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)

Mitochondria and microsomes from whole rat testis, seminiferous tubules and Leydig cells were investigated with respect to their capacity to generate superoxide anion. In addition, lipid peroxidation by whole testis mitochondria and microsomes was measured. In the presence of NADH and various respiratory inhibitors all three mitochondrial preparations catalyzed the formation of superoxide anion at a rate of 0.27-1.67 nmol/min.mg. This formation was concluded to be confined mainly to the NADH dehydrogenase region of the respiratory chain. Addition of NADPH to whole testis or Leydig cell mitochondria, but not tubule mitochondria, caused an additional formation of superoxide anion, which was unrelated to the respiratory chain, accelerated several-fold by menadione, and presumably catalyzed by NADPH-cytochrome c reductase and cytochrome P-450. Microsomes isolated from whole testis, seminiferous tubules, and Leydig cells generated superoxide anion at rates between 0.19 and 0.44 nmol/min.mg. These rates were also strongly stimulated by menadione. It is likely that both NADPH-cytochrome c reductase and cytochrome P-450 were involved in the microsomal generation of superoxide. Free radical scavengers of various types inhibited both the mitochondrial and microsomal formation of superoxide anion. Lipid peroxidation in whole testis essentially paralleled superoxide anion generation. However, the rate of mitochondrial lipid peroxidation was twice that of the microsomal rate. It is concluded that seminiferous tubules and Leydig cells generate superoxide anion at different rates and by different mechanisms. Together with cytochrome P-450-dependent hydroxylases, e.g., BP and DMBA hydroxylases, this superoxide generation may reflect a potential for cell-specific peroxidative damage in the testis.
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PMID:Generation of superoxide anion and lipid peroxidation in different cell types and subcellular fractions from rat testis. 284 Jul 54

The effect of 28-day ethanol consumption on hamster liver microsomal electron transport systems and associated enzymatic activities has been examined. Microsomes isolated from ethanol-consuming hamsters showed increased levels of cytochrome P-450 and NADPH supported enzymatic activities. In contrast, reductions in the amount of cytochrome b5 and the NADH-supported rate of stearoyl-CoA desaturase were observed. NADH-cytochrome c reductase was decreased while a small increase in NADH-ferricyanide reductase was observed. These data suggest that decreased stearoyl-CoA desaturase activity is the result of lowered cytochrome b5 levels in microsomes isolated from ethanol-consuming hamsters.
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PMID:Differential effect of ethanol consumption on hamster liver microsomal electron transport systems. 286 Aug 17

The study is concerned with the effects of cimetidine (C), ranitidine (R) and oxmetidine (O) on rat liver cells, in order to compare the effects of increasing amounts of the drugs on various metabolic pathways and on hepatocyte morphology, and their relationship with the drug structure, namely the presence of an imidazole or furan ring. In vitro, an inhibition of ethylmorphine N-demethylase (E-DM) (60%) and of aniline hydroxylase (A-OH) (20%) was observed when either C or R were added at a concentration higher than 0.5 mM to microsomes from untreated rats. Microsomes from phenobarbital or 3-methylcholanthrene-pretreated animals showed a 30 to 40% inhibition of E-DM (mixed type inhibition). In vivo, administration of a single dose (475 microM/kg) of R was followed by an inhibition of E-DM activity, significantly less pronounced (p less than 0.05) than following an equimolar amount of C, whereas O did not alter the enzymatic activity. The amount of cytochrome P-450 and the activities of NADPH cytochrome c reductase and of A-OH were substantially unaffected. No changes of smooth endoplasmic reticulum or of other liver cell organelles were observed by electron microscopy. These findings demonstrate that both in vivo and in vitro E-DM appears as the more sensitive among the pathways considered. Moreover the data support the view that the mere presence of the imidazole ring does not account for the inhibitory effect of H2 antagonists.
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PMID:The effects of H2 receptor antagonists on hepatic microsomal drug metabolism and fine morphology of rat liver. 286 46

The effects of consecutive administration of 4-monomethylaminoantipyrine, a metabolite of aminopyrine, on the gamma-glutamyltranspeptidase activities of liver, kidney, urine and serum were investigated in rats. On day 5 after repeated treatment, a pronounced increase of gamma-glutamyltranspeptidase activity was seen in the liver homogenate as well as in the hepatic microsomes. Furthermore, simultaneous administration of 4-monomethylaminoantipyrine with phenobarbital increased to the same degree as compared with the single administration of aminopyrine. However, no change in gamma-glutamyltranspeptidase activity was observed in kidney, urine, serum and hepatic cytosolic fractions. Under the same experimental condition, the contents of cytochrome P-450 and b5, NADPH cytochrome c reductase, the activities of aminopyrine N-demethylase and aniline hydroxylase were also enhanced.
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PMID:Effect of repeated administration of monomethyl-aminoantipyrine on the activities of gamma-glutamyltranspeptidase and microsomal drug metabolizing enzymes in rat liver. 286 71

