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)

HPLC analysis revealed that luteoskyrin administered orally to male mice accumulated selectively in the liver, with minor distribution to the serum and kidneys. Elevation of serum GOT and GPT values was maximal 3 days after administration. In mice administered this mycotoxin intravenously, selective accumulation was also observed in the liver, and the half-life of hepatic luteoskyrin in males was significantly longer than that in females. Increment of serum transaminases was also marked in males with maximum accumulation at 24 h after administration. Histopathologically, cellular membrane damage was an early effect of luteoskyrin on cell necrosis, and these morphological changes were also marked in males. Luteoskyrin also elevated hepatic lipid peroxides, the maximum elevation being 8 h after injection; this increase was suppressed by alpha-tocopherol and Bi(NO3)3. HPLC-ECD analysis indicated that the level of 8-hydroxy-deoxyguanosine, one of the markers of hydroxy-radical-mediated modification of DNA guanine residues, was increased in hepatic DNA. These findings indicate that luteoskyrin has a high affinity for the liver, resulting in induction of lipid peroxidation, hepatocellular membrane damage, and elevation of serum transaminase activities. It is suggested that the hydroxy radicals derived from this anthraquinone contribute to these toxicological changes.
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PMID:Hepatic accumulation and hepatotoxicity of luteoskyrin in mice. 160 44

Aluminium (Al) chloride (10-200 microM) increased the Al content in hepatocytes isolated from fed male rats in a time- and concentration-dependent manner. After 60 min of incubation with 100 microM Al about 45% of cellular Al was found each in the mitochondrial and the postmitochondrial fraction of hepatocytes, whereas about 5% of Al sedimented with nuclei and cell debris. Concomitantly, the leakage of lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the presence of Al time- and concentration-dependently, but only to a moderate extent. Aluminium (10-200 microM) also accelerated the formation of lactate by hepatocytes. No significant differences were found in Al uptake and distribution and its effect on LDH leakage and lactate formation when the metal ion was given as AlCl3, Al(NO3)3 or Al(lactate)3. Al concentrations (AlCl3) exceeding 250 microM severely disturbed the determination of LDH, AST and lactate in a cell free system. The data suggest only a moderate toxicity of Al compounds to isolated hepatocytes, when given in amounts approximating (patho)physiological conditions.
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PMID:Uptake and distribution of aluminium in rat hepatocytes and its effect on enzyme leakage and lactate formation. 356 54

The relationship between reticuloendothelial system (RES) function and acute phalloidin intoxication was studied in mice. Pretreatment with compounds that stimulate (zymosan) or depress (methyl palmitate and praseodymium nitrate, Pr(NO3)3) the RES resulted in protection against phalloidin-induced lethality and hepatotoxicity, as assessed by morphological analysis. However, triolein (which stimulates the RES) was ineffective against phalloidin. The timing of pretreatment with the effective compounds showed a correlation between modified in vivo RES function (phagocytosis) and protection against the toxin. The effects of pretreatment with zymosan and Pr(NO3)3 were further characterized. Hepatic damage induced by phalloidin was significantly decreased by these agents, as judged by morphological analysis as well as by serum aspartate aminotransferase and alanine aminotransferase release. This study also showed that there was no correlation between the capacity of Kupffer cells to produce nitrite and prophylaxis against phalloidin. However, liver cell proliferation was increased by zymosan and Pr(NO3)3 in parallel with protection against the toxin. Furthermore, freshly isolated hepatocytes from zymosan- or Pr(NO3)3-treated mice were less sensitive to phalloidin in vitro. These results indicate that the protective effect of these agents against phalloidin-induced hepatotoxicity may be mediated by their mitogenic properties.
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PMID:Effect of agents which modify reticuloendothelial system function on acute phalloidin-induced lethality and hepatotoxicity in mice. 856 Apr 77

The aim of this work was to determine if the inhibition or stimulation of NO synthesis modulates liver damage induced by the chronic administration of CCl4. CCl4 was administered three times a week for 8 weeks to male Wistar rats treated simultaneously with N omega-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg, p.o., twice a day), aminoguanidine (AG, 4 g/L in the drinking water), or L-arginine (500 mg/kg, p.o., twice a day); appropriate controls were performed. Serum NO2- + NO3- increased in the groups treated with CCl4 and/or L-arginine, but the effect was prevented by either L-NAME or AG. In the liver, lipid peroxidation and collagen content increased, while glycogen content decreased in the CCl4-treated group (P < 0.05); L-NAME and AG accentuated these effects. Serum enzyme activities of alanine aminotransferase (ALT), alkaline phosphatase, and gamma-glutamyl transpeptidase (gamma-GTP) and bilirubin content increased about 2-, 3-, 2-, and 6-fold, respectively, after CCl4 intoxication (P < 0.05); L-NAME or AG cotreatment further increased the enzyme activities (P < 0.05). L-Arginine treatment protected the liver partially from the elevation of collagen, bilirubins, and alkaline phosphatase and from glycogen depletion induced by CCl4 intoxication (P < 0.05), but showed no significant effect on ALT, gamma-GTP, or lipid peroxidation. These results suggest that NO protects the liver against oxidative injury, because NO inhibition by L-NAME or AG increased lipid peroxidation and the other markers of liver injury studied herein.
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PMID:Nitric oxide protection of rat liver from lipid peroxidation, collagen accumulation, and liver damage induced by carbon tetrachloride. 975 Oct 83

