Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T-cell immunoregulatory cytokines influence the persistence of hepatitis C virus (HCV) chronic infection and the extent of liver damage. Th1 cytokines positively correlate with hepatic inflammation in chronic hepatitis B virus (HBV) infection. The pro-inflammatory, cytokines IL-6 and IL-18, are involved in viral clearance and in metabolic and viral hepatic diseases, respectively. The aim of this study was to evaluate the profile of Th1/Th2 cytokines in HCV and HBV hepatitis. HBV-infected patients showed higher plasma IFN-gamma levels than the HCV+ patients or the control group (p <0.0001). Plasma TNF-alpha and IL-2 were higher in HBV+ in comparison to HCV+ patients (p <0.001) or the control group (p <0.005). Plasma IL-6 and IL-18 were higher in both groups of patients compared to the control group (p <0.04). In HCV+ and HBV+ groups, IL-6 was positively correlated with the duration of the illness (p <0.01 and <0.001, respectively) and viral load (p <0.001 and <0.001, respectively), while IL-18 was positively correlated with serum ALT activity (p <0.01 and <0.001, respectively) and serum AST activity (p <0.01 and <0.001, respectively). We found that in HCV+ and HBV+ patients there are higher levels of Th1 cytokines, particularly in the course of chronic hepatitis B, and that IL-18 and IL-6 levels may have important roles as markers of both inflammation and hepatic injury, particularly in the course of hepatitis C.
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PMID:Cytokine patterns correlate with liver damage in patients with chronic hepatitis B and C. 1668 9

Major drawbacks of chemotherapeutic agents are their toxic side effects and lack of tumor specificity. Immunological and biochemical studies were here carried out to investigate protective effects of ethanolic extract of Andrographis paniculata against cyclophosphamide (CTX) induced toxicity in vivo. Intraperitoneal administration of the extract significantly increased the total WBC account (3256.5+/-196 cells/cm(2)), bone marrow cellularity (17.1+/-10.4x10(6) cells/femur) and betaesterase positive cells (849+/-23.2 cells/4000 cells) in CTX treated animals, when compared to CTX alone treated control mice. Weights of lymphoid organs such as a spleen and thymus, reduced by CTX administration, were also increased by A paniculata treatment. Reduction of GSH in liver (4.8+/-0.21nmol/mg protein) and in intestinal mucosa (13+/-0.67 nmol/mg protein) of CTX-treated controls was significantly reversed by A paniculata administration (liver: 6.4+/-0.13, intestinal mucosa: 17.11+/-0.06), with amelioration of changes in serum and liver ALP, GPT, LPO (lipid peroxidation). Histopathological analysis of small intestine also suggests that extract could reduce the CTX induced intestinal damage. The level of proinflammatory cytokine TNF-alpha, which was elevated during CTX administration, was significantly reduced by the A paniculata extract administration. The lowered levels of other cytokines like IFN-gamma, IL-2, GM-CSF, after CTX treatment were also found to be increased by extract administration.
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PMID:Ameliorating effects of Andrographis paniculata extract against cyclophosphamide-induced toxicity in mice. 1725 Apr 37

1-Bromopropane (1-BP) is used as a cleaning agent or adhesive solvent in the workplace. In the present study, the hepatotoxic and immunotoxic effects of 1-bromopropane and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. The animals were treated orally with 200, 500 and 1000 mg kg(-1) of 1-BP in corn oil for a dose response study or treated orally with 1000 mg kg(-1) of 1-BP for 6, 12, 24 and 48 h for a time course study. The hepatic and splenic contents of GSH were significantly decreased by 1-BP in a dose-dependent manner. S-propyl GSH was identified in livers following treatment with 1-BP by liquid chromatography-electrospray ionization tandem mass spectrometry. When the production of conjugates from 1-BP was investigated in livers following oral treatment with 1000 mg kg(-1) of 1-BP for 6, 12, 24 and 48 h, the GSH conjugates were detected maximally 6 h after treatment. Treatment of mice with 1-BP increased the serum activity of alanine aminotransferase dose-dependently. The oral 1-BP treatment significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular IL-2 in response to Con A in a dose-dependent manner. The present results suggested that 1-BP could cause hepatotoxicity and immunotoxicity as well as depletion of GSH content due to the formation of GSH conjugates.
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PMID:Role of glutathione conjugation in the hepatotoxicity and immunotoxicity induced by 1-bromopropane in female BALB/c mice. 1726 26

