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)

We investigated the spontaneous and phytohemagglutinin-stimulated production of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) by peripheral blood mononuclear cells in patients with chronic hepatitis C during treatment with interferon-alpha (IFN-alpha). Spontaneous productions of these were significantly higher in patients with chronic hepatitis C than in healthy subjects. For patients prescribed interferon, stimulated production of TNF-alpha was significantly higher in complete responders than in partial responders, but the differences were small between the other cytokine levels and outcome of IFN treatment. Spontaneous production of these cytokines was higher in patients with genotype III with complete response than in genotype III patients with a partial response, but this was not the case in patients with genotype II. There was a negative correlation between these cytokines and histological activity index. Spontaneous production of cytokines was decreased only in complete responders after the administration of interferon. These data suggest that the elevated production of cytokines in patients with chronic hepatitis C may be due to host response to the virus, and monitoring cytokines along with alanine aminotransferase and hepatitis C virus RNA during treatment may provide more precise information of the effectiveness of therapy.
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PMID:IL-1 beta and TNF-alpha produced by peripheral blood mononuclear cells before and during interferon therapy in patients with chronic hepatitis C. 860 75

In the present study, the role of albumin and high-density lipoprotein (HDL) as endotoxin (Et)-binding proteins in chronically alcohol-fed rats was studied. In acute ethanol-loaded rats, the Et clearance in the blood was slightly prolonged, and the amount of albumin and HDL- bound Et in the blood was markedly increased. In chronic ethanol-loaded rats, the Et clearance was significantly faster than that in the control, and HDL-bound Et was increased. In the chronic ethanol-fed rats with an additional 5 g/kg body weight of ethanol load, the Et clearance was much prolonged, and blood tumor necrosis factor and ALT was elevated, when HDL-bound Et was not further increased. Et-binding capacity of total proteins, albumin, and HDL in the hepatocyte culture medium were increased when the Kupffer cells were preincubated in the medium containing ethanol, and the resultant culture supernatant was added to the hepatocyte culture system. In the culture experiment in the chronic ethanol-loaded rats, such increases were not observed. These results suggest that the increase in Et-binding capacity of HDL and albumin may serve as a protective mechanism against Et in chronic ethanol-loaded rats. An addition of high-dose ethanol to these rats may lead to impaired Et binding and inactivation, which may finally result in increased endotoxicity.
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PMID:Role of albumin and high-density lipoprotein as endotoxin-binding proteins in rats with acute and chronic alcohol loading. 865 97

Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are major proinflammatory cytokines inducing the synthesis and release of many inflammatory mediators. They are involved in immune regulation, autoimmune diseases, and inflammation. Acanthoic acid, (-)-pimara-9(11),15-dien-19-oic acid, is a pimaradiene diterpene isolated from the Korean medicinal plant, Acanthopanax koreanum. When human monocytes/macrophages stimulated with silica were treated with 0.1-10 microg/ml acanthoic acid, the production of IL-1 and TNF-alpha was inhibited up to 90%, but the production of interleukin-6 (IL-6) was not inhibited at all. At these concentrations, it had no cytotoxic effect on human monocytes/macrophages. It also suppressed the production of TNF-alpha by alveolar macrophages and lymphocytes stimulated with silica. In addition, acanthoic acid inhibited the release of superoxide anion and hydrogen peroxide from human monocytes/macrophages and neutrophils. To know the antifibrotic effects of acanthoic acid, its effects on fibroblast proliferation and collagen synthesis were tested. The proliferation of NIH3T3 cells was inhibited almost completely by the addition of the culture supernatants of human monocytes/macrophages treated with acanthoic acid, but not by the addition of acanthoic acid only. In vitro and in vivo treatment with acanthoic acid reduced collagen production by rat lung fibroblasts and lung tissue. Furthermore, acanthoic acid suppressed granuloma formation and fibrosis in the experimental silicosis. Acanthoic acid reduced serum GOT and GPT in the rats with cirrhosis induced by CCl4, and it was effective in reducing hepatic fibrosis and nodular formation. Taken together, these data indicate that acanthoic acid has a potent anti-inflammatory and antifibrosis effect by reducing IL-1 and TNF-alpha production.
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PMID:Suppression of interleukin-1 and tumor necrosis factor-alpha production by acanthoic acid, (-)-pimara-9(11),15-dien-19-oic acid, and it antifibrotic effects in vivo. 866 Aug 20

