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)

SVA was used to separate liver cells from rats pretreated for 3 days with PB (40 mg/kg intraperitoneally, twice daily) or 3-MC (50 MG/KG AS A SINGLE INJECTIOn). Twelve fractions of cells were collected with s's ranging from 97 mm/hr (fraction1) to 25 mm/hr (fraction 12). Cells in each fraction were sized and counted electronically. PB caused the average volume of the largest cells recovered (fraction 1) to increase to 16, 725 micrometer3 from 10,500 micrometer3 previously reported in untreated animals. The number of cells recovered in the fast-sedimenting fractions (1 to 6) also increased, but there was only a small rise in the average model volume of hepatocytes determined prior to SVA. In cell suspensions analyzed after PB treatment no evidence was found for a discontinuity in the distribution of density-volume characteristics as previously described in hepatocytes from untreated rats. As expected, prior to sedimentation analysis, hepatocyte suspensions from rats treated with PB contained increased cytochrome P-450. The average ratio (n = 4) of P-450 in separated to unseparated cells ranged from 2.75 (fractions 1 + 2) to 0.38 (fractions 11 + 12), giving a 6.8-fold range in quantity of cytochrome per cell. Over this range, cell volume increased 4.2-fold, indicating a gradient in P-450 concentration similar to that previously reported to exist in cells from untreated rat liver. The gradient for AHH activity was 6.7-fold, suggesting that activity of MFO's paralleled the increase in cytochrome concentration. 3-MC pretreatment caused no significant increase in either size or number of cells in the fast-sedimenting fractions, but the discontinuity in density-volume characteristics which distinguished fast and slow sedimenting cells of untreated rats became marked. Furthermore, both the size and number of cells recovered in fractions 7 to 11 (which include the modal peal volume of unseparated hepatocytes) were increased. The gradient of P-450 (OR P1-450) was less steep in 3-MC-treated cells with pooled fractions 1 and 2 containing an average of 4.62 times as much cytochrome as fractions 11 and 12. The gradient for AHH was 4.29 times. The range of cell volume was 3.3-fold over this range. Additional experimental work was performed to determine whether P-450, AHH, or NADPH cytochrome c reductase exhibited differences in activity or concentration per unit of cell volume between cells on either side of fraction 7 where discontinuity had been noted. Each variable was expressed per unit of cell volume in fractions 5 and 9; ratios were compared but were indistinguishable from unity. It was concluded that induction of MFO activity had occurred equally in both populations of cells. Densities were calculated from s and cell volume. Noticeable loss of density followed PB treatment in cells of all sizes. 3-MC had less of an effect on density but enhanced the increment in density observed at fraction 7, which corresponds to the division between cells with distinct sedimentation characteristics...
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PMID:Effects of phenobarbital and 3-methylcholanthrene pretreatment on size, sedimentation velocity, and mixed function oxygenase activity of rat hepatocytes. 41

The results show that a cholesterol-rich diet changes the composition of mucosal membranes. A high cholesterol diet increases mucosal cholesterol and phospholipid contents. Cholesterol enhanced mucosal NADPH cytochrome c reductase and aryl hydrocarbon hydroxylase activities as well as mucosal UDP glucuronosyltransferase activity. When phenobarbitone or Clophen A 50 or 60 were administered intraperitoneally to cholesterol-fed rats, the hydroxylation and glucuronidation activities decreased to a lower level. 3-Methylcholanthrene was, however, able to maintain or increase mucosal hydroxylative enzymes and UDP glucuronosyltransferase. These results indicate that the drug-metabolizing enzymes of the intestinal mucosa behave very differently from those in the liver. Diet apparently has a regulatory effect on the induction of drug-metabolizing enzymes because only a very potent inducer, 3-methylcholanthrene, was able to maintain and even induce mucosal drug-metabolizing enzymes in rats fed on a high cholesterol diet, possibly through changes in the microenvironment of enzymes caused by cholesterol.
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PMID:Inducibility of mucosal drug-metabolizing enzymes of rats fed on a cholesterol-rich diet by polychlorinated biphenyl, 3-methylcholanthrene and phenobarbitone. 81 Aug 14

