BACKGROUNDAs one of the intercellular adhesion molecules, CD58 plays important roles in promotion of the adhesion between T cells and target cells, hyperplasia, activation of T cells and natural killer cells, and balance between Th1 and Th2. We studied the relationship between the levels of CD58 expression in peripheral blood mononuclear cells (PBMCs) and severity of HBV infection.

METHODSThe levels of CD58 mRNA in PBMCs were detected using quantitative reverse transcription PCR. The percentage of CD58 positive cells was detected by flow cytometry in patients and healthy controls.

RESULTSThe levels of CD58 mRNA and the percentage of CD58 positive cells in patients infected with HBV were significantly higher than that in the control. Based on severity of HBV infection, the patients were classified into four groups. The expression of CD58 increased significantly in an order from mild chronic, moderate chronic, severe chronic to severe hepatitis groups. The levels of CD58 mRNA and the percentage of CD58 positive cells in PBMCs from patients with HBV infection were both positively correlated with serum levels of ALT and AST.

CONCLUSIONThe level of CD58 expression is related with the severity of HBV infection and the degree of liver damage.

Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; CD58 Antigens ; genetics ; Hepatitis B ; blood ; physiopathology ; Humans ; Leukocytes, Mononuclear ; metabolism ; RNA, Messenger ; analysis

A 61-year-old male patient was admitted because of unexplained abdominal pain and anemia. His past medical history was unremarkable except for having taken herbal medicine to treat facial palsy two months ago. The result of health examination performed about a month ago showed increased serum aspartate and alanine aminotransferase level, and he was diagnosed with toxic hepatitis by herbal medicine. When the patient presented to the outpatient department three weeks ago, follow-up liver function test results showed improvement but he complained of abdominal pain. Despite extensive blood chemistry tests and computed tomography, the cause of pain could not be found. After much deliberation, serum lead level and herbal medicines analysis was performed based on the fact that he took herbal medicine two months ago, and he could finally be diagnosed with lead poisoning. Since the serum lead level was high enough to be indicated for lead chelating therapy, conservative management was given. When a patient with toxic hepatitis due to herbal medication presents with abdominal pain, the possibility of lead poisoning should always be taken into consideration.
Acute Disease ; Alanine Transaminase/analysis ; Aspartate Aminotransferases/analysis ; Chemical and Drug Induced Liver Injury/*diagnosis ; Hemoglobins/analysis ; Humans ; Lead/analysis ; *Lead Poisoning ; Liver/enzymology/metabolism ; Liver Function Tests ; Male ; Middle Aged ; Plants, Medicinal/chemistry

OBJECTIVETo study the intervention effects of Jianpi Liqi Huoxue Decoction ( JLHD) on lipid peroxidative liver injury induced by alcohol.

METHODSThe rat alcoholic model of liver disease (ALD) induced by Lieber-DeCarli liquid diet was established. Thirty-two male SD rats were randomly divided into 4 groups: the normal group (n =5), the control group (n =9), the model group (n =9) and the JLHD group (n =9). From the 4th week after modeling, the rats were given JLHD or distilled water by gastrogavage respectively, and the samples of blood and liver tissues were taken out from the rats for determination by the end of the 8th week. The hepatic pathological changes were observed with HE staining; the liver injury related indices, including activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, Y-glutamyl transpeptidase (Y-GT) activity and triglyceride (TG) content in liver tissues, as well as the lipid peroxidation related indices, including malonaldehyde (MDA) content and nitric oxide synthase (NOS) activity in liver tissue, serum Fe2+ level, and the anti-peroxidation capacity related indices, including superoxide dismutase (SOD) activity, glutathion (GSH) content and reactive oxygen species (anti-ROS) activity in liver tissues were determined.

RESULTS(1) There were obvious figures of fatty degeneration and inflammatory infiltration in liver tissues of the model group. As compared with the control group, in the model group, the activity of ALT and AST, and Fe2+ content in serum, Y-GT and NOS activity, TG and MDA content in liver tissues were significantly higher (P<0. 01), while the activity of SOD, GSH and anti-ROS in liver tissues were significantly lower (P<0.01). (2) The fatty degeneration and inflammatory infiltration of liver tissues in the JLHD group were significantly lessen as compared with those in the model group; and the abnormalities of all the indexes revealed in the model rats were restored to certain extent in the JLHD group, and especially significant were the levels of ALT activity, MDA content and Fe2+ , which were nearly normal.

CONCLUSIONJLHD has significant effects against alcoholic liver injury, the acting mechanism of which is likely to be related with its anti-lipid peroxidative effect.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Glutathione ; analysis ; Lipid Peroxidation ; drug effects ; Liver ; pathology ; Liver Diseases, Alcoholic ; drug therapy ; metabolism ; pathology ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Triglycerides ; analysis

OBJECTIVESTo explore the role of TLR4 in the mechanism of hepatic ischemia/reperfusion (I/R) injury in mice.

