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)

Hepatocyte growth factor (HGF) is a potent stimulator of DNA synthesis in cultured hepatocytes. To determine whether HGF has any activity in vivo, we have tested HGF in rats in which intrahepatic cholestasis was induced by acute administration of alpha-naphthylisothiocyanate (ANIT). The hepatotoxic effects of a single injection of ANIT were manifested 48 h later as large increases in serum bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. These biochemical changes were accompanied by widespread periportal edema, hypertrophy of bile duct epithelium, and randomly scattered areas of liquifaction necrosis in the hepatic parenchyma. The increases in bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were markedly attenuated when HGF was administered 30 min before ANIT and again at 6, 12, 24, 30, and 36 h after ANIT. In addition, this HGF dosing regimen completely prevented the occurrence of parenchymal lesions, although it had no effect on periportal histopathology. The effect of ANIT was dose dependent; a maximal response was observed at 320 micrograms/kg per injection, with an intermediate response at 105 micrograms/kg. Delaying the administration of HGF until 12 h after ANIT was as effective as when administration was begun 30 min before ANIT. Taken together these results show that HGF can prevent some aspects of ANIT hepatotoxicity.
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PMID:Reduction of alpha-naphthylisothiocyanate-induced hepatotoxicity by recombinant human hepatocyte growth factor. 144 96

The present study was designed to assess energy metabolism of steatotic grafts and to determine its relation to early graft viability. Graft biopsies were taken, and the triglyceride content was determined in 29 grafts for the assessment of steatosis. The peak aspartate aminotransferase level and the concentrations of lactate and pyruvate were strongly correlated with the triglyceride content, suggesting that steatotic grafts are more vulnerable to preservation or reperfusion injury and that glucose oxidation is inhibited postoperatively in the steatotic grafts. Ketogenesis, an alternative pathway to produce energy substrates, was not accelerated even when the steatotic grafts produced more free carnitine to enhance the beta-oxidation of fatty acids. The deterioration of energy metabolism was associated with the increase in prothrombin time ratio, hepatocyte growth factor, and hyaluronic acid that reflected graft viability. Deterioration of postperfusion energy metabolism in the steatotic grafts may be involved in the development of irreversible graft damage.
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PMID:Postperfusion energy metabolism of steatotic graft and its relation to early graft viability following liver transplantation. 950 38

There is no established model of regenerative liver resection in the baboon, and no study comparing the circulating hepatocyte growth factor (HGF) response with the DNA synthetic response after liver resection. A mean 20% partial hepatectomy (PH) was performed in 19 baboons and a sham operation comprising liver mobilisation only was performed in 20 baboons. Blood HGF levels were measured up to 5 days after either procedure, using the human HGF enzyme-linked immunosorbent assay (ELISA) kit (Otsuka, Japan). The white cell count (WCC), aspartate transaminase (AST) and bilirubin were also measured. Liver regeneration, reflected by an increase in DNA synthesis, was determined from serial liver biopsies in 23 baboons, using a tritiated thymidine assay of liver thymidine kinase (TK). Liver resection and WCC had a significant influence on circulating HGF levels. There was a linear relationship between WCC and circulating HGF levels, which was independent of PH. For a constant value of WCC, resection produced a peaking of HGF over time, with the maximal levels occurring between 2 and 3 days, compared with the linear response in HGF in sham-operated baboons. Liver damage, as reflected by AST levels, was found to have no significant influence on circulating HGF levels. The 20% PH produced a significant increase in liver TK, with maximum levels evident between 2 and 4 days. Accordingly in this baboon model of PH the increase in biologically active, circulating HGF preceded the increase in liver DNA synthesis over 5 days. This observation supports the role of HGF in hepatocyte proliferation and as an initiator of liver regeneration, and suggests that further investigation into the potential endocrine action of HGF could be studied in this established liver regenerative primate model.
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PMID:The changes in circulating hepatocyte growth factor after partial hepatectomy in the baboon. 1045 Jun 55

Hepatocyte growth factor (HGF) was reported to be effective in preventing acute graft-versus-host disease (GVHD) in a murine model. We examined serum HGF concentrations in 38 patients receiving allogeneic bone marrow transplants, and investigated the relationship of serum HGF concentrations to severity of acute GVHD. More HGF was present in sera from patients with than without acute GVHD. Serum HGF correlated significantly with grade of acute GVHD. Furthermore, serum HGF correlated with serum concentrations of C-reactive protein, gamma-glutamyltranspeptidase (GTP), and aspartate aminotransferase (AST). Serum concentrations of HGF in transplanted patients without GVHD were consistently low, while those in patients with acute GVHD increased with exacerbation. We conclude that HGF was produced during induction of the GVH reaction, and probably increased as a physiological response.
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PMID:Increased hepatocyte growth factor in serum in acute graft-versus-host disease. 1150 38