It is well revealed that activation of macrophages stimulated by endotoxin resulted in induction of nitric oxide synthase which catalyze nitric oxide (NO) formation from L-arginine. Consequently, blood concentrations of NO2-/NO3- (NOx-) are shown to increase. We studied on pharmaco/toxicokinetics of NOx- in serum and principal organs in Wistar male rats after i.p. administrations of LPS and NaNO3. The serum levels of NOx- at 1 h and 6 h after nitrate administration (10 mg/kg, i.p.) were 240 and 120 microM, respectively. Tissue levels of NOx- in lung, liver and kidneys were ca.1/2 of the serum level. Those levels in spleen and brain were ca.1/4 and 1/10 of the serum level, respectively. The correlation of NOx- levels in serum and these 5 organ tissues between 1 h and 6 h after administration of nitrate was r = 0.992 suggesting no specific accumulation of NOx- in these organs. The serum level of NOx- at 18 h after LPS treatment (1 mg/kg, i.p.) was 430 microM. The correlation of NOx- levels in serum and 5 organ tissues between LPS and nitrate administrations was shown to be r = 0.851. NOx- levels of serum, lung, kidneys and brain showed good correlation but liver and spleen showed out of the correlation. The liver tissue level of NOx- after LPS treatment was low compared with the expected value from the serum level. The reason may be explained partially by the liver weight increase and the liver toxicity with increased GPT and gamma-GT levels due to LPS. Contrary to this, NOx- level of spleen tissue after LPS treatment was more than 2-fold compared with the expected value from the serum level suggesting NO formation in the spleen. This was supported by the markedly high concentration (73.2 nmol/g tissue) of NO2- in the spleen tissue. NO2- levels in lung (34.5 nmol/g tissue) and brain (14.3) were also found to be significantly high after stimulation with LPS suggesting NO formation in these organs. Increased formation of NO2- in these organs by LPS stimulation suggests the formation of active nitrogen oxides such as N2O3 which is an effective nitrosating agent in non-acidic conditions in vivo.
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PMID:[NO2-/NO3- levels in blood and principal organs in rats treated with lipopolysaccharide]. 1009 17

The levels of plasma nitric oxide (NO), endothelin-1 (ET-1) and ALT in the patients with chronic hepatitis B and active cirrhosis and the correlation among them were observed and analyzed. NO3- was restored by using cadmium column assay and NO2- measured by heavy nitrogen assay. The primitive NO3- and total restored NO2- (NO3-/NO2-) in plasma of the patients with chronic hepatitis and cirrhosis. Plasma ET-1 and ALT levels were determined by using radioimmunological assay and Lai's assay, respectively. Compared with normal control group, the plasma levels of NO2-/NO2- and ET-1 in the patients with chronic active hepatitis and active cirrhosis were significantly increased (P < 0.05-0.01). There was a positive correlation between NO and ALT, and ET-1 and ALT in the patients with chronic active hepatitis and active cirrhosis respectively. It was suggested that elevation of both NO and ET-1 levels were closely related with injury severity of liver function.
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PMID:Study on the correlation of plasma NO, ET-1 and ALT in the patients with chronic hepatitis and cirrhosis. 1121 47

We recently reported that nitrotyrosine and acetaminophen (APAP)-cysteine protein adducts colocalize in the hepatic centrilobular cells following a toxic dose of APAP to mice. Whereas APAP-adducts are formed by reaction of the metabolite N-acetyl-p-benzoquinone imine with cysteine, nitrotyrosine residues are formed by reaction of tyrosine with peroxynitrite. Peroxynitrite is formed from nitric oxide (NO) and superoxide. This manuscript examines APAP (300 mg/kg) hepatotoxicity in mice lacking inducible nitric oxide synthase activity (NOS2 null or knockout mice; C57BL/6-Nos2(tm1Lau)) and in the wildtype mice. In a time course the ALT levels in the exposed NOS2 null mice were approximately 50% of the wildtype mice; however, histological examination of liver sections indicated similar levels of centrilobular hepatic necrosis in both wild-type and NOS2 null mice. Serum nitrate plus nitrite levels (NO synthesis) were identical in saline-treated NOS2 null and wild-type mice (53 +/- 2 microM). APAP increased NO synthesis in wild-type mice only. The increases paralleled the increases in ALT levels with peak levels of serum nitrate plus nitrite at 6 h (168 +/- 27 microM). In wild-type mice hepatic tyrosine nitration was greatly increased relative to saline treated controls. Tyrosine nitration increased in NOS2 null mice also, but the increase was much less. APAP increased hepatic malonaldehyde levels (lipid peroxidation) in NOS2 null mice only. The results suggest the presence of multiple pathways to APAP-mediated hepatic necrosis, one via nitrotyrosine, as in the wild-type mice, and another that is not dependent upon inducible nitric oxide synthase activity, but which may involve increased superoxide.
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PMID:Acetaminophen-induced hepatotoxicity in mice lacking inducible nitric oxide synthase activity. 1158 58

