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)

In a recent study in rats, alanine aminotransferase (ALT), the preferred plasma biomarker of hepatocellular injury in rats, was ineffective at detecting marked hepatic necrosis produced by acetaminophen (Human and Experimental Toxicology 19, 277-83, 2000). In contrast, glutamate dehydrogenase (GLDH) was markedly elevated. Accordingly, these enzymes were comprehensively evaluated as plasma biomarkers of hepatocellular injury in rats using several other models of hepatic injury, including partial hepatectomy and exposure to methapyrilene, dexamethasone, cyproterone, isoniazid, lead nitrate, and Wyeth-14643. Other enzymes also evaluated were aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), and the hepatobiliary marker alkaline phosphatase (ALP). Compared to plasma ALT increases, plasma GLDH increases were up to 10-fold greater, up to 3-fold more persistent, and occurred at times following hepatocellular injury when plasma ALT was not increased. Plasma GLDH activity was not inhibited by the test compounds, whereas ALT was substantially inhibited by both isoniazid and lead nitrate. While plasma GLDH activity was unaffected by induction, ALT was induced by cyproterone and dexamethasone, and ALP was induced by Wyeth-14643 and partial hepatectomy. GLDH was concluded to be a more effective biomarker of acute hepatic injury than ALT, AST, SDH or ALP in the rat, based primarily on the large increase following hepatocellular injury, prolonged persistence in the blood following injury, high sensitivity for detection of injury (including pre-necrotic injury), high tissue specificity, and lower susceptibility to inhibition or induction.
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PMID:Advantages of glutamate dehydrogenase as a blood biomarker of acute hepatic injury in rats. 1214 42

The efficacy of Tiron (4,5-dihydroxybenzene 1,3-disulfonic acid disodium salt) was examined in the treatment of beryllium-induced maternal and developmental toxicity in rats. Single administration of beryllium nitrate at a dose of 50 mg/kg (i.m.) on day 13 of gestation caused reductions in fetal and placental weights, the number of implantation sites and number of corpora lutea, as well as causing post-implantation loss, stunted growth, increase in the number of resorptions, and also a disturbed sex ratio. Maternal toxicity was demonstrated by reduction in body weight gain. Administration of beryllium also showed significant alteration in the hematological and biochemical indices of the mother as well as the fetus. Marked decreases were recorded in hemoglobin percentage, blood sugar levels, serum protein contents and serum alkaline phosphatase activity. By contrast, significant elevation was found in the activity of transaminases (aspartate aminotransferase and alanine aminotransferase). Tissue protein contents, glycogen contents, activities of alkaline phosphatase, adenosine triphosphatase and succinic dehydrogenase of kidney, lungs and uterus, and maternal and fetal liver all showed significantly decreased values after beryllium exposure, and remarkable elevation was observed in acid phosphatase, glucose-6-phosphatase and hepatic lipid peroxidation. These parameters were restored considerably with administration of 471 mg/kg i.m. Tiron from days 14 to 18 of gestation. Atomic absorption spectrophotometry also revealed a high concentration of beryllium in different organs of pregnant rats. Interestingly, a small amount of metal ion was also detected in the fetus and reduced accumulation of beryllium was noticed after Tiron treatment.
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PMID:Protective effect of Tiron (4,5-dihydroxybenzene-1,3-disulfonic acid disodium salt) against beryllium-induced maternal and fetal toxicity in rats. 1218 11

