OBJECTIVETo investigate the expression and pathogenic relevance of angiotensin-converting enzyme 2 (ACE2) in liver fibrosis by using the rat model of CCl4-induced liver fibrosis.

METHODSThe liver fibrosis model was generated by delivering subcutaneous injections of CCl4 (dissolved in olive oil at a 2:3 ratio; injection dose: 3 ml/kg) every three days for six weeks into male Sprague-Dawley rats. Another group of rats that received simultaneous injections of olive oil alone (3 ml/kg) were used as controls. At week 0, 2, 4, or 6 after the first injection, a subset of rats from each group was sacrificed to obtain liver tissues and serum samples. Pathological analyses were carried out to detect the presence and extent of liver cell degeneration, necrosis, inflammatory cell infiltration, and collagen deposition. ACE2 and ACE gene and protein expressions were measured by real-time PCR and Western blotting, respectively. The significance of differential expression between groups and time points was assessed by t-test and one-way ANOVA or Kruskal-Wallis tests, and correlation with fibrosis was assessed by Spearman's rank correlation coefficient.

RESULTSCCl4 administration led to significantly up-regulated ACE2 mRNA levels at week 2 (3.055+/-1.034), 4 (3.545+/-1.947), and 6 (6.448+/-1.836) (vs. controls; H = 23.224, P less than 0.001). Similarly, hepatic ACE mRNA was significantly increased after the CCl4 injections (week 2: 3.055+/-1.034, week 4: 3.545+/-1.947, week 6: 6.448+/-1.836; vs. controls: F = 12.982, P less than 0.001). There was a significant correlation between the ACE and ACE2 gene expression levels (r = 0.750, P less than 0.001). Protein levels of ACE2 also showed an increasing trend following CCl4 administration (week 0: 0.034, week 2: 0.097, week 4: 0.356, week 6: 0.512). The hepatic ACE2 gene expression strongly correlated with levels of alanine aminotransferase (r = 0.669, P less than 0.0001) and aspartate aminotransferase (r = 0.815, P less than 0.0001), and with the Ishak fibrosis score (r = 0.850, P less than 0.001). Finally, there was a significant correlation between circulating ACE2 and the Ishak fibrosis score (r = 0.730, P less than 0.001).

CONCLUSIONA significant relationship exists between ACE2 gene expression and extent of liver fibrosis. ACE2 may play a crucial role in liver fibrogenesis.

Animals ; Aspartate Aminotransferases ; metabolism ; Liver ; Liver Cirrhosis ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction

The halogenated anesthetics, halothane, enflurane and isoflurane undergo biotransformation in man. They produce inorganic fluoride ion as a metabolite, which is well known as the cause of methoxyflurane induced nephrotoxicity. This study was done to investigate the rapidity and extent of biotransformation of volatile anesthetics for 2 hours of operation. Thirty patients were randomly divided into halothane, enflurane and isoflurane group according to anesthetics. Blood and urine sampling was done before operation, post-induction 10 min, 20 min, 30 min, 1 hour, 1 hour 30 min and 2 hours for the measurement of inorganic fluoride ion. Aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen and creatinine levels were measured before and 24 hours after operation. The results were as follows ; 1) The values of blood fluoride ion in halothane and isoflurane group were decreased with time during operation and there was no change in enflurane group. 2) The values of urine fluoride ion in three groups were increased with time during operation. The rate of increase was the greatest in enflurane group. 3) There were no changes in the value of AST, ALT, BUN and creatinine. The above results suggest that the biotransformation of volatile anesthetics to inorganic fluoride ion was the greatest in enflurane, but the level was insufficent to cause renal dysfunction during 3.18 hour operation.
Alanine Transaminase ; Anesthetics* ; Aspartate Aminotransferases ; Biotransformation* ; Blood Urea Nitrogen ; Creatinine ; Enflurane ; Fluorides ; Halothane ; Humans ; Isoflurane ; Metabolism ; Methoxyflurane

