Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver biopsy is thought mandatory for management in patients with hepatitis C virus infection (HCV) especially for histopathological grading and staging of the disease to assess suitability for treatment and monitoring disease progression. However, tracking of liver disease progression can't rely on repeated biopsies. The study aimed to evaluate two significant items, we try to develop and validate a non-invasive predictive tool to assess hepatic necro-inflammation and fibrosis. Also, to determine factors that associate severity of hepatic pathology in HCV infected Egyptian patients particularly at Sharkia G. The study included 109 patients with detectable HCV by Real Time-PCR. The patients were classified into three different pathological stages and grades according to the new concept of histopathoglical staging and grading. The different clinical, biochemical, virological and ultra-sonographic parameters were assessed and analyzed and the variables that showed significant association with histopathological staging and grading were included in multivariate logistic regression analysis. The regression model revealed that, platelet count, matrix metalloproteinase-9 (MMP-9), portal vein diameter, splenic longitudinal axis, alanine transaminase, aspartate transaminase and viral load were the factors that add significance to the model in decreasing order of significance. From these findings we generate a new score ranged from 0-9. The score model was applied to our patients to assess its validity where it proved to be accurate in discriminating patients with mild inflammation and fibrosis (sensitivity 81.8%, specificity 80.5% and accuracy 80.7%) and more accurate in detecting patients with cirrhosis (specificity 96.6%, sensitivity 80% & accuracy 93.6%) but less accurate in detecting patients with moderate to severe fibrosis (specificity 66.7%, sensitivity 68.7% & accuracy 67.9%). Also the results revealed that, co-infection with schistosomiasis, old age > or = 45 years and positive history of blood transfusion as a source of infection was significantly associated with severe hepatic pathology. It is concluded that, the score model can't completely replace liver biopsy but at least it could be used to substantially reduce the number of liver biopsies done in patients with HCV infection in assessing disease progression during follow up. Also, it can be used to make decisions about treatment in patients who have contraindications to or who refused liver biopsy. Co-infection with schistosomiasis, age > or = 45 and positive history of blood transfusion in patients with HCV warrant special attention with more intensive follow up. These factors may play a major role in forecasting the course of HCV as well as in determining the therapeutic approach in each case.
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PMID:Non-invasive markers and predictors of severity of hepatic fibrosis in HCV patients at Sharkia Governorate, Egypt. 1512 53

Laboratory tests for the noninvasive diagnosis of liver fibrosis were studied extensively in the past. However, no test is yet accepted to replace liver biopsy as the gold standard. The establishment of widely accepted semiquantitative histologic scoring systems for the grading and staging of chronic liver disease (e.g., Ishak, Metavir and Scheuer) was paralleled by a significant upturn of research in circulating markers of liver fibrosis. We are now experiencing the renaissance of standard clinical chemistry markers, which are assembled to multiparameter scores (e.g., aspartate aminotransferase-to-platelet ratio index, FibroTest, Forns' index). These scores still require comprehensive evaluation in comparison with histology. Better understanding of the pathophysiology of liver fibrosis provided new options regarding circulating markers of hepatic matrix metabolism (e.g., hyaluronic acid, laminin, matrix metalloproteinase-2, aminoterminal propeptide of procollagen type III and tissue inhibitors of metalloproteinases-1). Several promising studies have been published to date. Thus, a redefinition of the role of liver biopsy is expected in the foreseeable future.
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PMID:Noninvasive diagnosis of fibrosis in chronic liver disease. 1534 64

Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of detoxication, antioxidation, and antimutation. In this study, we evaluated the antihepatotoxic effect of PBL extract on the carbon tetrachloride (CCl(4))-induced liver injury in a rat model. Fibrosis and hepatic damage, as reveled by histology and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were induced in rats by an administration of CCl(4) (8%, 1 ml/kg body weight) thrice a week for 4 weeks. PBL extract significantly inhibited the elevated AST and ALT activities caused by CCl(4) intoxication. It also attenuated total glutathione S-transferase (GST) activity and GST alpha isoform activity, and on the other hand, enhanced superoxide dismutase (SOD) and catalase (CAT) activities. The histological examination showed the PBL extract protected liver from the damage induced by CCl(4) by decreasing alpha-smooth muscle actin (alpha-sma) expression, inducing active matrix metalloproteinase-2 (MMP2) expression though Ras/Erk pathway, and inhibiting TIMP2 level that consequently attenuated the fibrosis of liver. The data of this study support a chemopreventive potential of PBL against liver fibrosis.
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PMID:Protection effect of piper betel leaf extract against carbon tetrachloride-induced liver fibrosis in rats. 1667 62

