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:1.6.99.3 (diaphorase)
5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the presence of hepatic microsomes, styrene produced a type I difference spectrum, which demonstrates that styrene binds to the catalytic site of ferricytochrome P-450. A comparison of the binding parameters for the interaction of styrene with noninduced, phenobarbital-induced, and 3-methylcholanthrene-induced microsomes indicated that styrene is predominantly bound by cytochrome P-450 and not by cytochrome P-448. Inhalation exposure to a mixture of acetone (1,000 ppm, 6 h/d) and styrene (300 ppm, 6 h/d) for 5 d caused a distinct decrease in hepatic free nonprotein sulfhydryl groups. This decrease could be observed both with and without phenobarbital treatment. Acetone inhalation alone also enhanced ethoxycoumarin O-deethylase activity in rats without pretreatments. Acetone inhalation also increased the cytochrome P-450 content of liver microsomes, but it had no effect on NADPH cytochrome c reductase or epoxide hydratase activity. Combined exposure to styrene and acetone enhanced NADPH cytochrome c reductase activity in nonphenobarbital-treated rats, but no effect was seen in the phenobarbital-treated animals. Phenobarbital treatment of animals can greatly modify the biotransformation and toxicity of styrene, phenobarbital inducible P-450 hemoprotein playing a predominant role in its metabolism. Simultaneous inhalation exposure to acetone also interacts with the metabolism of styrene.
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PMID:Interaction of styrene and acetone with drug biotransformation enzymes in rat liver. 73 16

Adult rats of either sex and mature females ovariectomized 44 days earlier, were partially hepatectomized under ether anesthesia, leading to two-thirds organ removal. The respective controls were incised and the livers manipulated by hand. At specified p.o. periods, hepatic microsomal total protein, cytochrome P-450 and activities of the enzymes, aminopyrine demethylase and benzo[a]pyrene hydroxylase were determined for the respective pairs and submitted to analysis of variance. The data are expressed as ratios of the sham-operated to the partially hepatectomized group mean values on a percentage basis. For one male series, cytochrome P-450 and the 2 enzyme activities were significantly elevated with the intact rats at 72 and 96 h and 10 days and in yet another series of the same sex, the findings were similar except that only the cytochrome level of the controls was increased at day 10; the ratios normalized by day 21. As screened in a few groups, the changes in microsomal NADPH cytochrome c reductase were not noteworthy. Possible latency periods were shorter for the female series and the hydroxylase activity was elevated in the intact liver microsomes over test periods of 24 h to 10 days. In general, although a trend of increased parameter value for the intact group was apparent and in agreement with several published reports, statistical significance could not be substantiated in many instances, wide variations and sporadic data being encountered. None of the intact group changes in the constants were significant with the ovariectomized series. The effect of an inducer, phenobarbital, was determined in relation to the 10 day-ratios derived for males fed a casein based control diet as such and supplemented with 30 wt % each of glucose, fructose, galactose, maltose and lactose, the last one being screened only in partially hepatectomized rats. Phenobarbital was injected i.p. daily at 80 mg/kg on the last 3 days. Among other changes noted with the respective ratios, each of the intact groups displayed remarkable elevations in the total protein content. Additional comparisons are also advanced for the individual group parameter findings in relation to the control diet- and the 30% glucose-fed animals.
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PMID:Variations in microsomal parameters of intact and regenerating rat liver with time and on feeding high carbohydrate diets. 235 31

Female albino mice were fed sublethal doses of KCN (approx. 10 micrograms/mouse/day) for 7 days, injected intraperitoneally with phenobarbitone (50 mg/kg body wt/day) in the subsequent 3 days, and sacrificed 24 hr after the last injection. Phenobarbitone sleeping time was increasingly shortened (16-27%) daily in cyanide-fed mice in comparison with cyanide-free controls. Both compounds administered singly or simultaneously increased the liver weight/body weight ratios by not more than 10%. Aniline hydroxylase, glucose-6-phosphatase, NADPH- and NADH-cytochrome c reductase activities were similarly increased. Aniline hydroxylase activity was most markedly increased (by a factor of 4). The toxicological implications of these results are discussed.
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PMID:Hepatic effects of phenobarbitone in female mice fed sublethal levels of dietary cyanide. 302 73