C-reactive protein (CRP) is a liver-specific acute-phase protein, and its expression in hepatocyte is regulated by cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha. Although several alterations in cytokines have been found in patients with chronic viral hepatitis, it remains obscure how CRP expression is associated with progression of the disease in chronic viral infection. In the present study, CRP expression was evaluated in 45 patients with chronic hepatitis B and in 38 patients with chronic hepatitis C. By the immunohistochemical analysis, the intensity of CRP expression in hepatocyte was closely associated with the histology activity index (HAI) score in chronic hepatitis B. In contrast, the association was not found in chronic hepatitis C. When serial changes in serum levels of CRP were compared in long-term follow-up patients including 5 patients with chronic hepatitis B and 4 patients with chronic hepatitis C, serum levels of CRP fluctuated simultaneously with serum levels of alanine aminotransferase in chronic hepatitis B, whereas the correlation was not recognized in chronic hepatitis C. These results suggest that CRP expression correlates with progression of the disease in chronic hepatitis B, but not in chronic hepatitis C. It is also possible that cytokine-mediated response is more pronounced in chronic hepatitis B than in chronic hepatitis C.
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PMID:Comparative study of C-reactive protein in chronic hepatitis B and chronic hepatitis C. 872 11

Intravenous administration of LPS to rats results in the accumulation of both neutrophils and platelets in the liver and the development of midzonal hepatocellular necrosis. The development of liver injury entails contributions from both cellular and soluble mediators, including neutrophils, platelets, Kupffer cells, tumor necrosis factor-alpha (TNF-alpha), and components of the coagulation system. Much remains unknown about the interactions among these mediators in the pathogenesis of liver injury in vivo. Accordingly, we conducted studies with gadolinium chloride (GdCl3), an agent that inhibits Kupffer cell phagocytosis, to evaluate the role of Kupffer cells in lipopolysaccharide (LPS)-mediated liver injury, elevation in plasma TNF-alpha activity, thrombocytopenia, hepatic platelet accumulation, and activation of the coagulation system. Female Sprague-Dawley rats were pretreated with GdCl3-6H2O (10 mg/kg, i.v.) or saline vehicle 24 h before the administration of LPS (4 mg/kg, i.v.) or saline vehicle. In a preliminary study, this GdCl3 treatment regimen decreased the clearance of colloidal carbon from blood, indicating inhibition of Kupffer cell phagocytosis. Pretreatment with GdCl3 attenuated LPS-induced liver injury, monitored as increased plasma alanine aminotransferase and isocitrate dehydrogenase activities and histologic analysis. Electron micrographs of livers from rats treated with LPS revealed platelets within the sinusoids as well as Kupffer cells with phagolysosomes containing material resembling platelets. Pretreatment with GdCl3 attenuated LPS-induced thrombocytopenia and hepatic platelet accumulation, as measured by radiolabeled platelets. Treatment with GdCl3 did not, however, alter the elevation in plasma TNF-alpha activity or the activation of the coagulation system, as evidenced by a decreased in plasma fibrinogen concentration. These results suggest that Kupffer cells contribute to LPS-induced hepatic platelet accumulation and raise the possibility that protection against LPS-induced hepatic injury by Kupffer cell inactivation may be due at least partly to decreased deposition of platelets within the liver.
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PMID:Gadolinium chloride treatment attenuates hepatic platelet accumulation after lipopolysaccharide administration. 879 52