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

UNLABELLEDOBJECTIVE To observe the clinical efficacy by Qingying Huoxue Decoction (QHD) combined ursodeoxycholic acid (UDCA) in treating patients with early and mid-term primary biliary cirrhosis (PBC). METHODS Totally 78 patients were randomly assigned to the treatment group and the control group, 39 in each group. All patients received basic treatment and took UDCA (at the daily dose of 13-15 mg/kg). Patients in the treatment group took QHD, one dose per day. The treatment course for all was 6 weeks. Clinical efficacy, gamma-glutamyl transferase (γ-GGT), alkaline phospatase (ALP), TBIL, alanine aminotransferase (ALT), and aspartate transaminase (AST) were observed before and after treatment. RESULTS Totally 21 (53. 8%) patients obtained complete response in the treatment group, with statistical difference when compared with that of the control group (11 cases, 30. 8%). Levels of GGT, ALP, ALT, AST, and TBIL decreased in the two groups after treatment (P < 0.01). Levels of ALP, GGT, and TBIL were obviously lower in the treatment group than in the control group (P < 0.05).

CONCLUSIONSQHD combined UDCA in treating early and mid-term PBC patients was superior to the effect of using UDCA alone. It also could improve patients' liver function.

Alanine Transaminase ; metabolism ; Aspartate Aminotransferases ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Liver Cirrhosis, Biliary ; drug therapy ; Ursodeoxycholic Acid ; therapeutic use ; gamma-Glutamyltransferase ; metabolism

OBJECTIVES: Liver disease is the most common extra-intestinal manifestation of ulcerative colitis (UC), but the underlying pathogenesis is still not clarified. It is well accepted that the occurrence of UC-related liver disease has close correlation with immune activation, intestinal bacterial liver translocation, inflammatory cytokine storm, and the disturbance of bile acid circulation. The occurrence of UC-related liver disease makes the therapy difficult, therefor study on the pathogenesis of UC-related liver injury is of great significance for its prevention and treatment. Glutathione (GSH) shows multiple physiological activities, such as free radical scavenging, detoxification metabolism and immune defense. The synthesis and the oxidation-reduction all contribute to GSH antioxidant function. It is reported that the deficiency in hepatic GSH antioxidant function participates in multiple liver diseases, but whether it participates in the pathogenesis of UC-related liver injury is still not clear. This study aims to investigate the feature and underlying mechanism of GSH synthesis and oxidation-reduction function during the development of UC, which will provide useful information for the pathogenesis study on UC-related liver injury. METHODS: UC model was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS)-ethanol solution (5 mg/0.8 mL per rat, 50% ethanol) via intra-colonic administration in rats, and the samples of serum, liver, and colon tissue of rats were collected at the 3rd, 5th, and 7th days post TNBS. The severity degree of colitis was evaluated by measuring the disease activity index, colonic myeloperoxidase activity, and histopathological score, and the degree of liver injury was evaluated by histopathological score and the serum content of alanine aminotransferase. Spearman correlation analysis was also conducted between the degree of colonic lesions and index of hepatic histopathological score as well as serum aspartate aminotransferase level to clarify the correlation between liver injury and colitis. To evaluate the hepatic antioxidant function of GSH in UC rats, hepatic GSH content, enzyme activity of GSH peroxidase (GSH-Px), and GSH reductase (GR) were determined in rats at the 3rd, 5th, and 7th days post TNBS, and the protein expressions of glutamine cysteine ligase (GCL), GSH synthase, GSH-Px, and GR in the liver of UC rats were also examined by Western blotting. RESULTS: Compared with the control, the disease activity index, colonic myeloperoxidase activity, and histopathological score were all significantly increased at the 3rd, 5th, and 7th days post TNBS (all P<0.01), the serum aspartate aminotransferase level and hepatic histopathologic score were also obviously elevated at the 7th day post TNBS (all P<0.05). There was a significant positive correlation between the degree of liver injury and the severity of colonic lesions (P=0.000 1). Moreover, compared with the control, hepatic GSH content and the activity of GSH-Px and GR were all significantly decreased at the 3rd and 5th days post TNBS (P<0.05 or P<0.01), and the protein expressions of GCL, GSH-Px, and GR were all obviously down-regulated at the 3rd, 5th, and 7th days post TNBS (P<0.05 or P<0.01). CONCLUSIONS There is a significant positive correlation between the degree of liver injury and the severity of colonic lesions, and the occurrence of reduced hepatic GSH synthesis and decreased GSH reduction function is obviously earlier than that of the liver injury in UC rats. The reduced hepatic expression of enzymes that responsible for GSH synthesis and reduction may contribute to the deficiency of GSH synthesis and oxidation-reduction function, indicating that the deficiency in GSH antioxidant function may participate in the pathogenesis of UC related liver injury.
Animals ; Antioxidants ; Aspartate Aminotransferases ; Colitis/chemically induced* ; Colitis, Ulcerative/metabolism* ; Colon/pathology* ; Glutathione/biosynthesis* ; Liver/metabolism* ; Peroxidase/metabolism* ; Rats ; Trinitrobenzenesulfonic Acid