The effect of phenobarbital (100 mg/kg i.p.) and 6-aminonicotinamide (6AN) (35 mg/kg i.p.) on enzyme activities related to energy transduction was investigated on the homogenate "in toto", non-synaptic mitochondrial fraction and synaptosomal fraction isolated from different rat brain areas (cerebral cortex, hippocampus, hypothalamus, striatum, and medulla oblongata). 6AN treatment decreased: phosphofructokinase in all the areas tested; lactate dehydrogenase on the homogenate "in toto" in striatum and hypothalamus, and on the synaptosomal fraction in cerebral cortex and corpus striatum; succinate dehydrogenase on non-synaptic mitochondrial fraction in hippocampus and striatum. Finally, aspartate aminotransferase was increased on non-synaptic mitochondrial fraction in striatum and medulla oblongata. Phenobarbital treatment induced an increase of total NADH cytochrome c reductase on mitochondrial fraction in hippocampus and hypothalamus, and a decrease of cytochrome oxidase activity on non-synaptic mitochondrial fraction in hypothalamus and medulla oblongata.
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PMID:Phenobarbital and 6-aminonicotinamide effect on cerebral enzymatic activities related to energy metabolism in different rat brain areas. 303 30

The ability of phenobarbital (PB) to neonatally "imprint" or "program" the hepatic microsomal cytochrome P-450-dependent monooxygenase system (MOS) was investigated. Phenobarbital (30 mg/kg) was administered subcutaneously to neonatal rats of both sexes on days 1-5 postpartum. Various hepatic MOS activities were measured at 6, 22, 50 and 140 days of age. Six-day-old animals of both sexes displayed the increased hepatic microsomal protein levels and enzyme activities expected from the action of phenobarbital as a transitory MOS inducer. Most of these increases dissipated by 22 and 50 days of age. However, at 140 days of age rats of both sexes that had received neonatal phenobarbital showed increased levels of cytochrome P-450, as well as both P-450 and cytochrome c reductase, ethoxycoumarin O-deethylation, glucuronyl transferase activity, in vitro covalent binding of benzo[a]pyrene to DNA and in vivo covalent binding of aflatoxin B1 to hepatic macromolecular fractions. Neonatal phenobarbital administration can alter the metabolic profile of rats in adulthood, apparently by a mechanism different from that responsible for either transitory PB induction or testosterone imprinting.
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PMID:Xenobiotic imprinting of the hepatic monooxygenase system. Effects of neonatal phenobarbital administration. 392 Oct 29

Treatment with beta-naphthoflavone (BNF) was found to induce 7-ethoxyresorufin O-deethylase and aryl hydrocarbon hydroxylase activities about 500-fold in the microsomal fraction of the rat ventral prostate but had no effect on aminopyrine N-demethylase or reduced nicotinamide adenine dinucleotide phosphate:cytochrome c reductase activities. Phenobarbital (PB) treatment did not alter any of these enzyme activities. Antibodies raised in rabbits against rat liver cytochrome P-450 reductase (P-450 reductase) and against P-450 BNF-B2 and P-450 PB-B2, the major forms of P-450 isolated from liver microsomes of BNF- and PB-treated rats, respectively, were used to characterize the P-450-dependent monooxygenase system in the rat ventral prostate. Anti-P-450 reductase immunoglobulin G inhibited reduced nicotinamide adenine dinucleotide phosphate:cytochrome c reductase activity in prostatic microsomes, and anti-P-450 BNF-B2 but not anti-P-450 PB-B2 immunoglobulin G inhibited the BNF-induced prostatic microsomal 7-ethoxyresorufin O-deethylase and aryl hydrocarbon hydroxylase activities. A highly sensitive immunoblotting method was used to quantitate P-450 BNF-B2, P-450 PB-B2, and P-450 reductase in prostatic microsomes. Using this technique, prostatic P-450 reductase with a molecular weight corresponding to that of purified liver P-450 reductase was detected at a level of 0.02 nmol/mg of microsomal protein. In the liver, the same enzyme amounts to 0.2 nmol/mg of microsomal protein. P-450 BNF-B2 was not detected in prostatic microsomes from control or PB-treated rats, whereas a protein band with a molecular weight corresponding to that of purified liver P-450 BNF-B2 was found in prostatic microsomes from BNF-treated rats at a level of 0.05 nmol P-450 per mg microsomal protein. P-450 PB-B2 was not detected in prostatic microsomes from either control, PB-treated, or BNF-treated animals.
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PMID:Immunochemical detection and quantitation of microsomal cytochrome P-450 and reduced nicotinamide adenine dinucleotide phosphate:cytochrome P-450 reductase in the rat ventral prostate. 641 54

