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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biological assays were adopted in this study to examine the changes in serum tumour necrosis factor (TNF) activity and blood monocytic in vitro production of interleukin 1 (IL-1) in 24 severely burned patients. The myocardial and hepatic enzymes (which included aspartate aminotransferase (AST), creatine kinase (CPK), lactate dehydrogenase (LDH), alpha hydroxybutyric dehydrogenase (alpha-HBDH) and alanine amino-transferase (ALT) and some indices of biochemical metabolism (including lactic acid (LA), total protein (TP), albumin (Alb) and colloid osmotic pressure (COP)) were simultaneously measured. The results showed an evident increase in serum TNF activity and a decrease in in vitro production of IL-1 postburn; all the changes in TNF and IL-1 were correlated significantly with those of myocardial and hepatic enzymes in MOF patients. Furthermore, there were marked fever, hypoproteinaemia, tissue ischaemic and hypoxic symptoms such as hyperlacticaemia, and signs reflecting tissue hypercatabolic states. These all suggested that TNF and IL-1 might play important roles in the development of MOF.
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PMID:A preliminary exploration of the relationship between tumour necrosis factor (TNF) and monocytic in vitro production of interleukin-1 (IL-1) and internal organ dysfunction in severely burned patients. 771 14

Liposome-encapsulated hemoglobin (LEH) has been tested in animals as an oxygen-carrying red cell substitute and has been shown to be beneficial in the treatment of hemorrhagic shock. The effects of LEH on immune responses have not been studied thoroughly in any well-controlled model. Using a murine model, we evaluated nephrotoxicity and hepatotoxicity as well as immune function parameters following LEH administration. Following intravenous administration of LEH, 1) a serum spike of interleukin-6 (IL-6) occurred in mice at 4-8 hours, with no elevation of IL-1, tumor necrosis factor (TNF), or interferon-gamma (IFN-gamma); 2) the serum liver function enzymes SGOT (AST, aspartate aminotransferase) and SGPT (ALT, alanine aminotransferase) were elevated at 48 hours; 3) only a slight increase in serum antibody to bovine hemoglobin was observed; and 4) increased hematopoietic activity was observed in the spleen and bone marrow. The finding that only IL-6 but not the associated TNF, IL-1, or IFN-gamma is secreted in vivo following LEH administration is novel and may have significance in defining the mechanisms underlying specific adverse responses observed with LEH administration in animals.
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PMID:Multiple responses to administration of liposome-encapsulated hemoglobin (LEH): Effects on hematopoiesis and serum IL-6 levels. 859 72

Hepatic cytokine gene expression is independently stimulated by circulating microbial products and reductions in the cellular O2 supply. Although these stimuli occur sequentially after gram-negative bacteremia, it is unknown whether their interplay augments production of interleukin (IL)-1 by the liver. We studied the effects of intraportal Escherichia coli (EC) bacteremia and secondary constant-flow hypoxia (Po2, approximately 46 Torr for 30 min) on IL-1 alpha and IL-1 beta gene expression in ex situ buffer-perfused rat livers over 180 min (n = 67). At t = 0, normoxic EC and normal saline (NS) controls received 10(9) live EC serotype 055:B5 and 0.9% NaCl, respectively; in livers subjected to EC+hypoxia-reoxygenation (H/R) and NS+H/R, hypoxia began 0.5 h after EC or NS and was followed by 120 min of reoxygenation. Portal and hepatic venous perfusates were serially analyzed for bacterial colony-forming units, O2 uptake, and aspartate aminotransferase. At 60 min (peak hypoxia) and 180 min, cDNAs for IL-1 alpha and IL-1 beta were hybridized to whole liver RNA, and IL-1 beta protein levels in venous perfusates were assessed. Intrahepatic levels of reduced glutathione (GSH) were measured as an index of oxidative stress. Compared with normoxic EC, IL-1 alpha transcripts decreased at 180 min in EC+H/R livers (P < 0.0001) as did IL-1 beta mRNA (P < 0.05), despite similar EC clearance, GSH levels, posthypoxic O2 uptake, and aspartate aminotransferase release. Hepatic secretion of IL-1 beta likewise fell in EC+H/R vs. EC controls (P < 0.005). Prostaglandin H synthase-2 (COX-2) message accumulation was not enhanced by H/R, and indomethacin did not reverse H/R-mediated suppression of IL-1 production. In contrast, H/R-related falls in EC-induced IL-1S expression were reversed by allopurinol or catalase. Thus brief hypoxic stress of the liver causing neither GSH depletion nor functional impairment downregulates postbacteremic IL-1 expression by a mechanism involving O2 radicals but not cyclooxygenase metabolites.
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PMID:Brief hypoxic stress downregulates E. coli-induced IL-1 alpha and IL-1 beta gene expression in perfused liver. 894 69