This study aims to investigate the potential role of endogenous interleukin (IL)-10 in long-term liver allograft survival induced by delayed immunosuppression (FK506 days 2-7). Liver transplantation was performed by using Dark Agouti and Lewis rats as donors and recipients, respectively. The delayed immunosuppression protocol induced indefinite allograft survival. A transient upregulation of plasma IL-10 levels was detected in the nontreatment and FK506 treatment groups. Macrophages were found to be one of the major sources of IL-10 produced from the liver allografts. Administration of IL-10-neutralizing antibody shortened the long-term isograft survival and FK506-induced indefinite allograft survival, particularly in the FK506 group. Damaged liver graft histology and increase of plasma alanine aminotransferase levels were detected in the groups with IL-10 antibody treatment. In an ex vivo setting, IL-10 recombinant protein augmented the expression of Foxp3, downregulated the expression of IL-2 and interferon gamma, and induced the generation of CD4(+)CD25(+)Foxp3(+) and CD8(+)CD25(+)Foxp3(+) cells, but this effect was blocked by the administration of IL-10 antibody. Finally, administration of IL-10 recombinant protein after the decline of endogenous IL-10 levels improved allograft survival, and a 100% long-term allograft survival was achieved by the combination of IL-10 with low-dose FK506. In conclusion, the delayed immunosuppression could induce long-term liver allograft survival in the presence of endogenous IL-10 produced by the tissue macrophages. Supplementary exogenous IL-10 administration combined with low-dose immunosuppressive drug may be a useful strategy to induce long-term liver allograft survival.
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PMID:Induction of long-term liver allograft survival by delayed immunosuppression is dependent on interleukin-10. 1739 63

An alcoholic extract of Biophytum sensitivum was studied against cyclophosphamide (CTX) induced toxicity in mice. Intraperitoneal administration of the extract with CTX significantly increased the total WBC count (3,356 +/- 236 cells/cm2), bone marrow cellularity (15.6 +/- 0.42 cells/femur) and alpha-esterase positive cells (846 +/- 30 cells) when compared to control mice treated with CTX alone. The relative organ weight of the spleen and thymus was also found to be increased after B. sensitivum administration when compared to the control mice. Reduction of GSH in liver (4.9 +/- 0.22 nmol/mg protein) and in intestinal mucosa (10.6 +/- 1.02 nmol/mg protein) of CTX treated controls was significantly reversed by B. sensitivum administration (liver: 6.5 +/- 0.18 nmol/mg protein; intestinal mucosa: 16.5 +/- 0.88 nmol/mg protein), with amelioration of changes in serum and liver ALP, GPT and lipid peroxidation. Histopathological analysis of the small intestine also suggests that B. sensitivum could reduce CTX induced intestinal damage. The level of the pro-inflammatory cytokine, TNF-alpha, which was elevated during CTX administration, was significantly reduced by the administration of B. sensitivum extract. The lowered levels of cytokines IFN-gamma, IL-2 and GM-CSF after CTX treatment were also found to be increased by B. sensitivum extract administration.
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PMID:Evaluation of the chemoprotective effect of Biophytum sensitivum (L.) DC extract against cyclophosphamide induced toxicity in Swiss albino mice. 1770 64

