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)

Since it is known that the metabolism of acetaminophen is involved in its hepatotoxicity and that drug metabolizing enzyme activity is decreased in tumor bearing animals, it was of interest to study the influence of L-1210 leukaemia on acetaminophen hepatotoxicity in BDF-1 male mice. A single oral dose of acetaminophen, 125 mg/kg, was given at the fifth day of the mice survival period (7.7 days) and the animals killed twenty-four hours later. As revealed by serum glutamic-pyruvic transaminase, serum glutamic-oxaloacetic transaminase and lactic dehydrogenase, acetaminophen was less hepatotoxic in leukaemic mice than in control mice by comparison with their own saline group; on the other hand the difference between control and leukaemic mice treated with acetaminophen was significant only for glutamic-pyruvic transaminase. Moreover, we found higher unchanged acetaminophen concentrations in plasma, liver, kidneys, brain and fat of the leukaemic mice as compared to controls, less conjugated metabolites in plasma and liver, decreased in vitro aniline hydroxylation and ethylmorphine N-demethylation. Finally, following acetaminophen administration, reduced hepatic glutathione was depleted to a much lesser extent in the tumor bearing animals than in controls. In conclusion, the L-1210 leukaemia seems to modify the acetaminophen hepatotoxicity and this effect might be explained by decreased acetaminophen biotransformation into toxic metabolites or intermediates.
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PMID:Influence of leukaemia on acetaminophen-induced hepatotoxicity in mice. 689 Feb 27

The effect of oral administration of praziquantel at different dose levels on the activities of metabolizing hepatic enzymes (aminopyrine N-demethylase, aniline 4-hydroxylase and UDP-glucuronyltransferase) was studied in healthy locally bred rabbits. The pathological changes resulting from drug's toxicity were assessed histologically, by measurement of total plasma protein concentration and of the activities of the plasma enzymes sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST). No significant changes were obtained after praziquantel administration at dose levels of 40 and 800 mg/kg body weight, whereas 1600 mg/kg and 2000 mg/kg of praziquantel resulted in a significant decrease in the activities of the three drug-metabolizing hepatic enzymes under investigation in the livers of treated rabbits. All rabbits which received praziquantel at the dose rate of 2000 mg/kg died 10-20 hours following praziquantel treatment.
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PMID:The effect of praziquantel on the activities of some drug-metabolizing hepatic enzymes in rabbits. 760 Sep 44

The purpose of this study was to investigate the role of hydrolysis products of linoleic acid anilide (LAA), i.e., aniline and linoleic acid (LA), in the toxicity to the hemopoietic system, especially to the spleen. To achieve this, the parent compound (LAA) and its putative hydrolysis products, i.e., aniline or linoleic acid (LA), were given to male SD rats at equimolar doses (0.7 mmol/kg) in 0.25 ml mineral oil by gavage, daily, for 14 days. The controls received equal volumes of vehicle only. Five animals from each group were euthanized at Days 1, 7, and 28 following the last dose. At all time points, spleen weights increased in the LAA- and aniline-treated rats, but spleen to body weight ratios were increased only at Days 1 and 7 in these groups. No changes were observed in the LA-treated rats at any time point. RBC counts were decreased in the LAA and aniline groups at Days 1 and 7, whereas hemoglobin content was decreased by 20 and 13% in the LAA- and aniline-treated rats, respectively, only at Day 1. Methemoglobin content in the LAA and aniline groups also increased by 76 and 101%, respectively, at Day 1. Serum transaminases (AST and ALT) decreased in the LAA, aniline, and LA groups but the decreases were more consistent in the LA group. Serum IgA increased in the LAA and aniline groups only at Day 1. Splenic iron content was increased 381, 486, and 51% in the LAA-treated rats and 474, 491, and 58% in the aniline-treated rats at Days 1, 7, and 28, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematopoietic toxicity of linoleic acid anilide: importance of aniline. 766 6