PURPOSE: The association between liver enzymes and death from external causes has not been examined. We investigated the association between serum aminotransferase levels and external-cause mortality in a large prospective cohort study. MATERIALS AND METHODS: A total of 142322 subjects of 35-59 years of age who completed baseline examinations in 1990 and 1992 were enrolled. Mortalities were identified using death certificates. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were categorized into quintiles. Sub-distribution hazards ratios and 95% confidence intervals (CIs) were estimated using a competing risks regression model in which deaths from other causes were treated as competing risks. RESULTS: Of 8808 deaths, 1111 (12.6%) were due to external causes. Injury accounted for 256 deaths, and suicide accounted for 255. After adjusting for covariates, elevated ALT and AST were significantly associated with an increased risk of all external-cause mortalities, as well as suicide and injury. Sub-distribution hazards ratios (95% CIs) of the highest versus the lowest quintiles of serum ALT and AST were, respectively, 1.57 (1.26-1.95) and 1.45 (1.20-1.76) for all external causes, 2.73 (1.68-4.46) and 1.75 (1.15-2.66) for suicide, and 1.79 (1.10-2.90) and 1.85 (1.21-2.82) for injury. The risk of external-cause mortality was also significantly higher in the fourth quintile of ALT (21.6-27.5 IU/L) than in its first quintile. CONCLUSION: Elevated aminotransferase levels, even within the normal range, were significantly associated with increased risk of all external-cause mortalities, including suicide, and injury.
Adult ; Alanine Transaminase/*blood/metabolism ; Aspartate Aminotransferases/*blood/metabolism ; Female ; Humans ; Male ; Middle Aged ; *Mortality ; *Population Surveillance ; Proportional Hazards Models ; Prospective Studies ; Republic of Korea/epidemiology ; Risk

Adolescent ; Adult ; Aged ; Aspartate Aminotransferases ; metabolism ; Case-Control Studies ; Electrocardiography ; Endosulfan ; poisoning ; Female ; Humans ; Lactate Dehydrogenases ; metabolism ; Male ; Middle Aged ; Young Adult

OBJECTIVETo study the toxicity of water extracts from the fruits of Evodia Fructus in different producing areas.

METHODCompare the toxicity of the extracts from different Evodia Fructus on mice by the methods of acute and subacute toxicity test. The mice were given the extracts for 1 d to test the maximal tolerance dose (MTD) or maximal dose and observe the acute toxic symptoms; The mice were given the extracts for 15 d and then detected the level of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride (TG). The liver index was calculated, and the liver histological changes were investigated.