Administration of 500 mg/kg acetaminophen (APAP) to female B6C3F1 mice resulted in well-documented pathophysiological changes in the liver manifested as increased serum concentration of liver enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and serum sorbitol dehydrogenase), centrilobular congestion, and hepatocellular degeneration and necrosis. The role of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha (IL-1 alpha), on the hepatotoxicity of APAP was examined at 4, 8, 12, and 24 hr following APAP administration. Neutralization of TNF-alpha or IL-1 alpha with specific antibodies partially prevented the hepatotoxic effects of APAP at the 4- and 8-hr time points. In addition, prior administration of anti-TNF-alpha antibodies shortened the recovery time following APAP treatment. While IL-1 receptor antagonist (IL-1ra) had only a modest protective effect against APAP-induced liver damage, as determined by serum enzyme release, IL-1ra had no effect on the degree of hepatic congestion or necrosis at any of the time points examined. On the other hand, administration of antibodies against IL-1ra exacerbated APAP-induced liver toxicity. These results suggest that TNF-alpha and IL-1 alpha play an important role in the degree of damage and recovery that the liver undergoes following APAP intoxication.
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PMID:Histopathology of acetaminophen-induced liver changes: role of interleukin 1 alpha and tumor necrosis factor alpha. 899 8

Inflammatory cytokines interleukin 1 (IL-1), IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha) have been recognized as important mediators of pathophysiological and immunological events associated with shock. These inflammatory events after hemorrhage and resuscitation are characterized by the activation of transcription regulators such as nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Curcumin, an anti-inflammatory remedy used in Indian medicine, is known to suppress NF-kappaB and AP-1 activation and also to reduce ischemia-reperfusion injuries in animal models. Therefore, the aim of this study was to determine whether administration of curcumin before hemorrhagic shock has any salutary effects on cytokines and the redox-sensitive transcription factors NF-kappaB and AP-1. mRNA levels of IL-1alpha, IL-1beta, IL-2, IL-6, IL-10, and TNF-alpha were determined by reverse transcriptase-polymerase chain reaction in rat livers collected at 2 and 24 h after hemorrhage/resuscitation. The effect of curcumin on the activation of NF-kappaB and AP-1 was determined by electrophoretic mobility shift assays. Significant increases in the levels of liver cytokines IL-1alpha, IL-1beta, IL-2, IL-6, and IL-10 were observed in the 2-h posthemorrhage/resuscitation group compared with sham animals. In contrast, oral administration of curcumin for 7 days followed by hemorrhage/resuscitation regimen resulted in significant restoration of these cytokines to depleted levels, and, in fact, IL-1beta levels were lower than sham levels. Also, the 24-h postresuscitation group showed similar patterns with some exceptions. NF-kappaB and AP-1 were differentially activated at 2 and 24 h posthemorrhage and were inhibited by curcumin pretreatment. Serum aspartate transaminase estimates indicate decreased liver injury in curcumin-pretreated hemorrhage animals. These results suggest that protection against hemorrhage/resuscitation injury by curcumin pretreatment may result from the inactivation of transcription factors involved and regulation of cytokines to beneficial levels.
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PMID:Differential regulation of cytokines and transcription factors in liver by curcumin following hemorrhage/resuscitation. 1257 24