METHODSWild-type (C3H/Heouj) mice and TLR4 deficient mice (C3H/Hej) were used to prepare the models of liver I/R injury. Partial hepatic ischemia was produced by inflow causing occlusion in the median and left lobes for 45 minutes. Blood was drawn to kill the mice at 1 hours and 3 hours after reperfusion. The blood was used to analyze aspartate aminotransferase (AST) and tumor necrosis factor-alpha (TNFalpha). TNF-alpha mRNA expression and myeloperoxidase (MPO) level in ischemic lobes was examined by northern blot and myeloperoxidase assay, respectively.

RESULTSAST levels were significantly lower in TLR4 deficient mice, compared with those in wild-type mice at both time points (661.83U/L+/-106.09U/L vs. 1215.5U/L+/- 174.03U/L, t=-6.65, P<0.01; 1145.17U/L+/-132.42U/L vs. 2958.17U/L+/-186.81U/L, t=-5.57, P<0.01). Serum TNF-alpha level was lower in TLR4 deficient mice at 3 hours after reperfusion compared with that in wild-type mice (152.39pg/ml+/-43.3 pg/ml vs. 249.12pg/ml+/-51.89pg/ml, t=-3.13, P<0.05). This difference appeared to be mediated at the gene level, since TNF-alpha mRNA expression had decreased in TLR4 deficient mice at 1 hours after reperfusion, compared with that in wild type mice (80.3+/-28.8 vs. 189.4+/-24.6, t=-3.25, P<0.05). MPO level in ischemic lobes in TLR4 deficient mice at 3 hours after reperfusion was significantly lower than that in wild type mice (F=33.49, P<0.01).

CONCLUSIONSI/R hepatic injury in TLR4 deficient mice is less than that in wild-type mice. TNF-alpha expression down-regulated at the mRNA level appears critical. These suggest that TLR4 be involved in the mechanism of hepatic ischemia/reperfusion injury in mice.

Alanine Transaminase ; blood ; Animals ; Liver ; blood supply ; metabolism ; Membrane Glycoproteins ; physiology ; Mice ; Mice, Inbred C3H ; Peroxidase ; metabolism ; RNA, Messenger ; analysis ; Receptors, Cell Surface ; physiology ; Reperfusion Injury ; etiology ; Toll-Like Receptor 4 ; Toll-Like Receptors ; Tumor Necrosis Factor-alpha ; analysis ; genetics

OBJECTIVETo establish a hepatolenticular degeneration rat model with excessive copper, and investigate the effects of excessive copper deposits in the liver on hepatocyte apoptosis and Bax and Bcl-2 expression.

METHODSRat model of hepatolenticular degeneration was established by administering forages containing 1g/kg of copper sulfate and drinking water containing 0.185% copper sulfate. Copper level in the liver and serum and alanine aminotransferase (ALT) level in serum were measured using an atomic absorption spectrophotometer. The terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL) method was used to detect hepatocyte apoptosis. Bax and Bcl-2 expression was observed by RT-PCR and imunohistochemistry staining. Quantification of positive cells was performed by image analyzer.

RESULTSWith more prolonged excessive copper ingestion, copper level in the liver and serum as well as ALT level in serum rose, and more apoptosis cells appeared in the liver. Bax and Bcl-2 expression increased significantly compared with controls fed a normal diet and progressively increased with more prolonged excessive copper ingestion. The progressively increased extent of Bcl-2 expression was lower than that of Bax expression, so the ratio of Bcl-2/Bax decreased with increasing excessive copper ingestion time.

CONCLUSIONSExcessive copper deposits in the liver can induce hepatocyte apoptosis through an up-regulation of Bax expression.

Alanine Transaminase ; blood ; Animals ; Apoptosis ; drug effects ; Copper ; toxicity ; Hepatocytes ; drug effects ; pathology ; Liver ; chemistry ; metabolism ; Male ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; bcl-2-Associated X Protein ; analysis ; genetics

OBJECTIVETo study hepatic NF-κB level following endotoxemic liver injury, and its relationship with hepatic TNF-α and IL-6 levels in young rats.

METHODSForty 18-day-old rats were randomly assigned to a normal control and an endotoxemia group. Endotoxemia was induced by lipopolysaccharide injection (LPS, 5 mg/kg). The endotoxemia group was subdivided into four groups sampled at 2, 6, 12 and 24 hrs after LPS injection (n=8 each). Pathological changes in liver cells were observed under a light microscope. TNF-α and IL-6 levels in liver tissue homogenates were measured using ELISA. Reitman-Frankel was used to measure serum ALT concentrations. NF-κB activation level in liver tissues was detected by immunohistochemistry.