Male Sprague-Dawley rats maintained on either normal diet (N) or on a diet containing phenobarbital (PB; 225 ppm) or mirex (M; 10 ppm) for 15 days received either corn oil or 1 single administration of a protective dose of CCl4 (0.3 ml/kg, po) on day 16. At 24, 48, 72, 96, or 144 hr after the protective dose, a high dose of CCl4 (5 ml/kg, po) was administered to rats of all the groups, and they were observed for 14-day lethality. In a second experiment, in rats maintained on N, PB, or M diet, liver microsomal cytochromes P-450, aminopyrine demethylase, and aniline hydroxylase were measured at various time points after the administration of the protective dose of CCl4. Serum aspartate transaminase, alanine transaminase, and sorbitol dehydrogenase elevations and histopathological changes observed under a light microscope were used as toxic end points to assess hepatotoxicity. Autoprotection was 100% when the high dose was given at 24 hr after the protective dose in N rats, whereas it was only 55% in PB- or M-pretreated rats. For later time points of 48, 72, and 96 hr, autoprotection was only around 50% in N rats, whereas it was almost 100% in PB- and M-pretreated rats. When the high dose was administered at 144 hr after the protective dose, autoprotection further declined to 25% in N rats and to 75% in M-treated rats, but it remained at 100% in PB-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of phenobarbital and mirex pretreatments on CCl4 autoprotection. 781 19

The effects of anabolic-androgenic steroid administration and exercise training on various aspects of hepatic function were investigated in sedentary and trained (treadmill for 12 wk) male and female rats treated orally with fluoxymesterone or methylandrostanolone (2 mg.kg-1 body weight, 5 d.wk-1 for 8 wk). The mean values of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, and total- and high-density lipoprotein-cholesterol remained within normal range in all groups of male animals. The same is true for female rats, except for an increase in alkaline phosphatase activity in the steroid-treated groups. Hepatic microsomal aniline p-hydroxylase activity was reduced in male and increased in female rats by either steroid, whereas no significant effect was detected on 7-ethoxycoumarin deethylase activity. The levels of cytochrome P-450 and cytochrome b5 were markedly decreased by the anabolic-androgenic steroid treatment in male rat microsomes, but neither the steroid administration nor exercise training induced significant changes in the cytochrome levels of female rat livers. Taking into account the significant increase in microsomal protein yield elicited by fluoxymesterone or methylandrostanolone treatment both in males and females, it is noteworthy that the total monooxygenase activities and cytochrome P-450 content, expressed on a per gram liver basis, were significantly increased in female whereas they were apparently unchanged in male rats. In conclusion, the present data show that the prolonged ingestion of high doses of anabolic-androgenic steroids, either with or without concurrent exercise training, can modify in a sex-dependent manner the capacity of rat liver to metabolize drugs without affecting classical serum indicators of hepatic function.
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PMID:Effect of training and anabolic-androgenic steroids on drug metabolism in rat liver. 835 Jul 4

Rifampicin conferred significant protection against carbon tetrachloride (CCl4)-induced liver injury. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were not markedly altered and only hepatocellular fatty degeneration was found in mice pretreated with rifampicin (200 mg/kg), whereas severe centrilobular necrosis was observed and serum ALT and AST activities were as high as 281 and 271 I.U./l, respectively, in the control group following administration of CCl4 (400 microliters/kg). The contents and activities of microsomal drug-metabolizing enzymes in rifampicin-pretreated animals were also much higher than those of the controls. CCl4-mediated malondialdehyde (MDA) formation was increased in rifampicin-treated liver microsomes, demonstrating that rifampicin was capable of increasing the NADPH-dependent metabolism of CCl4 catalyzed by P-450 2E1 to produce free radicals. However, MDA formation was obviously depressed by rifampicin at varying concentrations from 2 to 32 x 10(-6) M in an in vitro cytochrome P-450 (P-450) enzyme system. On the other hand, NADPH oxidation in the metabolism of CCl4 and aniline hydroxylation were not suppressed in the presence of rifampicin in this systems, suggesting that rifampicin did not influence the biotransformation of CCl4 by P-450 2E1 in vitro. Therefore, the protective effect of rifampicin against CCl4 hepatotoxicity appeared to result from the direct inhibition of lipid peroxidation generated by CCl4-derived free radicals.
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PMID:Protective effect of rifampicin against acute liver injury induced by carbon tetrachloride in mice. 878 35