The alcoholic liver disease usually causes overall immunological alterations which might be attributed to hepatic disease, to ethanol action, and/or to malnourishment. In the present study, efficacy of lecithin with vitamin-B complex to treat ethanol induced immunomodulatory activity was compared with the effect of lecithin alone and tocopheryl acetate (vitamin E). Ethanol (1.6 g/kg body wt/day for 12 weeks) exposure increased thiobarbituric acid reactive substance (TBARS) level, while decreased superoxide dismutase (SOD) activity and reduced glutathione (GSH) content in whole blood hemolysate of 8-10 week-old male BALB/c mice (weighing 20-30 g). The activities of transaminase (AST and ALT) enzymes, interleukin (IL)-10 and gamma interferon (IFN-gamma) elevated, while IL-2 and IL-4 reduced in mice serum due to ethanol exposure. These suggested that oxidative stress and immunomodulatory activities were interdependent and associated with ethanol induced liver damage. Lecithin treatment significantly reduced AST (32.44%), ALT (32.09%), IL-10 (25.63%) activities and TBARS content (12.76%) compared to ethanol treated group. However, lecithin with vitamin-B complex treatment, significantly reduced AST (62.83%); ALT (61.96%); IL-10 (35.88%); IFN-gamma (22.55%) activities and TBARS content (31.58%), while significantly elevated GSH content (36.49%) and SOD activity (61.21%). Tocopheryl acetate treatment significantly reduced AST (62.83%); ALT (61.54%); IL-10 (36.35%): IFN-gamma (23.28%) activities and TBARS content (35.84%). while significantly elevated GSH content (28.76%) and SOD activity (62.42%) compared to ethanol treated group. These findings persuasively argued that lecithin with vitamin-B complex was a new promising therapeutic approach in controlling ethanol induced immunomodulatory activities involving liver damage processes. Prevention of oxidative stress with correction of nutritional deficiency caused alteration in the ethanol-induced immunomodulatory activities and associated liver diseases.
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PMID:Effect of lecithin with vitamin-B complex and tocopheryl acetate on long-term effect of ethanol induced immunomodulatory activities. 1787 44

This study analyzes how toll-like receptor 4 (TLR4) signaling in the donor organ affects the ischemia and reperfusion injury (IRI) sequel following liver transplantation. Isogenic orthotopic liver transplantations (OLTs) with rearterialization were performed in groups of wild-type (WT) and TLR4 knockout (KO) mice after donor liver preservation in University of Wisconsin solution at 4 degrees C for 24 hours. Unlike WT OLTs, TLR4-deficient OLTs transplanted to either WT or TLR4 KO recipients suffered significantly less hepatocellular damage, as evidenced by serum alanine aminotransferase levels, and histological Suzuki's grading of liver IRI. Disruption of TLR4 signaling in OLTs decreased local neutrophil sequestration, CD4+ T cell infiltration, interferon (IFN)-gamma-inducible protein 10 (CXCL10) and an intercellular adhesion molecule (ICAM-1), as well as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-2, and IFN-gamma, yet increased IL-4 and IL-10 expression. The well-functioning OLTs from TLR4 KO donors revealed attenuated activity of capase-3, and enhanced heme oygenase-1 (HO-1) expression, along with decreased levels of apoptotic endothelial cells/hepatocytes, as compared with WT OLTs with intact TLR4 signaling. Thus, the functional sentinel TLR4 complex in the donor organ plays a key role in the mechanism of hepatic IRI after OLT. Disruption of TLR4 pathway downregulated the early proinflammatory responses and ameliorated hepatic IRI. These results provide the rationale to locally modify innate TLR4 signaling in the donor organ to more efficiently control the adaptive posttransplantation IRI-dependent responses.
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PMID:Absence of toll-like receptor 4 (TLR4) signaling in the donor organ reduces ischemia and reperfusion injury in a murine liver transplantation model. 1790 30