Male and female Sprague-Dawley rats were fed synthetic diets deficient in or supplemented with thiamin for 2 or 3 weeks. One group of rats receiving the thiamin-supplemented diet was pair-fed the amount consumed by rats fed the thiamin-deficient diet. One-half of each group was administered phenobarbital sodium for four consecutive days prior to decapitation. Rats fed the thiamin-deficient diet had higher NADPH cytochrome c reductase, aniline hydroxylase, and ethylmorphine N-demethylase activities than those fed high levels of thiamin. In addition, these animals generally responded more vigorously to induction by phenobarbital in their synthesis of microsomal protein, and increased activities of NADPH cytochrome c reductase, aniline hydroxylase, and ethylmorphine N-demethylase. Cytochrome P-450 concentration was higher in the microsomes from thiamin-deficient rats and was induced to a greater degree by phenobarbital than in microsomes from rats fed thiamin-supplemented diets ad libitum. Phenobarbital-enhanced metabolism of N-nitrosodimethylamine (DMN) by liver 9,000 g supernatant as evidenced by approximately two-fold increases in formaldehyde formed per gram liver. This increase in DMN metabolism in male rats is due at least in part to the increased concentration of microsomal protein, since metabolism per milligram microsomal protein was not increased. The fact that DMN metabolism per unit of microsomal cytochrome P-450 in phenobarbital-treated animals is decreased to about one-half of that in controls indicates that DMN is either metabolized by a non-cytochrome P-450-dependent system or that it is metabolized by a form of P-450 not induced by phenobarbital. A sex difference was evident in these experiments, females generally being more sensitive to the influence of varying levels of dietary thiamin. Also female rats but not males fed high-thiamin diets responded to phenobarbital with increased DMN metabolism per milligram microsomal protein.
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PMID:Influence of dietary thiamin on phenobarbital induction of rat hepatic enzymes responsible for metabolizing drugs and carcinogens. 643 11

Cyclophosphamide (CP) requires metabolic activation for its therapeutic action, and this metabolism results in the formation of two toxic metabolites, acrolein (ACR) and phosphoramide mustard (PM). To determine which metabolite is responsible for CP-induced lung injury, biochemical indices of toxicity and histopathologic changes in the lungs of CP-, ACR-, or PM-treated rats were evaluated. Experimental rats were given 200 mg kg-1 day-1 CP, 5 mg kg-1 day-1 ACR, or 50 mg kg-1 day-1 PM for 1 to 3 days, or were given 100 mg/kg CP for 1 day; control rats received vehicle alone for 1 to 3 days. Twenty-four hr after the last treatment the lungs were analyzed for (a) microsomal NADPH cytochrome c reductase and aniline hydroxylase activities; (b) microsomal lipid peroxide formation; and (c) glutathione content. In rats given 200 mg/kg CP, NADPH cytochrome c reductase and aniline hydroxylase activities decreased 66% (p less than 0.001) and 40% (p less than 0.001), respectively. Lipid peroxidation was increased 100 to 200% (p less than 0.001), and glutathione content was increased 60 to 70% (p less than 0.001). Similar but smaller changes were observed in the lungs of rats given 100 mg/kg CP. In rats given ACR, NADPH cytochrome c reductase and aniline hydroxylase activities decreased 66% (p less than 0.001) and 45% (p less than 0.001), and glutathione content increased 38% (p less than 0.05). In rats given PM, none of the biochemical variables examined were significantly altered. Phenobarbital and SKF 525-A prevented CP-induced biochemical alterations. Despite CP-induced biochemical alterations, no significant light microscopic changes were observed in the lungs. Alterations in lung mixed-function oxidase activity, GSH content, and microsomal lipid peroxide formation are early biochemical indices of CP-induced lung toxicity, and are due at least in part to the reactive metabolite ACR.
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PMID:Biochemical indices of cyclophosphamide-induced lung toxicity. 643 86