RESULTSLiver tissue injury was the most obvious 6 hrs after LPS injection under the light microscope, and the damage rating of liver tissues was significantly higher in the endotoxemia group than that in the normal control group at all time points (P<0.05). ALT levels in the endotoxemia group were significantly higher than those in the normal control group 6, 12 and 24 hrs after LPS injection (P<0.05). NF-κB p65 protein expression in liver cells (percentage of nuclear positive cells) in the endotoxemia groups was significantly higher than that in the normal control group (P<0.05). TNF-α and IL-6 levels in liver tissue homogenates in the endotoxemia groups were significantly higher than those in the normal control group 6 and 12 hrs after LPS injection (P<0.05).

CONCLUSIONSEndotoxemia can cause liver injury, resulting in liver cell damage and changes in liver function. NF-κB activation is involved in endotoxemic liver injury which may be mediated by inflammatory cytokines TNF-α and IL-6 synthesis.

Alanine Transaminase ; blood ; Animals ; Behavior, Animal ; Endotoxemia ; complications ; Female ; Interleukin-6 ; analysis ; Liver ; chemistry ; pathology ; Liver Diseases ; etiology ; metabolism ; Male ; NF-kappa B ; analysis ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; analysis

The aim of this study was to observe the protective effect of water extract from Sabia parviflora on mice with acute liver injury induced by acetaminophen, and investigate its possible mechanism. Fifty-eight Kunming mice were divided into 6 groups, 8 in the normal group, 10 in the model group, 10 in the biphenyl diester group, and 10 each in the low, medium and high dose groups. After adaptive feeding for one week, the mice in normal group were intragastrically administered with an equal volume of 0.5% sodium carboxymethylcellulose sodium(CMC-Na), and the mice in other groups were intragastrically administered with corresponding drugs at 20 mL·kg~(-1) once a day. Then acetaminophen(200 mg·kg~(-1)) was administered after the above drug administration except the normal group. The behavior and signs of the experimental animals were observed every day and the samples were taken for experiments on the next day of the final administration. The liver mass and mass index were calculated. The blood was collected from the abdominal aorta and centrifuged to obtain the serum for detecting aspartate aminotransferase(AST) activity and alanine aminotransferase(ALT) activity. The liver tissue homogenate was used to detect superoxide dismutase(SOD) activity, glutathione(glutathione, r-glutamyl cysteingl+glycine, GSH) activity and malondialdehyde(MDA) content. Liver tissue was analyzed for histological analysis. The results showed that S. parviflora could alleviate the lipid peroxidation damage in the liver caused by acetaminophen, reduce the ALT and AST activities in serum, increase the levels of SOD and GSH in liver tissue, decrease the content of MDA in liver tissue, and inhibit the apoptosis. S. parviflora could also improve the live histopathological profile, protect liver cells and restore liver function. Among them, the high dose had the most significant effect and showed dose-effect relationship. This study indicated that S. parviflora had a significant protective effect on acetaminophen-induced liver injury in mice, and its mechanism may be related to its anti-oxidation effect and inhi-bitory effect on apoptosis.
Acetaminophen/toxicity* ; Alanine Transaminase/metabolism* ; Animals ; Aspartate Aminotransferases/metabolism* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Liver/enzymology* ; Malondialdehyde/analysis* ; Mice ; Oxidative Stress ; Plant Extracts/pharmacology* ; Superoxide Dismutase/metabolism*

OBJECTIVETo analyze the chemical composition and compare acute hepatotoxicity of essential oils extracted from argy wormwood leaf in Guangdong by four different methods.

METHODFour extraction methods, including hydrodistillation extraction, supercritical fluid CO2 extraction, petroleum ether ultrasonic extraction and petroleum ether microwave extraction, were employed to prepare essential oil from argy wormwood leaf in Guangdong. The products were analyzed qualitatively and quantitatively using GC-MS and GC-FID. Sixty mice were divided into 5 groups according to different essential oils and took the same dose orally, then after 5 hours, hepatic functional parameters in serum were detected such as alanine aminotransferase (ALT) and so on, and morphologic change of hepatic tissues was observed.

RESULTThe extraction rate of the four methods and identified compounds was 1.02%, 80 (hydrodistillation extraction), 2.46%, 56 (supercritical fluid CO2 extraction), 3.17%, 45 (petroleum ether ultrasonic extraction) and 3.32%, 78 (petroleum ether microwave extraction) respectively. Totally 153 compounds were identified from those essential oils. Compared with that of the control group, some hepatic functional parameters of hydrodistillation and supercritical fluid CO2 extraction groups rose significantly (P < 0.01 or P < 0.05), and hepatic tissues of hydrodistillation group were damaged significantly.