The aim of the study was to examine the effects of epigallocatechin-3-gallate (EGCG) on hepatic fibrogenesis and on cultured hepatic stellate cells (HSCs). The rat model of carbon tetrachloride (CCl(4))-induced hepatic fibrosis was used to assess the effect of daily intraperitoneal injections of EGCG on the indexes of fibrosis. Histological and hepatic hydroxyproline examination revealed that EGCG significantly arrested progression of hepatic fibrosis. EGCG caused significant amelioration of liver injury (reduced activities of serum alanine aminotransferase and aspartate aminotransferase). The development of CCl(4)-induced hepatic fibrosis altered the redox state with a decreased hepatic glutathione and increased the formation of lipid peroxidative products, which were partially normalized by treatment with EGCG, respectively. Moreover, EGCG markedly attenuated HSC activation as well as matrix metalloproteinase (MMP)-2 activity. In cultured stellate cell, the expression of MMP-2 mRNA and protein were substantially reduced by EGCG treatment. Concanavalin A-induced activation of secreted MMP-2 was inhibited by EGCG through the influence of membrane type 1-MMP activity. These results demonstrate that administration of EGCG may be useful in the treatment and prevention of hepatic fibrosis.
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PMID:Green tea polyphenol epigallocatechin-3-gallate inhibits oxidative damage and preventive effects on carbon tetrachloride-induced hepatic fibrosis. 1748 82

In the course of the investigation of effects of newly synthesized matrix metalloproteinase inhibitors (MMPIs), FYK-1388, FYK-1352 and F61-1008, which have strong and broad matrix metalloproteinase (MMP) inhibitory activity, on wound healing in streptozotocin (STZ)-induced diabetic rats, strong reducing effects on serum triacylglycerol (TG) have been found. Namely, when examined using breaking wound strength as an index, MMPIs did not significantly facilitate wound healing in STZ-induced diabetic rats. Unexpectedly, however, the treatment of STZ-induced diabetic rats with MMPIs markedly lowered the serum level of TG without changing the blood glucose level. Among these compounds tested, FYK-1388 was the most effective, and the compound reduced serum concentrations of TG and cholesterol and levels of very low-density lipoprotein (VLDL)-TG and low density lipoprotein (LDL)-cholesterol in a dose-dependent manner. FYK-1388 did not affect serum levels of free fatty acids, high-density lipoprotein (HDL)-cholesterol, aspartate aminotransferase and alanine aminotransferase, mass of body fat, liver weights, and hepatic contents of TG and cholesterol. Moreover, treatment of Zucker fa/fa rats with FYK-1388 lowered serum levels of TG and cholesterol without changing blood levels of glucose and insulin. Since the structures of these MMPIs markedly differ from those of the hypotriglyceridemic drugs that are used clinically, it seems plausible that these MMPIs could be used as a new type of hypotriglyceridemic drug.
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PMID:Reducing effect of matrix metalloproteinase inhibitors on serum triacylglycerol in streptozotocin-induced diabetic rats and Zucker fa/fa rats. 1766 4