1 The effects of the hypolipidaemic agents ICI 53072 and clofibrate on cardiac output and its distribution to the hepatosplanchnic bed were determined by the use of radioactive microspheres in the rat. The effects of these agents on hepatic DNA content were compared with those of phenobarbitone. Also the effects of ICI 53072 on hepatic microsomal enzymes and bile flow were determined together with the effects of phenobarbitone. 2 ICI 53072 and clofibrate both increased liver size and liver blood flow. A daily dose of 25 mg kg-1 ICI 53072 for 5 days increased liver weight by 55% and liver blood flow by 43%, the latter by enhancing the proportion of cardiac output passing to the hepatosplanchnic bed. The increased liver blood flow with clofibrate (480 mg kg-1 daily for 5 days) was the result of greater cardiac output but the change (35%) was half the increase in liver weight. 3 Phenobarbitone (80 mg kg-1 daily for 5 days) produced a fall in DNA content per unit mass of liver but no change in hepatic DNA relative to body weight. ICI 53072 (25 mg kg-1 daily) increased hepatic DNA relative to body weight but by a lesser extent than it increased liver weight as a proportion of body weight; hence DNA content per unit mass of liver decreased. Clofibrate at three dose levels increased hepatic DNA relative to body weight but only one dose significantly decreased DNA content as a proportion of liver weight. 4 Phenobarbitone (80 mg kg-1 daily) increased bile flow whereas ICI 53072 (25 mg kg-1 daily) had no effect. Both treatments increased hepatic cytochrome P450 content and cytochrome c reductase activity. 5 It is concluded that phenobarbitone increases liver size by hepatocyte enlargement rather than cellular proliferation but that the hepatomegaly produced by the hypolipidaemic agents, at least at some doses, is due to a mixture of both processes. 6 It is further concluded that there is no simple relationship between the mechanism of hepatic enlargement resulting from drug treatment and changes in liver blood flow.
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PMID:Comparison of the effects of the hypolipidaemic agents ICI53072 and clofibrate with those of phenobarbitone on liver size, blood flow and DNA content in the rat. 683 62

In a search for airway epithelial mechanisms that may affect the subepithelial microcirculation, we examined plasma exudation responses to NG-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. L-NAME was applied topically on the tracheal mucosa of guinea pigs that had previously received 125I-albumin and/or colloidal gold particles (5 nm) intravenously. Luminal entry of plasma was determined by the levels of 125I-albumin in tracheal lavage fluid. Topical L-NAME (2.2, 9, and 22 mumol), but not intravenous L-NAME (375 mumol/kg), produced plasma exudation into the airway lumen (p < 0.01 to p < 0.001). The L-NAME enantiomer NG-nitro-D-arginine-methyl ester (D-NAME, 9 mumol) produced no exudative response. Coadministration of L-arginine (27 mumol) abolished the L-NAME-induced exudation. The extravasated plasma was distributed in the lamina propria and between epithelial cells (colloidal gold). The epithelial surface structure (scanning electron microscopy) appeared intact. Staining with nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase suggested that epithelial basal may contain nitric oxide synthases. We suggest that endogenously released nitric oxide from epithelial or other superficial cells tonically suppresses the macromolecular permeability of the subepithelial microcirculation.
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PMID:Mucosal nitric oxide may tonically suppress airways plasma exudation. 802 53


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