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)

1. When aminoguanidine, a nucleophilic hydrazine compound, was administered to rats (50 mg kg(-1) body wt) 30 min before a necrogenic dose of thioacetamide (500 mg kg(-1) body wt), significant changes related to liver injury and hepatocellular regeneration were observed. 2. The extent of necrosis was noticeably less pronounced, as detected by the peak of serum aspartate aminotransferase activity. Depletion of hepatic glutathione (GSH) and the increase in malondialdehyde concentration as markers of oxidative stress, produced by thioacetamide metabolism, were significantly diminished. However, the activity of microsomal FAD monooxygenase, the system responsible for thioacetamide oxidation, did not show significant alterations. Antioxidant enzyme systems involved in the glutathione redox cycle, such as glutathione reductase and glutathione peroxidase activities, slightly decreased following aminoguanidine pretreatment. 3. Primary cultures of peritoneal macrophages from control rats, when incubated in the presence of serum collected following thioacetamide intoxication, showed a significant decrease in nitric oxide (NO) release at 24 h, that was more pronounced in the group pretreated with aminoguanidine. However, the sharp and progressive increase in macrophage NO release, when incubated in the presence of serum obtained at 48, 72 and 96 h, were increased by aminoguanidine-pretreatment. 4. The cell population involved in DNA synthesis sharply increased in both groups at 48 h of intoxication, although the values at 0, 24, 72 and 96 h were markedly higher in the group pre-treated with aminoguanidine. Polyploidy at 72 and 96 h of intoxication was delayed by the effect of aminoguanidine and a progressive increase in the hypodiploid hepatocyte population, which reached 16% of the total at 96 h, was observed. 5. These results indicate that a single dose of aminoguanidine before thioacetamide administration, markedly diminished the severity of the liver injury by decreasing oxidative stress and lipoperoxidation, but hepatocellular regeneration was apparently unaffected probably due to an enhanced mitogenic activity.
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PMID:Influence of aminoguanidine on parameters of liver injury and regeneration induced in rats by a necrogenic dose of thioacetamide. 977 49

Alcohol and cocaine are abused by the general population as well as by pregnant women. Since alcohol and cocaine are hepatotoxic, pregnant mice were used to study the effect of alcohol and/or cocaine on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and on liver ultrastructure. Also, blood glutathione (GSH) and GSH related enzymes such as glutathione reductase (GSH-Rx) and glutathione peroxidase (GSH-Px) were studied. The mice were treated with 0.6 g/kg ethanol twice daily via gavage and/or 20 mg/kg of cocaine hydrochloride intravenously once daily. The treatment was from day 6 to 15 of gestation and these studies were performed at day 18. Our results indicated a significant increase in AST level after treatment with ethanol alone or in combination with cocaine. The blood GSH levels decreased significantly in all the treated groups compared to the control. The activity of GSH-Px was significantly decreased only in the ethanol and cocaine combination group compared to the control. Histopathological studies indicated that co-administration of ethanol and cocaine lead to a significant potentiation in liver toxicity as indicated by increased fatty infiltration.
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PMID:Effect of alcohol and/or cocaine on blood glutathione and the ultrastructure of the liver of pregnant CF-1 mice. 977 56