The activities of enzymes related to energy metabolism in the gastrocnemius and soleus muscles in young-adult (4 months), mature (12 months), and senescent (24 months) rats were compared after continuous (72 consecutive h) exposure to normobaric hypoxia or normoxia after the vasodilator naftidrofuryl or saline solution had been given intraperitoneally for 30 consecutive days. The maximum rats (Vmax) of the following enzyme activities in the crude extract and/or the crude mitochondrial fraction of each muscle specimen were evaluated for: the anaerobic glycolytic pathway (hexokinase, phosphofructokinase, pyruvate kinase, and lactate dehydrogenase), the tricarboxylic acid cycle (citrate synthase, and malate dehydrogenase), the electron transfer chain (cytochrome oxidase), and the NAD+/NADH redox state (total NADH cytochrome c reductase). The significance of differences between the enzyme activities at different ages or under different experimental conditions in the two tissue preparations of the two muscles were determined by ANOVA. MCA and ETA2 were used to evaluate the net effects of the experimental conditions. First, aging did not seem to affect the soleus and gastrocnemius muscles in the same way. In the gastrocnemius muscle, the major changes were seen in enzymes of the glycolytic pathway, in the crude extracts. In the soleus muscle, the more striking changes in enzyme activities as a function of aging were found in the crude mitochondrial fraction. We also found that hypoxia caused more important changes in 12-month-old rats than in those of other ages (especially the enzyme activities of the gastrocnemius muscle). Naftidrofuryl modified the effects of hypoxia only sometimes and further investigations are necessary before we can draw any conclusions about the pharmacological activity of naftidrofuryl in hypoxia.
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PMID:Effects of hypoxia and pharmacological treatment on enzyme activities in skeletal muscle of rats of different ages. 164 27

Renal cortical metabolism of drugs and xenobiotics was assessed with microsomes prepared from normal, contralateral and 4-day postobstructive hydronephrotic kidneys. Microsomal mixed-function oxidase and prostaglandin H synthase systems were determined in control and 3-methylcholanthrene-treated rabbits. Cytochrome P450 content and biphenyl-4-hydroxylase activity but not cytochrome c reductase activity were reduced in the hydronephrotic kidney. 3-Methylcholanthrene treatment increased cytochrome P450 content and biphenyl-4-hydroxylase and acetanilide-4-hydroxylase activities in normal, contralateral, and hydronephrotic kidneys. However, even after 3-methylcholanthrene treatment, hydronephrotic kidney cytochrome P450 content and acetanilide-4-hydroxylase activity were not more than 20% of the corresponding normal kidney values. Prostaglandin H synthase metabolism of benzidine was observed in the hydronephrotic kidney but was at the limit of detection in normal or contralateral kidneys with or without 3-methylcholanthrene treatment. Characteristics of benzidine metabolism were consistent with the hydroperoxidase rather than the fatty acid cyclooxygenase activity of prostaglandin H synthase. Therefore, hydronephrosis alters the drug and xenobiotic metabolic profile of the renal cortex from a primarily mixed-function oxidase-dependent system to one with the potential for metabolism by the hydroperoxide component of prostaglandin H synthase.
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PMID:Renal cortical drug and xenobiotic metabolism following urinary tract obstruction. 643 98