Glycyrrhizin, a biological active compound isolated from the liquorice root, has been used as a treatment for chronic hepatitis. We have examined the involvement of matrix metalloproteinase (MMP)9 in the development of lipopolysaccharide (LPS) and D-galactosamine (GalN)-induced liver injury in mice. We also investigated the effect of glycyrrhizin on expression of MMP-9 in this model. Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased after LPS/ GalN treatment. Expression of MMP-9 mRNA and protein was markedly up-regulated in liver tissues 6-8 h after LPS/GalN treatment. Pretreatment with glycyrrhizin (50 mg kg(-1)) and the MMP inhibitor (5 mg kg(-1)) suppressed increases in serum levels of ALT and AST in mice treated with LPS/GalN. Furthermore, glycyrrhizin inhibited levels of both mRNA and protein for MMP-9. Immunohistochemical reaction for MMP-9 was observed in macrophages/monocytes infiltrated in the inflammatory area of liver injury. Glycyrrhizin reduced the infiltration of inflammatory cells and immunoreactive MMP- 9 in liver injury. The results indicated that MMP-9 played a role in the development of LPS/GalN- induced mouse liver injury, and suggested that an inhibition by glycyrrhizin of the acute liver injury may have been due to a down-regulation of MMP-9.
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PMID:Glycyrrhizin prevents of lipopolysaccharide/D-galactosamine-induced liver injury through down-regulation of matrix metalloproteinase-9 in mice. 1825 Oct 86

Enterohemorrhagic Escherichia coli (EHEC) induces hemorrhagic colitis and hemolytic uremic syndrome (HUS). Morbidity and mortality are increased in HUS patients with neurologic complications. To determine the pathogenesis of the central nervous system (CNS) involvement in HUS by EHEC, we determined the serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNFR1), IL-10, interferon-gamma (IFN-gamma), IL-2, IL-4, soluble E-selectin (sE-selectin), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) during the acute stage in children with HUS with or without CNS involvement. Serum concentrations of IL-6, IL-10, sTNFR1, sE-selectin, MMP-9, and TIMP-1, but not TNF-alpha, IFN-gamma, IL-2, or IL-4, were significantly higher in patients with HUS with encephalopathy compared with controls. Serum IL-6, sTNFR1 and TIMP-1 concentrations were significantly higher in patients with HUS with encephalopathy compared with those with HUS without encephalopathy (P=0.031, P=0.005, and P=0.007, respectively) and those with acute colitis without HUS (P=0.011, P<0.001, and P=0.005, respectively). There were no significant differences in hemoglobin, platelet counts, leukocyte counts, or serum concentrations of IL-10, sE-selectin, MMP-9, aspartate aminotransferase, lactate dehydrogenase, blood urea nitrogen, creatinine, or C-reactive protein between the HUS patients with and without encephalopathy. Our preliminary study suggests that serum IL-6, sTNFR1 and TIMP-1 levels, particularly sTNFR1 and TIMP-1, are important for predicting neurological complications in patients with HUS.
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PMID:Soluble tumor necrosis factor receptor 1 and tissue inhibitor of metalloproteinase-1 in hemolytic uremic syndrome with encephalopathy. 1841 Sep 71

The pathophysiological mechanisms of thioacetamide (TAA)-induced hepatic fibrogenesis are not yet fully understood. In particular, the role of hepatic stellate cells (HSCs) remains unclear. We therefore examined proliferation and transdifferentiation of HSC as well as the underlying molecular mechanisms in TAA-induced fibrosis. Hepatic fibrogenesis was induced in mice by addition of TAA to drinking water. Liver damage was determined by assessment of alanine aminotransferase and aspartate aminotransferase levels, and measurement of collagen deposition. Additionally, expression patterns of alpha-smooth muscle actin, glial fibrillary acidic protein (GFAP, specific hepatic biomarker for HSC), cysteine- and glycine-rich protein 2 (CRP2, specific marker of HSC transdifferentiation), tissue inhibitor of metalloproteinases-1, matrix metalloproteinase-9 (MMP-9), interleukins (IL-1beta, IL-6), platelet-derived growth factors (PDGF-B, PDGF-D) , tumor necrosis factor (TNF)-alpha, and (transforming growth factor (TGF)-beta1 were assessed by real-time PCR. Transcription of GFAP and CRP2 were transiently upregulated during TAA-induced fibrogenesis (punctum maxima (p.m.) week 10 for GFAP and week 14 for CRP2). Similar transient expression patterns were demonstrated for IL-1beta, IL-6, TGF-beta1, and PDGF-B (p.m. week 12) whereas TNF-alpha and PDGF-D continuously increased with ongoing liver injury. In particular, not only neutrophil granulocytes, but also macrophages and leukocytes served as a major source for MMP-9 expression. GFAP and CRP2 expression patterns demonstrated transiently increased HSC-activation during TAA-induced hepatic fibrogenesis. The rate of increase of transcription of GFAP correlated best with PDGF-B, whereas CRP2 levels correlated with PDGF-B, PDGF-D, and IL-1beta expression. This study demonstrates for the first time that transiently increased activation patterns of HSC are observed in toxically induced hepatic fibrosis. Thus, TAA in drinking water is an effective and elegant model to induce reproducible states of liver fibrosis without parenchymal damage in mice.
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PMID:Activation of hepatic stellate cells is associated with cytokine expression in thioacetamide-induced hepatic fibrosis in mice. 1879 50