The hepato-steatogenic compound ethionine has been used to investigate the correlations between in vivo and in vitro toxicity data. The aim was to find a suitable model of toxicity in hepatocyte suspensions or monolayers in vitro, which could predict the known toxicity of ethionine in vivo and which could be implemented in screening compounds of unknown toxicity. Thus a variety of markers of cytotoxicity, metabolic competence and liver-specific functions were investigated in rat hepatocyte suspensions and monolayers and compared with in vivo data in the rat. The following markers were measured in the appropriate system: (1) Neutral red uptake; 3-(4,5 dimethyl)thiazol-2-yl,-2,5-diphenyl tetrazolium bromide (MTT) reduction; lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) leakage (cytotoxicity). (2) ATP levels, protein synthesis and glutathione (GSH) levels (metabolic competence). (3) Urea and triglyceride synthesis and beta-oxidation (liver specific functions). Ethionine (0-30 mM) did not affect the markers of direct cytotoxicity, except neutral red uptake, which was reduced by 18 and 30 mM ethionine after 20 h in culture. ATP and GSH depletion occurred in hepatocyte suspensions at the highest concentrations of ethionine (20 and 30 mM) after 1 h. In monolayers, GSH levels were reduced after 4 h, but not 20 h. Urea synthesis was increased in hepatocyte suspensions from 1 to 3 h by 10-30 mM ethionine and reduced after 20 h in cultured hepatocytes (18-30 mM). Protein synthesis was reduced and beta-oxidation was increased in ethionine-treated hepatocyte suspensions. Unfortunately, there was no measurable effect on triglyceride accumulation within cells (the major biochemical change in vivo) in either system. Ethionine treated hepatocytes in suspension showed the same rate of triglyceride synthesis and transportation out of cells as control cells. Thus, hepatocyte suspensions were able to mimic the early biochemical effects of ethionine in vivo (ATP and GSH depletion, inhibition of protein synthesis) and some effects on urea synthesis, but monolayer cultures appeared to be less sensitive to the toxicity of ethionine. However, neither in vitro system was able to model the effects of ethionine on the accumulation of triglycerides in vivo.
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PMID:Ethionine toxicity in vitro: the correlation of data from rat hepatocyte suspensions and monolayers with in vivo observations. 980 31

The plasma levels of lipoperoxides, glutathione peroxidase (GSH-Px), reduced glutathione (GSH), beta carotene, vitamin A, E, some plasma biochemical and blood haematological parameters were investigated in 40 women with habitual abortion (HA) and controls. The levels of GSH, vitamin A, E and beta carotene were significantly lower in women with HA than in controls. However, the plasma levels of lipid peroxidation, alkaline phosphatase (ALP), glucose and blood haemoglobin were significantly higher in HA than in controls. In addition, plasma levels of GSH-Px, AST, ALT, total bilirubin, total protein, albumin, sodium, potassium, calcium and number of white blood cells, red blood cells, platelet and values of packet cell volume showed no significant differences between HA and controls. According to the results of this study, we observed that the levels of lipid peroxidation were increased and plasma levels of vitamin A, E and beta carotene were decreased in HA. The decrease of those antioxidants may play a significant role in women with habitual abortion.
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PMID:Blood plasma levels of lipoperoxides, glutathione peroxidase, beta carotene, vitamin A and E in women with habitual abortion. 985 84

The hepatoprotective effect of DA-9601, a quality-controlled extract of Artemisia asiatica, on liver damage induced by acetaminophen (APAP) and carbon tetrachloride (CCl4) was investigated by means of serum-biochemical, hepatic-biochemical, and histopathological examinations. Doses of DA-9601 (10, 30, or 100 mg/kg) were administered intragastrically to each rat on three consecutive days i.e. 48 h, 24 h and 2 h before a single administration of APAP (640 mg/kg, i.p.) or CCl4 (2 ml/kg, p.o.). Four h and 24 h after hepatotoxin treatment, the animals were sacrificed for evaluation of liver damage. Pretreatment of DA-9601 reduced the elevation of serum ALT, AST, LDH and histopathological changes such as centrilobular necrosis, vacuolar degeneration and inflammatory cell infiltration dose-dependently. DA-9601 also prevented APAP- and CCl4-induced hepatic glutathione (GSH) depletion and CCl4-induced increase of hepatic malondialdehyde (MDA), a parameter of lipid peroxidation, in a dose-dependent manner. These findings suggest that pretreatment with DA-9601 may reduce chemically induced liver injury by complex mechanisms which involve prevention of lipid peroxidation and preservation of hepatic GSH.
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PMID:Studies on protective effect of DA-9601, Artemisia asiatica extract, on acetaminophen- and CCl4-induced liver damage in rats. 987 86