CONCLUSIONThe essential oils extracted from argy wormwood leaf by different methods may have not only different chemical composition, but also different acute hepatotoxicity, and monoterpenes and benzenes in the essential oils might induce acute hepatotoxicity.

Alanine Transaminase ; metabolism ; Animals ; Artemisia ; chemistry ; Chemical Fractionation ; methods ; Chromatography, Supercritical Fluid ; methods ; Female ; Liver ; chemistry ; drug effects ; enzymology ; Male ; Mice ; Oils, Volatile ; analysis ; isolation & purification ; toxicity ; Plant Extracts ; analysis ; isolation & purification ; toxicity ; Plant Leaves ; chemistry ; Random Allocation

OBJECTIVETo investigate the expression of farnesoid X receptor (FXR) and the effect of emodin on FXR expression in a rat model of acute cholestatic hepatitis.

METHODSNinety adult Sprague-Dawley rats were randomly divided into normal control, model, and emodin groups (n=30 each). The model and emodin groups were given alpha-naphthylisothiocyanate (ANIT) 50 mg/kg by gavage to establish an animal model of cholestatic hepatitis, while the normal control group was given an equal volume of sesame oil. The emodin group was given emodin by gavage every day from 4 days before the model was prepared until the time of sacrifice, while the model and normal control groups were given an equal volume of sodium carboxymethyl cellulose solution. At 24, 48 and 72 hours after the model was prepared, serum level of total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT), and total bile acids (TBA) were measured by Aeroset automatic biochemical analyzer, and the mRNA expression of FXR in the liver tissue was measured by real-time PCR.

RESULTSAt all time points FXR mRNA expression in the model group decreased, but serum levels of TB, DB, ALT and TBA increased significantly compared with the normal control group (P<0.05). The emodin group had significantly higher mRNA expression of FXR and significantly lower serum levels of TB, DB, ALT, and TBA compared with the model group (P<0.05).

CONCLUSIONSEmodin can significantly reduce serum levels of TB, DB, ALT, and TBA in rats with ANIT-induced cholestatic hepatitis, probably by promoting FXR expression.

Acute Disease ; Alanine Transaminase ; blood ; Animals ; Cholestasis, Intrahepatic ; drug therapy ; metabolism ; Disease Models, Animal ; Emodin ; pharmacology ; therapeutic use ; Hepatitis ; drug therapy ; metabolism ; Liver ; pathology ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear ; genetics

OBJECTIVETo investigate the factors associated with insulin resistance (IR) in patients with chronic hepatitis B virus (HBV) infection.

METHODSSixty-eight patients with mild chronic hepatitis B (MCHB) caused by HBV were recruited for study. Sixty-seven healthy individuals with no hepatitis virus infections and normal liver function were enrolled as controls. Demographic, anthropometric, clinical, and blood biochemical parameters were compared between the two groups. IR was determined by the homeostasis model assessment (HOMA-IR). The MCHB group was further divided into patients with IR (HOMA-IR: > 2.7) and patients without IR (HOMA-IR: less than 2.7). Demographic, anthropometric, clinical, and blood biochemical parameters were compared between the two sub-groups. Finally, the potential factors associated with IR were evaluated.

RESULTSCompared to the healthy controls, the MCHB patients had significantly higher serum insulin (Z = -5.451, P less than 0.01), alanine aminotransferase (ALT) (Z = -8.211, P less than 0.01) and HOMA-IR (Z = -5.631, P less than 0.01). IR was detected in 44.12% (30/68) of the MCHB patients. The levels of ALT and body mass index (BMI) were significantly different between the MCHB patients with IR and without IR (t = -2.358, and t = -3.566, P less than 0.05). There was a significant correlation between BMI, ALT, and HOMA-IR in the MCHB patients (r = 0.374, r = 0.282, P less than 0.05), but not with the HBV DNA loads (r = 0.015, P = 0.904). Binary logistic regression analysis indicated that BMI [Exp(B): 1.859, P less than 0.01] and ALT [Exp(B): 1.022, P less than 0.05] were independent risk factors of IR in MCHB.

CONCLUSIONThere is a high prevalence of insulin resistance in patients with mild hepatitis caused by chronic HBV infection. In these patients, IR is correlated with abnormal liver function and BMI, and not HBV load.

Adult ; Alanine Transaminase ; analysis ; Blood Glucose ; Body Mass Index ; Case-Control Studies ; Female ; Hepatitis B virus ; Hepatitis B, Chronic ; metabolism ; virology ; Humans ; Insulin ; blood ; Insulin Resistance ; Male ; Middle Aged ; Viral Load