Ischemic preconditioning (IPC) may increase the hepatic tolerance of ischemic injury during liver surgery and transplantation via nitric oxide (NO) formation. This study investigates the effect of IPC on hepatic tissue oxygenation and the role of NO stimulation and inhibition on the preconditioning effect in the rat liver. Study groups had 1) sham laparotomy; 2) 45-min lobar liver ischemia and 2-h reperfusion (IR); 3) IPC with 5-min ischemia and 10-min reperfusion before IR; 4) L-arginine before IR; and 5) Nw-Nitro-L-arginine methyl ester (L-NAME) + IPC before IR. Hepatic tissue oxygenation was monitored by near-infrared spectroscopy. Plasma alanine aminotransferase and plasma nitrite/nitrate were measured. Following IR there was significant decrease in oxyhemoglobin and cytochrome oxidase and an increase in deoxyhemoglobin (PA redox state, PL-arginine did not attenuate the impairment in hepatic tissue oxygenation after IR (P>0.05 vs IR). In contrast, inhibition of NO synthesis blocked the effect of IPC and further impaired tissue oxygenation (decreased cytochrome oxidase CuA redox state and increased deoxyhemoglobin, both PL-arginine and increased by NO blockade with L-NAME (Plasma ALT, all P< 0.05 vs IR). Hepatic tissue oxygenation correlated significantly with ALT and plasma nitrite/nitrate. Ischemic preconditioning significantly improved hepatic intra cellular oxygenation and reduced hepatocellular injury. NO stimulation reduced hepatocellular injury, whereas inhibition of nitric oxide synthesis blocked the effect of IPC and reduced tissue oxygenation and increased hepatocellular injury.
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PMID:The relationship of hepatic tissue oxygenation with nitric oxide metabolism in ischemic preconditioning of the liver. 1220 3

Hepatotoxicity was investigated, using plasma collected before and during treatment, in 16 human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients who responded to highly active antiretroviral therapy (HAART), during a retrospective longitudinal study. Eleven patients experienced hepatotoxicity (i.e., a >3-fold increase in alanine aminotransferase level) while receiving HAART, including 4 patients with clinical hepatitis. Control subjects were 5 patients without hepatotoxicity. Markers of HCV-specific immune responses (HCV core-specific immunoglobulin G [IgG] antibody), T cell activation (soluble [s] CD26 dipeptidyl peptidase IV [DPP IV] enzyme activity), and inflammation (nitrate/nitrite and soluble tumor necrosis factor receptor I [sTNFRI] levels) were correlated with liver damage and immune reconstitution. All patients with hepatotoxicity had increased HCV core-specific IgG antibody and sCD26 (DPP IV) activity but did not have increased nitrate/nitrite or sTNFRI levels. Hepatotoxicity without clinical hepatitis was associated with increased CD8 T cell counts. Thus, hepatotoxicity in HIV-HCV-coinfected patients who respond to HAART is associated with increased HCV-specific immune responses and T cell activation.
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PMID:Association of increased hepatitis C virus (HCV)-specific IgG and soluble CD26 dipeptidyl peptidase IV enzyme activity with hepatotoxicity after highly active antiretroviral therapy in human immunodeficiency virus-HCV-coinfected patients. 1240 69

1. The purpose of this study was to investigate the protective effects of defibrotide, a single-stranded polydeoxyribonucleotide, on ischaemia-reperfusion injury to the liver using a rat model. 2. Ischaemia of the left and median lobes was created by total inflow occlusion for 30 min followed by 60 min of reperfusion. Hepatic injury was assessed by the release of liver enzymes (alanine transferase, ALT and lactic dehydrogenase, LDH). Hepatic oxidant stress was measured by superoxide production, lipid peroxidation and nitrite/nitrate formation. Leukocyte-endothelium interaction and Kupffer cell mobilization were quantified by measuring hepatic myeloperoxidase (MPO), polymorphonuclear leukocyte adherence to superior mesenteric artery (SMA) and immunostaining of Kupffer cell. 3. Defibrotide treatment resulted in a significant inhibition of postreperfusion superoxide generation, lipid peroxidation, serum ALT activity, serum LDH activity, MPO activity, serum nitrite/nitrate level, leukocyte adherence to SMA, and Kupffer cell mobilization, indicating a significant attenuation of hepatic dysfunction. 4. A significant correlation existed between liver ischaemia/reperfusion and hepatic injury, suggesting that liver ischaemia/reperfusion injury is mediated predominantly by generation of oxygen free radicals and mobilization of Kupffer cells. 5. We conclude that defibrotide significantly protects the liver against liver ischaemia/reperfusion injury by interfering with Kupffer cell mobilization and formation of oxygen free radicals. This study provides strong evidence that defibrotide has important beneficial effects on acute inflammatory tissue injury such as that occurring in the reperfusion of the ischaemic liver.
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PMID:Effects of defibrotide, a novel oligodeoxyribonucleotide, on ischaemia and reperfusion injury of the rat liver. 1242 25