Antioxidant action of various molds, which are traditionally used for the production of foods or alcoholic beverages in Japan, was studied in vitro and in vivo. Antioxidant action was evaluated by scavenging stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and lipid peroxidation of rat liver microsomes. Among 40 molds, 16 species showed the DPPH scavenging action, and the molds that can scavenge the DPPH radical inhibited lipid peroxidation. The mold with the strongest action, Monascus anka, was chosen for the investigation of a protective action against liver injury of rats. When galactosamine (GalN, 400 mg/kg) or GalN plus lipopolysaccharide (LPS, 0.5 microg/kg) was given intraperitoneally to rats (Sprague-Dawley), aspartate aminotransferase (AST) and glutathione (GSH) S-transferase (GST) activities in serum were significantly increased. However, such hepatotoxicities seen in the increase in serum enzyme levels were depressed when the extract prepared from M. anka was given 1 and 15 h before the toxic insultant. Liver microsomal GST activity, which is known to be activated by oxidative stress, was increased by GalN or GaIN plus LPS treatment and the increase was also inhibited by pretreatment with the extract. Pathomorphological changes in the liver caused by GalN treatment also were prevented by the mold extract. These results indicate that the extract of M. anka has radical scavenging action and ameliorates chemically induced hepatotoxicity.
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PMID:Screening of antioxidant action of various molds and protection of Monascus anka against experimentally induced liver injuries of rats. 1018 24

The purpose of our study was to assess the effects of experimental dicroceliosis on the antioxidant defense capability of the liver in hamsters. Studies were carried out at 80 and 120 days after infection with an oral dose of 40 metacercariae of Dicrocoelium dendriticum. The parasitic pathology was ascertained by the presence of fluke eggs in feces, increased serum ALT and AST activities, and histological findings. The concentration of thiobarbituric acid-reactive substances (TBARS) and the ratio of oxidized to reduced glutathione (GSSG/GSH), measured as markers of oxidative stress, were significantly increased [TBARS: +40% and +84% at 80 and 120 days postinfection (p.i.), respectively; GSSG/GSH: +200% and +117%]. Dicroceliosis increased Se-dependent glutathione peroxidase (GPx) activity in both cytosol (+24% and +46%) and mitochondria (+73% and +41%). Superoxide dismutase activity was significantly reduced in cytosol (-19% and -38%) and mitochondria (-20% and -39%). No significant change was found in the activity of Se-independent GPx or catalase. The ratio of glutathione peroxidase/glutathione reductase at 80 and 120 days p.i. was increased by 25% and 63%, respectively. Gamma-glutamyl cysteinyl synthetase activity was increased by 27% and 20%, respectively. Our data indicate that although dicroceliosis courses with activation of antioxidant enzymes and glutathione synthesis, inefficient scavenging of reactive oxygen species takes place, resulting in oxidative liver damage.
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PMID:Oxidative stress and changes in liver antioxidant enzymes induced by experimental dicroceliosis in hamsters. 1034 40

The effect of prolonged treatment with the standardized Panax ginseng extract G115 on the antioxidant capacity of the liver was investigated. For this purpose, rats that had received G115 orally at different doses for 3 months and untreated control rats were subjected to exhaustive exercise on a treadmill. A bell-shaped dose response on running time was obtained. The results showed that the administration of G115 significantly increases the hepatic glutathione peroxidase activity (GPX) and the reduced glutathione (GSH) levels in the liver, with a dose-dependent reduction of the thiobarbituric acid reactant substances (TBARS). After the exercise, there is reduced hepatic lipid peroxidation, as evidenced by the TBARS levels in both the controls and the treated animals. The GPX (glutathione peroxidase) and SOD (superoxide dismutase) activity are also significantly increased in the groups receiving G115, compared with the controls. The hepatic transaminase levels, ALT (Alanine-amino-transferase) and AST (Aspartate-amino-transferase), in the recuperation phase 48 h after the exercise, indicate a clear hepatoprotective effect related to the administration of the standardized Panax ginseng extract G115. At hepatic level, G115 increases the antioxidant capacity, with a marked reduction of the effects of the oxidative stress induced by the exhaustive exercise.
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PMID:Effects of administration of the standardized Panax ginseng extract G115 on hepatic antioxidant function after exhaustive exercise. 1044 26