A series of naphthalene diols, quinones, and related compounds were examined for their ability to inhibit mixed-function oxidase in liver microsomes obtained from rats which had been pretreated with 3-methylcholanthrene (3-Mc) or phenobarbital (PB). Using benzo(a)pyrene monooxygenase as a measure of mixed-function oxidase activity, it was found that phenanthrene-9, 10-quinone was the most active compound tested with a K1 = 0.79 microM. Phenanthrene-9, 10-quinone did not affect cytochrome c reductase but did inhibit aminopyrine N-demethylase and p-nitroanisole-O-demethylase in both 3-MC and PB-induced microsome with almost identical inhibition constants. 1,2-Naphthoquinone exerted similar effects as phenanthrene-9,10-quinone on cytochrome c reductase, aminopyrine N-demethylase and p-nitroanisole-O-demethylase. Both quinones stimulated NADPH oxidase activity but the extent of this stimulation did not explain their inhibition of microsomal oxidation. Kinetic studies using benzo(a)-pyrene monooxygenase with phenanthrene-9, 10-quinone and 1,2-naphthoquinone indicated that they were noncompetitive with benzo(a)pyrene and mixed noncompetitive with NADPH. Both of these quinones inhibited benzo(a)pyrene induced oncogenic transformation in C3H10T1/2CL8 cells in culture in a dose response manner, presumably by inhibition of the cellular microsomal enzyme which activate benzo(a)pyrene. Phenanthrene-9, 10-quinone and 1,2-naphthoquinone seem to inhibit microsomal oxidative processes by interaction at the level of cytochrome P-450 possibly with a cytochrome P-450-substrate-oxygen complex.
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PMID:Inhibition of microsomal metabolism and chemical oncogenesis in culture by naphthalene quinones. 721 45

The activities of enzymes related to energy metabolism in the gastrocnemius and soleus muscles in young-adult (4 months), mature (12 months) and senescent (24 months) rats were compared after 72 h of continuous exposure to normobaric hypoxia or normoxia after alpha-adrenergic antagonist nicergoline or saline solution had been given intraperitoneally for 30 consecutive days. The maximum rates (Vmax) of the following enzyme activities in the crude extract and/or the mitochondrial fraction of each muscle specimen were evaluated: (1) for the anaerobic glycolytic pathway: hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase; (2) for the tricarboxylic acid cycle; citrate synthase and malate dehydrogenase; (3) for the electron transfer chain; cytochrome oxidase; and (4) for the NAD+/NADH redox state: total NADH cytochrome c reductase. The significant differences between the enzyme activities at different ages or under different experimental conditions in the two tissue preparations of the two muscles were determined by ANOVA. MCA and ETA were used to evaluate the net effects of the experimental conditions. Ageing did not seem to affect the soleus and gastrocnemius muscles in the same way. Changes were seen only in the glycolytic pathway enzymes in the crude extract from the gastrocnemius muscle. In the soleus muscle changes in enzyme activities as a function of ageing were also found in the mitochondrial fraction. We also found that hypoxia caused greater changes in 12-month-old rats than in those of other ages (especially in the enzyme activities of the gastrocnemius muscle). Finally out data show that only in certain cases was the pharmacological treatment able to modify the influence of hypoxic conditions on the levels of enzyme activities, regardless of the age of animals.
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PMID:Effects of hypoxia on enzyme activities in skeletal muscle of rats of different ages. An attempt at pharmacological treatment. 873 89

Phenobarbital (PB; 80 mg/kg, ip) or 3-methylcholantrene (3-MC; 20 mg/kg, ip) was administered to Wistar male rats at the end of the feeding period of 30 days and the effects of food restriction (FR) and FR followed by inducer treatment on hepatic drug metabolizing enzymes, microsomal electron transport components, NADPH dependent lipid peroxidation and glutathione-s-transferase activities were studied. In both, PB and 3-MC treatment, the magnitude of increase in microsomal protein content, cytochrome b5 and aminopyrine N-demethylase (APND) activity was less in FR animals than in ad libitum fed; while cytochrome P-450 levels and activities of cytochrome c reductase and acetanilide hydroxylase (ACOH) were higher in FR animals. NADPH dependent lipid peroxidation and cytosolic glutathione-s-transferase activity were also enhanced due to PB and 3-MC treatment but the magnitude of increase was less in FR animals. The ACOH activity increased to a greater extent than APND activity in FR animals following PB and 3-MC treatment. It is suggested that the response to inducers in the FR animals differ from that in the ad libitum fed rats.
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PMID:Effect of inducers on hepatic microsomal mixed function oxidase system of male rats during food restriction. 927 33