The present study was designed to compare the cardioprotective effects of the combination of lisinopril with growth hormone over lisinopril alone in doxorubicin (Dox)-induced cardiomyopathy in rats. Forty male Wister albino rats were divided into 4 groups: group 1, control group; group 2, received Dox; group 3, received lisinopril + Dox; and group 4, received lisinopril + Dox + growth hormone. Dox (cumulative dose) was administered to rats in 6 equal intraperitoneal injections over a period of 2 weeks. Histopathological changes and plasma aspartate aminotransferase, lactate dehydrogenase, and creatine kinase and plasma levels of matrix metalloproteinase (MMP)-2, tissue inhibitor matrix metalloproteinase (TIMP)-1, and cardiac inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) expression were determined 9 weeks after the first dose of Dox. Dox produced cardiac structural injury and significant elevation in plasma levels of cardiac enzymes, MMP-2, and cardiac iNOS mRNA expression together with significant reduction in plasma TIMP-1 level. Lisinopril significantly decreases plasma MMP-2 level and cardiac iNOS mRNA expression by 13% and 15%, respectively, in group 3 compared with 36% and 47%, respectively, in group 4 as compared with group 2. In addition, compared with Dox group, lisinopril significantly increases plasma TIMP-1 level by 23% compared with 49% in group 4. We can conclude that the combination of lisinopril and growth hormone produced better cardioprotective effect against Dox-induced cardiomyopathy. This effect may be attributed on their antiremodeling actions by regulating plasma MMP-2/TIMP-1 levels and to the reduction of cardiac iNOS mRNA expression.
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PMID:How to protect doxorubicin-induced cardiomyopathy in male albino rats? 2005 77

Our previous study found that Chinese yellow wine could inhibit the production of homocysteine (HCY) induced extracellular matrix metalloproteinase-2 (MMP-2) in the cultured rat vascular smooth muscle cells. Little is known about the relationship between Chinese yellow wine and atherosclerosis or MMP-2 in vivo. Thirty-two LDL Receptor knockout mice on a high-fat and L-methionine diet developed plasma hyperhomocysteinemia and atherosclerosis. They were randomly divided into yellow wine group (n = 8), red wine group (n = 8), ethanol group (n = 8), and control group (n = 8), they were sacrificed after 14 weeks. There were no significant differences with plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in the four groups. Plasma HCY was significantly decreased in the yellow wine group compared to the other three groups (P < 0.01). Yellow wine and red wine groups significantly reduced the atherosclerosis lesion area compared to ethanol and control groups (P < 0.001). However, there was no significant discrepancy between the yellow wine group and red wine group. Compared to the control group and ethanol group, the production of MMP-2 reduced 26.8% and 23.6% in the aortic sinus and the activation of MMP-2 reduced 32.6% and 27.3% in the aortic arch in the yellow wine group; the production of MMP-2 reduced 25.7% and 22.4% in the aortic sinus and the activation of MMP-2 reduced 30.2% and 26.6% in the aortic arch in the red wine group. These results suggest that Chinese yellow wine and red wine can inhibit MMP-2 and improve atherosclerosis, and maybe both Chinese yellow wine and red wine have beneficial effects on cardiovascular disease by inhibiting MMP-2.
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PMID:Chinese yellow wine and red wine inhibit matrix metalloproteinase-2 and improve atherosclerotic plaque in LDL receptor knockout mice. 2037 Jul 96


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