N-acetylcysteine (NAC) is a glutathione precursor used to treat several clinical conditions where intracellular oxidant-antioxidant balance is disturbed, among which, acetaminophen induced hepatotoxicity may be counted. In this study, administering thioacetamide (TAA) as a hepatotoxic agent, a rat model of hepatotoxicity has been established, to investigate some of the immune mediated basic oxidant-antioxidant homeostatic mechanisms involved, and potential serum markers for follow-up of disease and treatment. To do this, four experimental groups receiving saline/saline, saline/NAC, saline/TAA and NAC/TAA as intraperitoneal injections, have been formed. Rat serum tumor necrosis factor-alpha (TNF-alpha), Interleukin1-beta (IL1-beta), malondialdehyde (MDA) as a measure of final oxidant damage and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) have been assayed. Hepatocellular damage has been measured via the biochemical estimates ALT, AST and LDH as well as histopathological grading. It was found that both TNF-alpha and IL1-beta were significantly elevated in saline/TAA receivers (P<0.01) when compared to NAC/TAA receivers. Serum MDA was also increased in TAA receivers in addition to SOD (P<0.05) and GSH-Px (P<0.05). Serum nitrite levels have also been assayed to give an estimate of nitric oxide that is suggested as a counter-balancer of oxidant stress. NAC/saline receivers had the highest levels of nitrites in the serum (P<0.05). Our results indicate that part of the hepatocellular injury to rat liver, induced by TAA is mediated by oxidative stress caused by the action of cytokines imparted by the enzymatic SOD and GSH-Px and non-enzymatic gaseous nitric oxide mechanisms causing an alleviation on administration of NAC. In addition, TNF-alpha, IL1-beta, MDA, SOD, GSH-Px and nitrites are potential candidates of serum indicators for monitorization of pathophysiological stage of liver disease.
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PMID:Serum cytotoxin and oxidant stress markers in N-acetylcysteine treated thioacetamide hepatotoxicity of rats. 1060 91

Nickel, a major environmental pollutant is known for its clastogenic, toxic and carcinogenic potentials. The present investigation shows that ellagic acid proves to be exceptional in the amelioration of the nickel-induced biochemical alterations in serum, liver and kidney. Administration of nickel (250 micromol Ni/kg body wt) to female Wistar rats, resulted in increase in the reduced glutathione (GSH) content [kidney (*P<0.05) and liver (**P<0.001)] and Glutathione-S-transferase (GST) and glutathione reductase (GR) activities [kidney and liver, (**P<0.001)]. Ellagic acid treatment to the intoxicated rats leads to the formation of soluble ellagic acid-metal complex which facilitates excretion of nickel from the cell or tissue, thus ameliorating nickel-induced toxicity, as evident from the down regulation of GSH content, GST and GR activities with concomitant restoration of glutathione peroxidase (GPx) activity in liver and kidney. Our data shows that ellagic acid maintains cell membrane integrity through sequestration of metal ions from the extracellular fluid, as evident from the alleviated levels of serum glutamate oxaloacetate transaminase, (SGOT), serum glutamate pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH) when compared to nickel treated group. Similarly, the enhanced blood urea nitrogen (BUN) and serum creatinine levels that are indicative of renal injury showed a reduction of about 45 and 40%, respectively. The data also show that treatment of ellagic acid after 30 min of nickel administration exhibits maximum inhibition in a dose-dependent manner. In summary, our data suggests that ellagic acid act as an effective chelating agent in suppressing nickel-induced renal and hepatic biochemical alterations.
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PMID:Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress. 1060 94


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