This study was conducted to determine the influence of hepatic ischemia and reperfusion (HIR) injury on liver regeneration and the effect of the deletion variant of hepatocyte growth factor (dHGF) under these conditions. Male Sprague-Dawley rats were subjected to 60 minutes of total hepatic ischemia, and two-thirds hepatectomy was performed just before reperfusion. Animals received intravenous administration of either vehicle buffer (vehicle control group) or dHGF (1 mg/kg) (HGF group) at the end of the period of hepatic ischemia and again 6 hours after reperfusion. At 8 hours after hepatectomy, plasma HGF levels in the vehicle control group were significantly lower than those in the nonischemic controls. Plasma aspartate transaminase levels in the vehicle control group reached 3,462 +/- 1,039 IU/L, but levels in the HGF group were significantly inhibited to 1,849 +/- 605 IU/L. The relative liver weight in the vehicle control group was significantly greater than in the HGF group, a finding that was implicated in focal liver necrosis with sinusoidal congestion. Less histological damage was observed in the HGF group. Twenty-four hours after hepatectomy, an increase in the relative liver weight in nonischemic controls and in the HGF group was higher than that in vehicle control group, and the 5-bromo-2?deoxyuridine (BrdU) labeling index in the HGF group was 23% versus 18% in the nonischemic controls. Administration of dHGF significantly improved the 7-day survival to 82% versus 40% in the vehicle control group. dHGF has potential benefit as a pharmacological agent to ameliorate impairment of the hepatic microcirculation and to potentiate a regeneration response in the ischemically damaged liver after hepatectomy and/or liver transplantation.
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PMID:Beneficial effect of deletion variant of hepatocyte growth factor for impaired hepatic regeneration in the ischemically damaged liver. 1220 52

Silymarin, a mixture of flavonolignans isolated from Silybum marianum, is known for its hepatoprotective properties. We investigated the expression of cytokines in mouse liver following treatment with 0, 10, 50, and 250 mg/kg of silymarin once daily for 5 days. A dose-related but insignificant decrease of circulating alanine aminotransferase and aspartate aminotransferase after silymarin treatment was observed, suggesting that silymarin treatment did not induce hepatic damage. Silymarin treatment caused significant increases in the expressions of transforming growth factor (TGF) beta1 and c-myc in liver. No significant difference was detected among these treatments in the expression of hepatocyte growth factor, interferon gamma, tumor necrosis factor alpha, and class II major histocompatibility complex. These results suggest that alterations of TGFbeta1 and c-myc expression in the liver may be involved in the hepatoprotective effects of silymarin observed in other studies.
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PMID:Physiological responses to a natural antioxidant flavonoid mixture, silymarin, in BALB/c mice: I induction of transforming growth factor beta1 and c-myc in liver with marginal effects on other genes. 1222 86

Myriocin, a fungal metabolite isolated from Myriococcum albomyces, Isaria sinclairi, and Mycelia sterilia, is a potent inhibitor of serine palmitoyltransferase (SPT), a key enzyme in de novo synthesis of sphingolipids. To evaluate the biological effects of myriocin in vivo, we investigated the levels of free sphingoid bases and expression of selected genes regulating cell growth in mouse liver. Male Balb/c mice, weighing 22 g were injected intraperitoneally with myriocin at 0, 0.1, 0.3, and 1.0 mg kg(-1) body weight daily for 5 days. Animals were euthanized 24 hours after the last treatment. Levels of plasma alanine aminotransferase and aspartate aminotransferase were not significantly altered by the treatment. A dose-dependent decrease in free sphinganine but not sphingosine was detected by high performance liquid chromatography in both liver and kidney. The decrease of free sphinganine paralleled the decrease in SPT activity. Reverse transcriptase polymerase chain reaction analysis on liver mRNA revealed an increase in expression of c-myc, but no changes in tumor necrosis factor alpha, transforming growth factor beta, and hepatocyte growth factor. Results showed that myriocin blocked de novo synthesis of sphingolipids in vivo by SPT inhibition and induced c-myc expression in liver.
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PMID:Inhibition of serine palmitoyltransferase by myriocin, a natural mycotoxin, causes induction of c-myc in mouse liver. 1518 Jan 63