The purpose of this investigation was to determine the effects of experimental dicrocoeliosis on the hepatic oxidative drug-metabolizing system in hamsters. Studies were carried out 80 and 120 days after infestation with an oral dose of 40 metacercariae of Dicrocoelium dendriticum. The parasitic pathology was ascertained by detection of the fluke eggs in faeces, increased serum alanine aminotransferase and aspartate aminotransferase activities, and postmortem and histological findings. Cytochrome P-450 concentration, aniline hydroxylase activity and ethoxycoumarin O-deethylase activity were significantly decreased in both groups of infected animals. Aminopyrine N-demethylase activity and erythromycin N-demethylase activity were only reduced 120 days after infection. Effects on drug metabolizing enzymes were unrelated to changes in the physical state of the microsomal membrane, as assessed by measurement of fluorescence polarization. The results of this study indicate that the capacity of the liver for handling drugs and xenobiotics may be impaired as a consequence of dicrocoeliosis.
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PMID:Effects of experimental dicrocoeliosis on oxidative drug metabolism in hamster liver. 898 69

During L. donovani infection in golden hamsters, tremendous hepatic damage was observed as apparent from increased activities of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, succinate dehydrogenase, glucose-6-phosphatase and acid ribonuclease. The levels of cytochrome P-450 and related monooxygenases, viz. aniline hydroxylase and aminopyrine-N-demethylase registered significant decrease in infected animals. Sodium stibogluconate, a standard antileishmanial drug, though caused the removal of parasites from infected tissues, but did not help in the recovery of deranged hepatic markers. The results explain the higher mortality of stibanate treated infected animals as compared to untreated animals infected with L. donovani.
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PMID:Effect of sodium stibogluconate on hepatic mixed function oxidase system and marker enzymes of golden hamsters during Leishmania donovani infection. 931 42

The present study reports on the effects of horminone on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, on hepatic cytochrome P450 (P450) and cytochrome b5 (cyt b5) contents and on the activities of NADPH-cytochrome P450 reductase (NR), mixed function mono-oxygenases (MFO), glutathione-S-transferase (GST) and glutathione reductase (GR) of Wistar male rat. Horminone is a diterpenoid quinone (7,12-dihydroxyabiet-8,12-diene-11,14-dione) present in several species of the Labiatae family and used as medicinal plants in folk medicine. In this study, horminone was administered by the intraperitoneal route (i.p.) at a concentration of 1 or 10 mg/kg to each group of six mice, using water as a vehicle. On the one hand, results showed that horminone increased serum ALT and AST levels and cyt b5 content and induced the activities of ethylmorphine N-demethylase (EMD). On the other hand, horminone decreased P450 content and inhibited the activities of 7-ethoxyresorufin O-deethylase (ERD), 7-ethoxycoumarin O-deethylase (ECD), aniline 4-hydroxylase (AH) and NR. Based on these results, the possibility of toxic effects occurring after administration of plant extracts containing horminone must be considered.
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PMID:Effects of horminone on liver mixed function mono-oxygenases and glutathione enzyme activities of Wistar rat. 932 1

A cDNA of amine sulfotransferase-RB1 (AST-RB1), which efficiently catalyzes 4-phenyl-1,2,3,6-tetrahydropyridine (PTHP) sulfation, has been isolated by immunoscreening of a rabbit liver cDNA library. The cDNA consisted of 1,117 base pairs and encoded a protein of 301 amino acids with a molecular weight of 35,876. The deduced amino acid sequence matched at six positions those of peptide fragments obtained from purified AST-RB1 protein. The sequence had less than 38% identity at the amino acid level with cytosolic sulfotransferases in mammals, although high degrees of similarity were observed with regions conserved throughout mammalian sulfotransferases. These results indicate that AST-RB1, arbitrarily named sulfotransferase 3A1 (ST3A1), constitutes a new and third gene family of cytosolic sulfotransferases in mammals. ST3A1 expressed in Escherichia coli as a fused protein catalyzed sulfation of amines such as PTHP, aniline, 4-chloroaniline, 2-naphthylamine, and desipramine, but barely O-sulfation of typical aryl and hydroxysteroid sulfotransferase substrates. These data unequivocally demonstrate the existence of a cytosolic sulfotransferase showing a high selectivity for amine substrates, and indicate that multiple forms of sulfotransferase mediate sulfation of xenobiotics in mammalian livers.
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PMID:Molecular cloning and expression of an amine sulfotransferase cDNA: a new gene family of cytosolic sulfotransferases in mammals. 953 31


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