Nitric oxide (NO), a recently discovered free radical, is overproduced in liver cirrhosis. Hepatitis C virus (HCV) might increase NO levels via increased inducible NO synthase (iNOS). This work was carried out to study the effect of HCV-induced liver cirrhosis on NO levels among Egyptian patients. The study included 46 patients with liver cirrhosis, and 30 healthy individuals of matched age and sex. NO levels determined as the stable endproduct nitrate, showed a statistically significant increase among patients compared to the control group (P < 0.001). Furthermore, NO levels increased proportionally with the severity of liver cirrhosis as assessed by Child's classification (P < 0.05). Moreover, schistosomial infection enhanced NO levels in cirrhotic patients with HCV infection compared to non-bilharzial patients (P < 0.001). Polymerase chain reaction (PCR) and branched DNA assays were used for detection of HCV RNA positivity, and measurement of the virus load, respectively. Both showed a positive correlation with the NO levels (P < 0.001). At a nitrate cutoff value of 70 micromol/L, the sensitivity and specificity were 83.0% and 73.0%, respectively. Chi square analysis showed a significant correlation between ALT levels and both HCV RNA positivity by polymerase chain reaction (PCR) (P < 0.02), and virus load (P<0.05). Interestingly enough, there was a significant positive correlation between HCV RNA and schistosomal antibody titer as measured by hemaglutination inhibition assay (HAI) (P < 0.05). The data presented in this report indicated an association between NO levels and the development and progression of liver cirrhosis. Furthermore, the findings obtained from this study demonstrated that schistomiasis is an important risk factor involved in enhancement of NO levels and virus replication. The latter may aggravate liver cell injury and hence the development of cirrhosis.
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PMID:Evaluation of nitric oxide (NO) levels in hepatitis C virus (HCV) infection: relationship to schistosomiasis and liver cirrhosis among Egyptian patients. 1251 9

The efficacy of two chelating agents (Tiron and calcium disodium EDTA) in the treatment of beryllium induced blood biochemistry and hepatic histopathological alteration was investigated at different duration in female albino rats. Single administration of beryllium nitrate at a dose of 50 mg/kg (im) showed significant decrease in haemoglobin percentage, blood sugar level, protein contents and activity of alkaline phosphatase. On the contrary significant elevation was found in the activity of transaminases (AST and ALT). Tiron was found to be more effective than CaNa2EDTA in reducing the beryllium induced haematological alterations and histopathological lesions in liver. These findings were further confirmed by AAS thus, in which reduced beryllium body burden was seen in liver and blood with Tiron.
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PMID:Comparative effectiveness of Tiron (4,5-dihydroxy benzene 1,3-disulphonic acid disodium salt) and CaNa2EDTA with time after beryllium poisoning. 1255 11

AIMS: Nitric oxide (NO) has protective effects against ischemia-reperfusion (I/R) injury and plays an important role in ischemic preconditioning. Type 1 plasminogen activator inhibitor (PAI-1) regulates plasminogen activators, which may have cytotoxic effects in I/R injury. I/R injury is reduced by the inhibition of fibrinolytic enzymes. To clarify the mechanism of ischemic preconditioning, PAI-1 induction and NO generation were studied in hepatic ischemic preconditioning. METHODS: Total hepatic ischemia was achieved by Pringle's maneuver. FK409 was used as an NO donor. Plasma alanine aminotransferase (ALT) and hyaluronic acid (HA) were measured to estimate hepatic damage and serum nitrite (NO(2)(-)) and nitrate (NO(3)(-)) were also determined to assess NO generation. Reserve transcription-polymerase chain reaction (RT-PCR) and in situ hybridization were carried out to determine the quantitative changes in the expression of PAI-1 mRNA. Plasma PAI-1 concentration was determined using an enzyme-linked immunosorbent assay (ELISA) system. RESULTS: No increase in ALT or HA was found with 5 min I/R. NO and PAI-1 in plasma and PAI-1 mRNA in liver were not increased in the ischemic period, but were increased during the reperfusion period. Infusion of FK409 stimulated induction of PAI-1 mRNA dose dependently. In situ hybridization studies indicated that hepatocytes expressed PAI-1 mRNA after I/R treatment. CONCLUSIONS: I/R increased the concentration of plasma PAI-1. Reperfusion following ischemia was needed for the induction of PAI-1 mRNA and increase of plasma NO concentration. FK409 stimulated PAI-1 mRNA induction in the liver. These results indicate that PAI-1 is a component of the ischemic preconditioning mechanisms, which is stimulated by NO generation.
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PMID:Expression of type 1 plasminogen activator inhibitor and nitric oxide generation in ischemic preconditioning of rat liver. 1269 56

