg(-1)), with 12 mice in each group. Immunological liver injury in mice was induced by BCG and LPS to compared liver index and spleen index and detect content of serum ALT, AST, MDA and GSH-px in serum and NO, iNOS, TNF-alpha in serum and liver homogenate. Liver pathological changes were observed by HE staining.

RESULTBoth of atractylenolide I and biphenyl remarkably decrease the increased live index and spleen index (P < 0.05), improve the histopathological changes in liver and pathological grades of liver tissues and relieve the inflammatory reaction induced by BCG and LPS. They showed a notable effect in improving MDA and GSH-px in serum.

CONCLUSIONAtractylenolide I can obviously protect immunological injury liver a dose-dependent manner within the range of test doses. Its mechanism may be related to release or over expression of inhibitory inflammatory medium such as NO, iNOS and TNF-alpha.

Animals ; Chemical and Drug Induced Liver Injury ; immunology ; metabolism ; pathology ; prevention & control ; Lactones ; pharmacology ; Lipopolysaccharides ; adverse effects ; Liver ; drug effects ; enzymology ; metabolism ; pathology ; Male ; Mice ; Mycobacterium bovis ; immunology ; Oxidative Stress ; drug effects ; immunology ; Sesquiterpenes ; pharmacology

Betulinic acid (BA), a pentacyclic lupane-type triterpene, has a wide range of bioactivities. The main objective of this work was to evaluate the hepatoprotective activity of BA and the potential mechanism underlying the ability of this compound to prevent liver damage induced by alcohol in vivo. Mice were given oral doses of BA (0.25, 0.5, and 1.0 mg/kg) daily for 14 days, and induced liver injury by feeding 50% alcohol orally at the dosage of 10 ml/kg after 1 h last administration of BA. BA pretreatment significantly reduced the serum levels of alanine transaminase, aspartate transaminase, total cholesterol, and triacylglycerides in a dose-dependent manner in the mice administered alcohol. Hepatic levels of glutathione, superoxide dismutase, glutathione peroxidase, and catalase were remarkably increased, while malondialdehyde contents and microvesicular steatosis in the liver were decreased by BA in a dose-dependent manner after alcohol-induced liver injury. These findings suggest that the mechanism underlying the hepatoprotective effects of BA might be due to increased antioxidant capacity, mainly through improvement of the tissue redox system, maintenance of the antioxidant system, and decreased lipid peroxidation in the liver.
Animals ; Antioxidants/pharmacology ; Blood Chemical Analysis ; Enzymes/blood ; Ethanol/*toxicity ; Lipid Peroxidation/drug effects ; Liver/*drug effects/enzymology/metabolism/pathology ; Male ; Mice ; Random Allocation ; Triterpenes/*pharmacology

OBJECTIVETo study the role of CYP2E1 in the protective effects and mechanism of garlic oil (GO) on the peripheral nerve injuries induced by n-hexane.

METHODSFifty male Wistar rats were randomly divided into five groups (n = 10): the control, the GO (80 mg/kg) control, the n-hexane (2000 mg/kg) model, the low dose GO (40 mg/kg) plus n-hexane, and the high dose GO (80 mg/kg) plus n-hexane groups. All rats were treated by intragastric administration 6 times a week for 10 weeks. The gait scores were determined every two weeks for monitoring the peripheral neurotrosis. All rats were sacrificed in 10 weeks, the activities and expression levels of hepatic CYP2E1 and 2, 5-HD in serum were examined.

RESULTSAs compared with control group, the content and activity of hepatic CYP2E1 in GO control group reduced by 83.1% and 48.3% respectively (P < 0.01), the content and activity of hepatic CYP2E1 in model group increased by 112.5% and 72.2% respectively (P < 0.01). As compared with model group, the contents of hepatic CYP2E1 in low dose and high dose GO groups reduced by 32.9% and 39.1% respectively, the activities of hepatic CYP2E1 in low dose and high dose GO groups reduced by 27.4% and 44.5% respectively (P < 0.01); the contents of serum 2,5-HD in low dose and high dose GO groups reduced by 47.7% and 78.7% respectively (P < 0.01). The gait scores in model, low dose and high dose GO groups were significantly lower than that in control group, but the gait scores in low dose and high dose GO groups were significantly lower than that in model group (P < 0.05).

CONCLUSIONGarlic oil can effectively reduce the peripheral neurotrosis induced by n-hexane due to the decreased content and activity of hepatic CYP2E1, resulting in the reduced formation of 2, 5-HD from n-hexane.

Animals ; Cytochrome P-450 CYP2E1 ; metabolism ; Garlic ; Hexanes ; toxicity ; Liver ; drug effects ; enzymology ; Male ; Peripheral Nerves ; drug effects ; pathology ; Plant Oils ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effect of lidamycin (LDM) on telomerase activity in human hepatoma BEL-7402 cells under the condition of LDM inducing mitotic cell death and senescence.

METHODSChromatin condensation was detected by co-staining with Hoechst 33342 and PI. Cell multinucleation was observed by Giemsa staining and genomic DNA was separated by agarose gel electrophoresis. Fluorescent intensity of Rho123 was determined for mitochondrial membrane potential. MTT assay and SA-beta-gal staining were employed to analyze the senescence-like phenotype. The expression of proteins was analyzed by Western blot. Telomerase activity was assayed by telomerase PCR-ELISA.

RESULTSMitotic cell death occurred in LDM-treated cells characterized by unique and atypical chromatin condensation, multinucleation and increased mitochondrial membrane potential. However, no apoptotic bodies or DNA ladders were found. In addition, apoptosis-related proteins remained nearly unaltered. Senescence-like phenotype was identified by increased and elongated size of cells, growth retardation, enhanced SA-beta-gal activity and the changes of senescence-related protein expression. Telomerase activity markedly decreased (P<0.01) in LDM-treated hepatoma BEL-7402 cells.

CONCLUSIONMitotic cell death and senescence could be triggered simultaneously or sequentially after exposure of hepatoma BEL-7402 cells to LDM. The decrease in telomerase activity may play a key role in the defective mitosis and aging morphology. Further investigation of detailed mechanism is needed.

Aminoglycosides ; pharmacology ; Antibiotics, Antineoplastic ; pharmacology ; Apoptosis ; drug effects ; Azure Stains ; Benzimidazoles ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Cell Nucleus ; drug effects ; metabolism ; Cellular Senescence ; drug effects ; Chromatin ; metabolism ; DNA, Neoplasm ; analysis ; Dose-Response Relationship, Drug ; Enediynes ; pharmacology ; Genome, Human ; genetics ; Humans ; Liver Neoplasms ; enzymology ; pathology ; Membrane Potential, Mitochondrial ; drug effects ; Mitosis ; drug effects ; Phenotype ; Propidium ; Telomerase ; metabolism ; Time Factors ; beta-Galactosidase ; metabolism