Ginsan, a polysaccharide isolated from Panax ginseng, has been shown to be a potent immunomodulator, producing a variety of cytokines such as TNF-alpha, IL-1, IL-2, IL-6, IL-12, IFN-gamma and GM-CSF, and stimulating lymphoid cells to proliferate. In the present study, we analyzed some immune functions 1st-5th days after ginsan i.p. injection, including the level of non-protein thiols (NPSH) as antioxidants, heme oxygenase (HO) activity as a marker of oxidative stress, zoxazolamine-induced paralysis time and level of hepatic cytochrome P-450 (CYP450) as indices of drug metabolism system, and activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin level as indicators of hepatotoxicity. Ginsan in the dose of 100 mg/kg caused marked elevation (1.7 to approximately 2 fold) of HO activity, decrease of total CYP450 level (by 20-34%), and prolongation of zoxazolamine-induced paralysis time (by 65-70%), and showed some differences between male and female mice. Ginsan treatment did not seem to cause hepatic injury, since serum AST, ALT, and ALP activities and levels of total bilirubin and albumin were not changed.
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PMID:Effects of polysaccharide ginsan from Panax ginseng on liver function. 1520 59

Fumonisins are mycotoxins produced by the fugus Fusarium verticillioides, a common fungus growing on corn. Fumonisin B(1) (FB(1)) is the most toxic and prevalent fumonisin detected in corn and corn-based foods. It produces species-, gender-specific damage, and is hepatotoxic and nephrotoxic in rodents. Disruption of sphingolipid metabolism resulting from inhibition of ceramide synthase leads to alterations of cell signaling events, particularly tumor necrosis factor (TNF)alpha signal pathways and to the toxic effects of FB(1). It has been reported that FB(1) toxicity involves oxidative stress. S-adenosylmethionine (SAM) and methylthioadenosine (MTA), an intermediate metabolite in SAM metabolism, are hepatoprotective by modulating TNFalpha expression and increasing reduced glutathione (GSH) levels. The current study investigated the effects of SAM and MTA on FB(1) hepatotoxicity in C57BL/6N mice. The animals were given SAM or MTA by intraperitoneal injection of 25 mg kg(-1) body weight every 12 h when they received subcutaneous injection of 2.25 mg FB(1) kg(-1) body weight once daily for 5 days. The results showed that neither SAM nor MTA protected FB(1)-induced liver damage indicated by the increases in activities of plasma alanine aminotransferase and aspartate aminotransferase as well as the number of apoptotic hepatocytes. Both agents prevented an increase of free sphingosine but not sphinganine. Neither SAM nor MTA modified the FB(1)-induced expression of TNFalpha, interleukin (IL)-1alpha or IL-1 receptor antagonist. The decreased GSH in liver following FB(1) treatment was not protected by either agent. The data indicate that SAM and MTA are ineffective in protecting against FB(1) toxic effects.
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PMID:S-adenosylmethionine or 5'-methylthioadenosine are unable to prevent fumonisin B1 hepatotoxicity in mice despite increased oxidation in liver. 1708 Apr

Cadmium (Cd(2+)) is a heavy metal that is dispersed throughout the modern environment mainly as a result of pollution from a variety of sources. The aims of the current study were to investigate the efficacy of purified Tunisian montmorillonite clay (TMC) to adsorb Cd, to test the stability of the resulting complex under different conditions in vitro, and to utilize the rat bioassay as an in vivo model to evaluate the protective role of TMC against Cd-induced toxicity and immunodysfunction. In the in vitro study, three concentrations of TMC (0.5, 1.0 and 1.5 g/l aqueous solution) and three concentrations of CdCl(2) (25, 50 and 100 ppm) were tested. The results of the in vitro study showed that TMC had a high capacity of adsorbing Cd at different concentrations tested. The adsorption ranged from 95.7-100% of the available CdCl(2) in aqueous solutions. The complex TMC-Cd was stable at different pHs at 37 degrees C. The in vivo results indicated that treatment with CdCl(2) (2.5 mg/kg BW) for 2 weeks resulted in a significant decrease in triglycerides, total protein, creatinine, creatine kinase, immunoglobulin profile (Ig A and Ig G) and T-cell sub-types (CD3(+), CD4(+), CD8(+) and CD56(+)). Whereas, it significantly increase serum level of AST, ALT, LDH and induced degenerative changes in pro-inflammatory cytokines (TNF-alpha and IL-1). Rats treated with TMC alone (400, 600 and 800 mg/kg BW) were comparable to the control regarding all the tested parameters. The combined treatment of CdCl(2) and TMC at the lowest dose (400 mg/kg BW) showed a significant improvement of all tested parameters. It could be concluded that TMC was effective to protect against Cd hazards at a dose as low as 400 mg/kg BW. These results supported our hypothesis that TMC tightly-bind and immobilized Cd resulted in reduction of metal bioavailability in the gastrointestinal tract.
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PMID:Inactivation of cadmium induced immunotoxicological alterations in rats by Tunisian montmorillonite clay. 1746 9