This study was to investigate the effects of the combination of deoxynivalenol (DON) and zearalenone (ZON) on pigs. Twenty-four weaning piglets were divided into a control group fed a diet free of mycotoxins and a toxin group fed a diet containing 1 mg/kg DON and 250 microg/kg ZON. The results showed that supplementation of DON and ZON in diets had extensive effects on pigs. More specifically, DON and ZON caused levels of total protein, albumin, and globulin in sera to decrease (p < 0.05) by 14.5%, 6.5% and 11.3%, respectively, and at the same time increased (p < 0.05) the serum enzyme activities of gamma-glutamyltransferase, aspartate aminotransferase and alanine aminotransferase by 72.0%, 32.6% and 36.6%, respectively. In addition, DON and ZON decreased (p < 0.05) the level of anticlassical swine fever antibody titers by 14.8%. Real-time PCR showed that DON and ZON caused the mRNA expression levels of IFN-gamma, TNF-alpha, IL-2, to decrease (p < 0.05) by 36.0%, 29.0% and 35.4%, respectively. Histopathological studies demonstrated that DON and ZON caused abnormalities in the liver, spleen, lymph nodes, uterus, and kidney. The concentrations of DON and ZON used in this study are in line with the published critical values permitted by BML. Our study clearly put the standard and adequacy of safety measures for these toxins into question. The authors suggest that with the increasing availability of cellular and molecular technologies, it is time to revisit the safety standards for toxins in feeds so as to make feeds safer, providing consumers with safer products.
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PMID:The combination of deoxynivalenol and zearalenone at permitted feed concentrations causes serious physiological effects in young pigs. 1829 87

The aim of this study was to evaluate the hepatoprotective and anti-inflammatory effects of silybin-phospholipids and vitamin E complex (SPV complex), by determining cytokine patterns and various markers of liver disease. Forty Caucasian patients with chronic HCV infection were recruited and divided into two groups: 30 were treated with SPV complex for 3 months, while the other 10 did not receive any treatment. Ten other subjects without HCV infection but with staeatosic diagnosis were recruited and treated with SPV complex. Biochemical and hepatic principal parameters were investigated at 0 (T0) and 3 months (T3). The group of HCV patients treated showed an improvement trend of hepatic indecises and viral load, and had a significant and persistent reduction of ALT (P = 0.02) and AST serum level (P = 0.01). In this group cytokines showed a statistically significant increase of IL-2 (P = 0.03) and IL-6 were significantly reduced (P = 0.02) at T0 and T3. After the treatment the group of hepatic steatosics showed a significant decrease in ALT (P = 0.02), AST (0.008), gammaGT (0.004) alkaline phosphatase (0.05), total cholesterol (P = 0.03), fasting glucose (P = 0.008), insulinemia (0.0006), HOMA value (0.002) and C-reactive protein (CRP; 0.04). There was a significant reduction of IFN-gamma, TNF-alpha, and IL-6 (P = 0.02, 0.05 and 0.04, respectively). The data suggest that the SPV complex exerts hepatoprotective, anti-inflammatory and antifibrotic effects. This new compound may therefore be useful in clinical practice in patients with chronic hepatitis C who cannot undergo conventional antiviral therapy.
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PMID:Treatment with silybin-vitamin E-phospholipid complex in patients with hepatitis C infection. 1881 47

Tumor necrosis factor-alpha (TNF-alpha) is critically involved in a wide variety of inflammatory pathologies, such as hepatitis, via the TNF receptor-1 (TNFR1). To develop TNFR1-targeted anti-inflammatory drugs, we have already succeeded in creating a TNFR1-selective antagonistic mutant TNF-alpha (R1antTNF) and shown that R1antTNF efficiently inhibits TNF-alpha/TNFR1-mediated biological activity in vitro. In this study, we examined the therapeutic effect of R1antTNF in acute hepatitis using two independent experimental models, induced by carbon tetrachloride (CCl(4)) or concanavalin A (ConA). In a CCl(4)-induced model, treatment with R1antTNF significantly inhibited elevation in the serum level of ALT (alanine aminotransferase), a marker for liver damage. In a ConA-induced T-cell-mediated hepatitis model, R1antTNF also inhibited the production of serum immune activated markers such as IL-2 and IL-6. These R1antTNF-mediated therapeutic effects were as good as or better than those obtained using conventional anti-TNF-alpha antibody therapy. Our results suggest that R1antTNF may be a clinically useful TNF-alpha antagonist in hepatitis.
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PMID:The therapeutic effect of TNFR1-selective antagonistic mutant TNF-alpha in murine hepatitis models. 1881 54


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