Tissue injury is a common occurrence in multiple organ failure, a possible clinical complication of Gram-negative bacterial sepsis. Gram-negative bacteria, in part through lipopolysaccharide (LPS), tumor necrosis factor, and other cytokines, activate neutrophils to increase oxygen consumption and produce reactive oxygen species (ROS). ROS have been suggested to play a critical role in the pathogenesis of multiple organ failure. Accordingly, we hypothesized that the susceptibility of tissues to ROS can be reduced by augmenting the antioxidant status of the affected tissues. Rats were challenged intravenously with LPS (Escherichia coli: 0111:B4) at a dose of 1 mg/kg body weight, and 0, 2, 4, or 6 h later were treated intravenously with plain liposomes or alpha-tocopherol liposomes (20 mg alpha-tocopherol/kg body weight); treated rats were then killed 24 h after LPS challenge. Animals challenged with LPS were extensively damaged in the liver, as evidenced by an increase in plasma alanine aminotransferase and aspartate aminotransferase activities, and also in the lung, as indicated by a decrease in pulmonary angiotensin-converting enzyme and alkaline phosphatase activities. The injection of LPS also resulted in increased myeloperoxidase activities in the two organs, suggestive of activation of the inflammatory response. Within the pulmonary and hepatic organs of LPS-challenged animals, the involvement of oxidative stress mechanisms was evident, because a significant decrease in reduced glutathione and an increase in lipid peroxidation were observed. In contrast, the administration of alpha-tocopherol liposomes in the post-LPS-challenge period resulted in a significant alleviation of both lung and liver injuries, evidenced by a general reversal of the altered biochemical indices toward normal among treated animals. The therapeutic effect was found to be greater when liposomal alpha-tocopherol treatment was given earlier during the development of injury. Plain liposomes administered immediately after LPS injection also protected hepatic and pulmonary tissues from injuries. However, unlike alpha-tocopherol liposomes, plain liposomes did not confer any beneficial effect when administered at later timepoints post-LPS injection. These data suggest that alpha-tocopherol, administered in a liposomal form, may serve as a potentially effective pharmacological agent in the treatment of LPS-induced tissue injuries.
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PMID:Treatment of LPS-induced tissue injury: role of liposomal antioxidants. 882 99

Hepatoprotective effect of celosian, an acidic polysaccharide isolated from the water extract of the seed of Celosia argentea, was investigated using chemical and immunological liver injury models. Celosian inhibited the elevation of serum enzyme (GPT, GOT, LDH) and bilirubin levels on carbon tetrachloride (CC1(4))-induced liver injuries in rat. In addition, the hepatoprotective effect of celosian was also observed in this model of liver injury by histopathological findings. Moreover, celosian suppressed rises in GPT or mortality on fulminant hepatitis induced by D-galactosamine/lipopolysaccharide (D-Ga1N/LPS) or Propionibacterium acnes/LPS in mice. These findings suggested that celosian is an active component in protection against chemical and immunological hepatitis and the activity was found to be a dose dependent. Celosian showed a concentration dependent inhibitory effect on lipid peroxide (LPO) generation in vitro. Though celosian did not reduce the release of tumor necrosis factor-alpha (TNF-alpha), it protected against recombinant human TNF-alpha (rhTNF-alpha)-induced liver injury in D-galactosamine sensitized mice.
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PMID:Protective effect of celosian, an acidic polysaccharide, on chemically and immunologically induced liver injuries. 886 Sep 60