Overproduction of nitric oxide (NO) in the liver has been implicated as an important event in endotoxin shock and in other models of hepatic inflammation and injury. The present study was undertaken to evaluate the effect of ONO-1714, a potent and specific inhibitor of inducible NO synthase (iNOS), on acetaminophen-induced hepatotoxicity in the rats. Oral administration of ONO-1714 dose-dependently inhibited NOx (NO2- and NO3-) accumulation in rat plasma after lipopolysaccharide (LPS) treatment. Intraperitoneal acetaminophen at 1 g/kg caused damage to the centrilobular regions of the liver and increase in serum alanine and aspartate transaminase (ALT and AST, respectively) levels accompanied by elevated plasma NOx levels after 24 h. Oral administration of ONO-1714 at 10 and 100 microg/kg dose-dependently reduced the acetaminophen-induced hepatic tissue damage and the increases in serum ALT and AST levels. ONO-1714 also blocked the increase in plasma NOx concentrations. These findings demonstrate that oral ONO-1714, an iNOS inhibitor, protects against acetaminophen-evoked hepatic inflammation/injury, strongly suggesting that NO produced by iNOS plays a key role in the pathogenesis of this drug-induced hepatotoxicity.
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PMID:Effect of a potent iNOS inhibitor (ONO-1714) on acetaminophen-induced hepatotoxicity in the rat. 1465 71

Previous research showed that nano-TiO2 could significantly promote photosynthesis and greatly improve growth of spinach, but we also speculated that an increase of spinach growth by nano-TiO2 treatment might be closely related to the change of nitrogen metabolism. The effects of nanoanatase TiO2 on the nitrogen metabolism of growing spinach were studied by treating them with nano-anatase TiO2. The results showed that nano-anatase TiO2 treatment could obviously increase the activities of nitrate reductase, glutamate dehydrogenase, glutamine synthase, and glutamic-pyruvic transaminase during the growing stage. Nano-anatase TiO2 treatment could also promote spinach to absorb nitrate, accelerate inorganic nitrogen (such as NO3--N and NH4+-N) to be translated into organic nitrogen (such as protein and chlorophyll), and enhance the fresh weight and dry weights.
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PMID:Influences of nano-anatase TiO2 on the nitrogen metabolism of growing spinach. 1675 45

Scutellarin is a natural compound from a Chinese herb. The purpose of this paper was to study the protective effect of scutellarin on concanavalin A (Con A)-induced immunological liver injury and its effect on liver nuclear factor kappaB (NF-kappaB), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and inducible nitric oxide synthase (iNOS) expression in mice. Mouse liver injury was produced by injection of Con A 25 mg kg-1 via the tail vein. Scutellarin 50 or 100 mg kg-1 was peritoneally administered to mice 9 or 1 h before injection of Con A. The levels of serum alanine aminotransferase (ALT) and asparatate aminotransferase (AST), NO2-/NO3- and TNF-alpha were determined with biochemical kits, and ELISA using Quantikine Mouse TNF-alpha kit according the manufacturer's instructions. Liver lesions were examined by light microscope. The expression of TNF-alpha, IFN-gamma, iNOS and Fas mRNA in the livers was detected by RT-PCR; and the expression of c-Fos, c-Jun, iNOS and IkappaB proteins was measured by Western Blotting. As a result, pretreatment with scutellarin 100 mg kg-1 significantly decreased the serum ALT, AST, NO2-/NO3- and TNF-alpha levels, and also reduced liver lesions induced by Con A. Scutellarin 100 mg kg-1 down-regulated expression of TNF-alpha and iNOS mRNA, and c-Fos, c-Jun and iNOS protein, while scutellarin enhanced the degradation of IkappaB in the livers of mice injected with Con A. The results suggest that scutellarin has a protective action against Con A-induced liver injury in mice, and its active mechanism may be related to the inhibition of the NF-kappaB-TNF-alpha-iNOS transduction pathway.
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PMID:The protective action of scutellarin against immunological liver injury induced by concanavalin A and its effect on pro-inflammatory cytokines in mice. 1722 28


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