A variety of hepatobiliary abnormalities occur in inflammatory bowel diseases (IBDs). The role of tight junction (TJ) in hepatobiliary complications have been well described. The purpose of this study was to investigate the role of inducible nitric oxide (NOS) in alteration of hepatocyte TJ paracellular barrier and in the rapid transcytotic vesicular pathway modification associated with intestinal inflammation. To address this question, we used an experimental model of colitis, induced by dinitrobenzene sulfonic acid (DNBS). When compared to DNBS-treated iNOS wild-type (WT) mice, DNBS-treated iNOS knock out mice (iNOSKO) mice experienced a significant less rate of the extent and severity of the histological signs of colon injury. Colon levels of the pro-inflammatory cytokines tumour necrosis factor, interleukin-1beta and interleukin-6 were also significantly reduced in iNOS-KO mice in comparison to wild-type mice. Liver histology from iNOSKO and wild-type mice iNOSWT did not show any parenchymal and portal tract inflammation at 4 days after DNBS administration. Serum total bilirubin and alanine aminotransferase, were significantly reduced in DNBS-iNOSKO mice vs DNBS-iNOSKO mice. Therefore, we found an increase of tight junctional permeability to lanthanum nitrate (molecular weight, 433) in the livers from DNBS-treated IL-10WT mice, lanthanum accumulated throughout the junctional area up to the most apical region bordering the lumen. Absence of a functional iNOS gene in iNOSKO mice resulted in a significant reduction of apical diffusion of lanthanum after DNBS-induced colitis. Immunofluorescent labeling of frozen liver sections from DNBS-iNOSWT mice showed a significant alteration of the immunolocalization for claudin-1 and zonula occludens (ZO)-1. In contrast, a significant reduced alteration in the localization of the immunosignals for claudin-1 and ZO-1 was observed in the liver from iNOSKO mice after DNBS administration. In conclusion, we suggest that the iNOS may represent an important pathophysiological mechanism of hepatobiliary injuries and cholestasis observed in patients with IBD.
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PMID:Role of iNOS in hepatocyte tight junction alteration in mouse model of experimental colitis. 1283 36

Overdose of acetaminophen, a widely used analgesic drug, can result in severe hepatotoxicity and is often fatal. This study was undertaken to examine the effects of arabic gum (AG), which is commonly used in processed foods, on acetaminophen-induced hepatotoxicity in mice. Mice were given arabic gum orally (100 g l(-1)) 5 days before a hepatotoxic dose of acetaminophen (500 mg kg(-1)) intraperitoneally. Arabic gum administration dramatically reduced acetaminophen-induced hepatotoxicity as evidenced by reduced serum alanine (ALT) and aspartate aminotransferase (AST) activities. Acetaminophen-induced hepatic lipid peroxidation was reduced significantly by arabic gum pretreatment. The protection offered by arabic gum does not appear to be caused by a decrease in the formation of toxic acetaminophen metabolites, which consumes glutathione, because arabic gum did not alter acetaminophen-induced hepatic glutathione depletion. Acetaminophen increased nitric oxide synthesis as measured by serum nitrate plus nitrite at 4 and 6 h after administration and arabic gum pretreatment significantly reduced their formation. In conclusion, arabic gum is effective in protecting mice against acetaminophen-induced hepatotoxicity. This protection may involve the reduction of oxidative stress.
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PMID:Protective effect of arabic gum against acetaminophen-induced hepatotoxicity in mice. 1452 29


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