RESULTThe MTD of water extracts from the fruits of Evodia Fructus is 62, 44.8, 35.84 g x kg(-1); the MTD of Evodia Fructus is 56, 44. 8, 35.84 g x kg(-1); the maximal dose of Evodia Fructus is 60, 54, 45 g x kg(-1). The toxic symptoms of the mice which had been given the nine samples were almost consistent. Compared with the control group in subacute toxicity test, the level of serum ALT and the liver index were all increased. The liver histological were changed.

CONCLUSIONWhen water extracts from the fruits of Evodia Fructus are given to mice one or more times. It may be toxic and induce liver damage. There is no significant correlation between the toxicity and Evodia orgins, while the toxicity seems to be more closely related to the producing area.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; China ; Drugs, Chinese Herbal ; administration & dosage ; metabolism ; toxicity ; Evodia ; chemistry ; Female ; Fruit ; chemistry ; Liver ; drug effects ; metabolism ; Male ; Mice ; Triglycerides ; blood

OBJECTIVE: To explore the clinical effect of Li-Dan-He-Ji in the treatment of infantile cholestatic hepatic fibrosis. METHODS: Patients who met the diagnostic criteria of infantile cholestatic hepatic fibrosis in the department of integrated traditional Chinese and Western medicine and the department of gastroenterology of Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January to December 2021 were included in the study by prospective randomized controlled trial. They were divided into the conventional treatment group and Li-Dan-He-Ji group according to the random number table. The patients in the conventional treatment group were given conventional treatment according to the guidelines. In the Li-Dan-He-Ji group, the self-made Chinese medicinal compound Li-Dan-He-Ji (prescription: Herba Artemisiae Scopariae, Fructus Forsythiae, Radix et Rhizoma Rhei preparata, Radix Polygoni Multiflori Preparata, Radix Paeoniae Rubra, Ramulus Cinnamomi, Fructus Aurantii, Rhizoma Atractylodis Macrocephalae, Fructus Schisandrae Chinensis, Carapax Trionycis, and Radix Glycyrrhizae) was given on the basis of the routine treatment, by oral, enema or nasal feeding, 60 mL each day, divided into 2 or 3 times, for 28 days. Outpatient follow-up was maintained for 4 weeks. Before and after treatment, serum liver fibrosis 4 items [type IV collagen (IV-C), hyaluronidase (HA), type III procollagen (PC III), laminin (LN)], liver function and cholestasis-related markers [total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)], liver stiffness measurement (LSM) detected by transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and liver and spleen retraction time were recorded in the two groups. RESULTS: During the observation period, a total of 40 cases of cholestatic hepatic fibrosis were treated, including 21 cases in the conventional treatment group and 19 cases in the Li-Dan-He-Ji group. Before treatment, the differences in serum liver fibrosis 4 items, serum liver function and cholestasis-related markers, oxidative stress indexes, LSM and APRI of the two groups were not statistically significant. After treatment, the liver fibrosis 4 items, liver function and cholestasis-related markers, LSM, and APRI were all significantly decreased in both groups, and the indexes in the Li-Dan-He-Ji group were significantly lower than those in the conventional treatment group [HA (ng/L): 165.81±21.57 vs. 203.87±25.88, PC III (μg/L): 69.86±9.32 vs. 81.82±7.39, IV-C (μg/L): 204.14±38.97 vs. 239.08±24.93, LN (μg/L): 162.40±17.39 vs. 190.86±15.97, TBil (μmol/L): 37.58±27.63 vs. 53.06±45.09, DBil (μmol/L): 20.55±19.34 vs. 30.08±27.39, ALP (U/L): 436.50±217.58 vs. 469.60±291.69, γ-GGT (U/L): 66.78±35.84 vs. 87.00±32.82, ALT (U/L): 64.75±50.53 vs. 75.20±50.19, AST (U/L): 77.25±54.23 vs. 96.80±59.77, TBA (μmol/L): 74.35±44.44 vs. 85.45±39.50, LSM (kPa): 5.24±0.39 vs. 7.53±3.16, APRI: 0.52±0.39 vs. 0.98±0.29, all P < 0.05]. After treatment, MDA in the two groups were significantly lower than those before treatment, and SOD and GSH were significantly higher than those before treatment. The level of SOD in the Li-Dan-He-Ji group was significantly higher than that in the conventional treatment group (kU/L: 64.56±6.69 vs. 51.58±5.98, P < 0.05). In addition, the liver retraction time (day: 20.13±10.97 vs. 24.33±13.46) and spleen retraction time (day: 25.93±13.01 vs. 29.14±14.52) in the Li-Dan-He-Ji group were significantly shorter than those in the conventional treatment group (both P < 0.05). CONCLUSIONS The use of Li-Dan-He-Ji in the treatment of cholestatic hepatic fibrosis can effectively improve the indicators of cholestasis, hepatic fibrosis, oxidative stress and clinical symptoms in children.
Child ; Humans ; Prospective Studies ; Cholestasis/pathology* ; Liver ; Liver Cirrhosis/drug therapy* ; Bilirubin/pharmacology* ; Oxidative Stress ; Aspartate Aminotransferases/metabolism* ; Superoxide Dismutase/metabolism*