IL-19, a proinflammatory cytokine, belongs to the IL-10 family. IL-19 is induced in systemic inflammatory response syndrome, but its pathophysiological function in sepsis is unclear. Our aim was to determine the roles of IL-19 in endotoxin-induced tissue damage in vivo and in vitro. We examined serum levels of IL-19 in sepsis patients and healthy volunteers, determined the in vitro effects of IL-19 on lung epithelial cells, liver cells, and neutrophils, and analyzed the tissue expression of IL-19 and its receptors in murine endotoxic shock. Electroporation-mediated gene transfer of mouse IL-19-soluble receptor plasmid DNA was used to determine the effects of IL-19 depletion in preventing endotoxic shock-induced tissue damage in mice. We found that serum levels of IL-19 were higher in patients than in healthy volunteers (n = 28, P = 0.001). IL-19 induced apoptosis in lung epithelial cells and reactive oxygen species production in liver cells in vitro. IL-19 also promoted neutrophil chemotaxis, reduced neutrophil apoptosis, and induced the production of proinflammatory cytokines and chemokines (IL-1[beta], IL-6, IL-8, CCL5, and CXCL9) in lung epithelial cells. In LPS-challenged mice, transcripts of IL-19 and its receptors were up-regulated in heart, lung, liver, and kidney tissue. Neutrophil infiltration in lung and liver tissue, and serum levels of alanine transaminase and aspartate transaminase, were lower in mice electroporated with IL-19-soluble receptor plasmid DNA before LPS treatment compared with control mice. These results suggest that up-regulated IL-19 may be involved in lung and liver tissue injury in murine endotoxic shock.
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PMID:IL-19 is involved in the pathogenesis of endotoxic shock. 1824 2

Mesenchymal stem cells (MSCs), largely present in the adult human body, represent an attractive tool for the establishment of a stem cell-based therapy for liver diseases. Recently, the therapeutic potential and immunomodulatory activity of MSCs have been revealed. Adipose tissue-derived mesenchymal stem cells (AT-MSCs), so-called adipose-derived stem cells or adipose stromal cells, because of their high accessibility with minimal invasiveness, are especially attractive in the context of future clinical applications. The goal of the present study was to evaluate the therapeutic potential of AT-MSCs by their transplantation into nude mice with CCl(4)-caused liver injury. We observed that after transplantation, AT-MSCs can improve liver functions, which we verified by changes in the levels of biochemical parameters. Ammonia, uric acid, glutamic-pyruvic transaminase, and glutamic-oxaloacetic transaminase concentrations returned to a nearly normal level after AT-MSC transplantation. These results raised the question of how AT-MSCs can achieve this. To discover the possible mechanisms involved in this therapeutic ability of AT-MSCs, in vitro production of cytokines and growth factors was analyzed and compared with MSCs from bone marrow (BM-MSCs) and normal human dermal fibroblasts (NHDFs). As a result we observed that AT-MSCs secrete interleukin 1 receptor alpha (IL-1Ralpha), IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein 1, nerve growth factor, and hepatocyte growth factor in a volume higher than both BM-MSCs and NHDFs. Thus, our findings suggest that AT-MSCs may account for their broad therapeutic efficacy in animal models of liver diseases and in the clinical settings for liver disease treatment. Disclosure of potential conflicts of interest is found at the end of this article.
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PMID:IFATS collection: in vivo therapeutic potential of human adipose tissue mesenchymal stem cells after transplantation into mice with liver injury. 1853 55


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