To study the effect of cyclic AMP on liver dysfunction, dibutyryl cyclic AMP (DBcAMP, 15 mg/kg) was given to rats with acute hepatic failure induced by D-galactosamine (D-Gal; 500 mg/kg) and lipopolysaccharide (i.e., endotoxin) (Et; 0.5 mg/kg). The survival rate was only 7% for rats given D-Gal and Et (control group), while it was 100% for rats given seven doses of DBcAMP, and 53% for rats given two doses. The ALT level was high at 3475 +/- 488 KU in group III, while it was 242 +/- 69 KU in group I, and 376 +/- 49 KU in group II. The hepaplastin test level was decreased at 24 hr in all groups except group I, in which it was high at 55 +/- 11%. The serum tumor necrosis factor (TNF) level was 155 +/- 42 IU/ml in group I, 463 +/- 30 IU/ml in group II, and 1334 +/- 328 IU/ml in group III. The results of the blood biochemistry and liver tissue blood flow studies were better in the DBcAMP-treated groups, and the serum TNF levels were also lower in the treated groups. Histological examination of the liver showed extensive necrosis in the control group, but mild necrosis and inflammatory cell infiltration in the DBcAMP-treated groups. Therefore, treatment with DBcAMP suppressed acute hepatic failure induced by D-Gal and Et, resulting in a significant increase in the survival rate.
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PMID:Protective effects of dibutyryl cyclic AMP on acute hepatic failure in rats. 895 35

In the present study, we evaluated the role of high-density lipoprotein (HDL) as an endotoxin-binding protein in chronically alcohol-fed rats. Although the blood endotoxin level was significantly elevated in chronic ethanol-loaded rats, compared with control rats, serum tumor necrosis factor (TNF), ALT, and lactate dehydrogenase were not elevated. Serum HDL and its endotoxin-binding capacity were significantly increased in chronic ethanol-loaded rats. When Kupffer cells isolated from control and chronic ethanol-loaded rats were cultured in the medium containing 3 to 30 mg/dl HDL and endotoxin (500 ng/ml), endotoxin uptake and TNF production of Kupffer cells were decreased in proportion to the concentration of HDL in the medium. These results suggest that the increase in endotoxin-binding capacity of HDL may serve as a protective mechanism against endotoxin in chronic ethanol-loaded rats.
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PMID:Protective mechanism of high-density lipoprotein against endotoxemia in chronic alcohol ingestion. 898 37

Dimaprit, a selective histamine H2 receptor agonist, was examined in experimental models of endotoxin shock and hepatitis in mice. Injection of lipopolysaccharide (8 mg/kg i.v.) into Balb/c mice resulted in an elevation of plasma tumor necrosis factor-alpha (TNF-alpha), reaching the maximal level at 1 h post-lipopolysaccharide (1147 U/ml). Oral administration of dimaprit 200 mg/kg, 1 h prior to lipopolysaccharide challenge, inhibited the increase in plasma TNF-alpha by 71% and also the survival rate was increased to 62.5% from 8.3% in the disease control. In a mouse hepatitis model, simultaneous injection of galactosamine (700 mg/kg i.v.) and lipopolysaccharide (3 micrograms/kg i.v.) into Balb/c mice caused an increase in plasma TNF-alpha, peaking at 1 h, followed by an elevation of L-alanine aminotransferase (E.C.2.6.1.2) activity at 4 h onward. Oral administration of dimaprit 200 mg/kg, 1 h prior to galactosamine and lipopolysaccharide, reduced the increase in plasma TNF-alpha by 99% and L-alanine aminotransferase by 82%. In vitro, dimaprit dose dependently inhibited the production of TNF-alpha in mouse peritoneal macrophages and human peripheral blood monocytes stimulated with lipopolysaccharide with IC50 values of 1 microM. The decrease in TNF-alpha production by dimaprit was reversed by cimetidine, a histamine H2 receptor antagonist. Dimaprit dose dependently suppressed TNF-alpha mRNA in human peripheral blood monocytes. These results suggest that activation of the histamine H2 receptor downregulates the production of TNF-alpha, and that histamine may be an important regulator in pathological conditions in which TNF-alpha plays an important role.
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PMID:Efficacy of a selective histamine H2 receptor agonist, dimaprit, in experimental models of endotoxin shock and hepatitis in mice. 908 75


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