In this study we sought to determine whether molecular mechanisms involved in the pathogenesis of fulminant hepatic failure are present in rabbits experimentally infected with rabbit hemorrhagic disease virus (RHDV). The activities of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, as well as bilirubin concentration, were found to be significantly increased 36 hours after infection. Infected animals also demonstrated significant decreases in factor VII activity, in the Fischer index, and in the deterioration of prothrombin time. The concentration of reduced glutathione was significantly decreased 36 hours after infection, and we noted a marked increase in the ratio of oxidized to reduced glutathione. Infected animals showed progressive decreases in liver activity of the antioxidant enzyme superoxide dismutase. Expression of hepatocyte growth factor and c-met was found to be progressively reduced from 24 hours after infection, during which time we detected no modification in messenger RNA (mRNA) levels of transforming growth factor (TGF)-alpha. TFG-beta 1 was overexpressed 24 and 36 hours after infection, and 36 hours after infection we detected a significant increase in TNF-alpha mRNA levels. Experimental RHDV infection also induced marked activation of nuclear factor-kappaB and a significant increase in inducible nitric oxide synthase mRNA levels from 24 hours after infection. Data obtained from this animal model support its usefulness in the investigation of potential novel therapeutical modalities aimed at neutralizing reactive oxygen species and hepatocyte growth inhibitors or enhancing hepatocyte responsiveness to mitogens.
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PMID:Pathogenic molecular mechanisms in an animal model of fulminant hepatic failure: rabbit hemorrhagic viral disease. 1551 90

Several reports claim that portal hypertension after living-donor liver transplantation (LDLT) adversely affects graft function, but few have assessed the impact of portal venous pressure (PVP) on graft regeneration. We divided 32 adult LDLT recipients based on mean PVP during the 1st 3 days after LDLT into a group with a PVP > or = 20 mm of Hg (H Group; n = 17), and a group with a PVP < 20 mm of Hg (L Group; n = 15). Outcome in the H Group was poorer than in the L Group (58.8 vs. 92.9% at 1 year). Peak peripheral hepatocyte growth factor (HGF) during the 1st 2 weeks was higher in the H Group (L: 1,730 pg/mL, H: 3,696 pg/mL; P < .01), whereas peak portal vascular endothelial growth factor (VEGF) level during the 1st week was higher in the L Group (L: 433 pg/mL, H: 92 pg/mL; P < .05). Graft volume (GV) / standard liver volume (SLV) was higher in the H Group (L / H, at 2, 3, and 4 weeks, and at 3 months: 1.02 / 1.24, .916 / 1.16, .98 / 1.27, and .94 / 1.29, respectively; P < .05). Peak serum aspartate aminotransferase, bilirubin levels, and international normalized ratio after LDLT were significantly higher in the H Group, as was mean ascitic fluid volume. In conclusion, early postoperative PVP elevation to 20 mm of Hg or more was associated with rapid graft hypertrophy, higher peripheral blood HGF levels, and lower portal VEGF levels; and with a poor outcome, graft dysfunction with hyperbilirubinemia, coagulopathy, and severe ascites. Adequate liver regeneration requires an adequate increase in portal venous pressure and flow reflected by clearance of HGF and elevated VEGF levels.
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PMID:Impact of portal venous pressure on regeneration and graft damage after living-donor liver transplantation. 1569 May 38

The purpose of this study was to determine the effects of short-term supplementation with the active compounds in green tea on serum biomarkers in patients with prostate cancer. Twenty-six men with positive prostate biopsies and scheduled for radical prostatectomy were given daily doses of Polyphenon E, which contained 800 mg of (-)-epigallocatechin-3-gallate (EGCG) and lesser amounts of (-)-epicatechin, (-)-epigallocatechin, and (-)-epicatechin-3-gallate (a total of 1.3 g of tea polyphenols), until time of radical prostatectomy. Serum was collected before initiation of the drug study and on the day of prostatectomy. Serum biomarkers hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, IGF binding protein-3 (IGFBP-3), and prostate-specific antigen (PSA) were analyzed by ELISA. Toxicity was monitored primarily through liver function enzymes. Changes in serum components were analyzed statistically using the Wilcoxon signed rank test. Cancer-associated fibroblasts were treated with EGCG, and HGF and VEGF protein and mRNA levels were measured. HGF, VEGF, PSA, IGF-I, IGFBP-3, and the IGF-I/IGFBP-3 ratio decreased significantly during the study. All of the liver function tests also decreased, five of them significantly: total protein, albumin, aspartate aminotransferase, alkaline phosphatase, and amylase. The decrease in HGF and VEGF was confirmed in prostate cancer-associated fibroblasts in vitro. Our results show a significant reduction in serum levels of PSA, HGF, and VEGF in men with prostate cancer after brief treatment with EGCG (Polyphenon E), with no elevation of liver enzymes. These findings support a potential role for Polyphenon E in the treatment or prevention of prostate cancer.
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PMID:Tea polyphenols decrease serum levels of prostate-specific antigen, hepatocyte growth factor, and vascular endothelial growth factor in prostate cancer patients and inhibit production of hepatocyte growth factor and vascular endothelial growth factor in vitro. 1954 90


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