OBJECTIVETo investigate the effects of escharectomy during shock stage on tissue high mobility group box-1 protein (HMGB1) expression and balance of pro-/anti-inflammatory cytokines, and to elucidate the potential mechanism underlying beneficial effect of early escharectomy after severe burns.

METHODSWistar rats inflicted by 30% full-thickness thermal injury were randomly divided into thermal injury group, 24 h escharectomy group and 72 h escharectomy group, in which escharectomy were performed at 24 and 72 h postburn, respectively. Gene expression of HMGB1, interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) in liver and lungs was detected with reverse-transcription PCR, and protein levels of IL-10 and TNF-alpha in liver and lung tissues were measured by ELISA. The plasma AST and ALT contents, and pulmonary myeloperoxidase (MPO) activity were also assayed.

RESULTSThe mRNA expression of HMGB1 and TNF-alpha in liver and lungs was up-regulated on postburn day 2, with IL-10 over-expression on postburn day 8. In the 24 h escharectomy group, HMGB1 and TNF-alpha mRNA expression in liver and lungs was down-regulated on postburn day 4, and IL-10 expression returned to normal range on postburn day 8, while the down-regulation of HMGB1, TNF-alpha and IL-10 were not noted in the 72 h escharectomy group. There were two peaks in liver TNF-alpha protein levels appearing on postburn days 2 and 8, respectively, with an unexpected marked decrease on day 4 in thermal injury controls, yet liver TNF-alpha levels maintained in normal range in animals of 24 h and 72 h escharectomy groups. The ratios of TNF-alpha to IL-10 protein levels in liver tissue were significantly increased on postburn days 2 and 4 (P = 0.0001 and 0.002, respectively), while escharectomy during shock stage markedly reduced hepatic TNF-alpha to IL-10 ratios (P = 0.0008 and 0.040, respectively). No significant changes in TNF-alpha protein levels in lung tissue were observed. Additionally, plasma AST as well as ALT contents, and pulmonary MPO activity were markedly decreased on postburn days 4 and 8 in the 24 h escharectomy group compared to the 72 h escharectomy group or thermal injury controls (P < 0.05).

CONCLUSIONSEscharectomy during burn shock stage could inhibit the over-expression of both early and late inflammatory mediators, and maintain the balance of pro-/anti-inflammatory response, thereby improving multiple organ functions in rats following severe burns.

Alanine Transaminase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Burns ; complications ; surgery ; HMGB1 Protein ; genetics ; metabolism ; Interleukin-10 ; genetics ; metabolism ; Liver ; enzymology ; metabolism ; Lung ; enzymology ; metabolism ; Male ; Peroxidase ; metabolism ; Rats ; Rats, Wistar ; Shock, Traumatic ; etiology ; Tumor Necrosis Factor-alpha ; genetics ; metabolism