The effect of propylthiouracil (PTU) pretreatment on in vivo and in vitro oxidative drug metabolism was determined in the rat. Whereas pentobarbital sleeping time (PBST) and zoxazolamine paralysis time (ZZPT) were used as indices of in vivo drug metabolizing activity, biotransformation of aminopyrine and aniline by hepatic microsomal preparations were used as indices of in vitro drug metabolizing enzymes activities. PTU pretreatment significantly prolonged both PBST and ZZPT. Whereas PTU did not affect microsomal protein concentration or cytochrome P-450 content, it significantly decreased microsomal cytochrome c reductase and aniline hydroxylase activities. These changes in enzymatic activities were observed in microsomal preparations from either non-fasted or 24-hr fasted rats. Our results suggest that PTU-induced hypothyroidism modifies the metabolism and effectiveness or toxicity of concomitantly administered drugs.
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PMID:Inhibitory effect of propylthiouracil-induced hypothyroidism in rat on oxidative drug metabolism. 286 58

Adult, male rats were infected with 20 metacercariae of Fasciola hepatica given orally, other rats were left untreated. Five weeks after infestation, some animals received phenobarbitone, 3-methylcholanthrene, beta-naphthoflavone or Arochlor 1254, to induce liver drug metabolizing enzymes. Fascioliasis provoked decreases in aminopyrine N-demethylase, aniline hydroxylase, the mutagenic activity of cyclophosphamide and cytochrome P-450 concentration in untreated or phenobarbitone or Arochlor pretreated rats. In contrast, cytochrome b5, NADPH cytochrome c reductase, ethyoxycoumarin O-deethylase and the enzymatic activation of ethidium bromide were not affected by fascioliasis whatever pretreatment was given. Fascioliasis decreased liver drug metabolizing enzymes which were specifically induced by both phenobarbitone and Arochlor, this could be due to either the specific action of toxic excretions of flukes or to the particular localization of tissue damage within the liver lobule.
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PMID:Induction of drug metabolizing enzymes in the liver of rats infested with Fasciola hepatica. 286 51

Microsomes from Maja crispata hepatopancreas contain all the components of the functional mixed function oxidase system: cytochrome P-450 (0.47 nmol/mg), the activity of NADPH cytochrome c reductase (12.25 nmol/mg/min) and benzo[a]pyrene monooxygenase activity (6.58 pmol/mg/min). Solubilization of hepatopancreas microsomes with sodium cholate, and affinity chromatography on omega-amino-n-octyl Sepharose 4B, gave a single cytochrome P-450 peak eluting with 0.2% Emulgen 913. DEAE cellulose chromatography of this cytochrome peak gave rise to a single haemoprotein peak, with apparent monomer Mr = 53,500, as determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis.
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PMID:Purification and characterization of a single form of cytochrome P-450 from the spiny crab Maja crispata. 286 93

Glucuronidation of 4-nitrophenol, nopol (a monoterpenoid alcohol) and bilirubin, which in the rat, are catalyzed by three different enzymes, has been examined in liver biopsies from patients with various liver diseases, in particular cholestasis. These different activities were not correlated, which strongly suggests that at least three independently regulated forms of UDP-glucuronosyltransferases were present in the microsomes. Non ionic detergents (Triton X100, Emulgen 911) and deoxycholate produced similar activation (more than 2-fold) of the glucuronidation of 4-nitrophenol. Amphipathic substances, such as CHAPS (3-[3-cholamidopropyl-dimethylammonio]-1-propane sulfonate), and lysophosphatidylcholines maximally increased this UDP-glucuronosyltransferase activity, the most potent being oleoyl lysophosphatidylcholine (4-fold increase). Discriminant analysis of the data revealed no correlation between the three different UDP-glucuronosyltransferase activities and the age or sex of the patients. A good correlation was found on multidimensional analysis between form 1 of the enzyme (4-nitrophenol glucuronidation) and, in decreasing order of magnitude, epoxide hydrolase (measured with benzo(a)pyrene-4,5-oxide as substrate), cytochrome P-450, 7-ethoxycoumarin deethylase, aspartate aminotransferase and gamma-glutamyltransferase (r = 0.89); and between Form 3 of the enzyme (bilirubin glucuronidation) and NADPH cytochrome c reductase, alkaline phosphatase, (r = 0.81). These relationships may reflect the differential variation in enzymatic activities in various hepato-biliary diseases.
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PMID:Properties of human hepatic UDP-glucuronosyltransferases. Relationship to other inducible enzymes in patients with cholestasis. 288 32

Experiments were undertaken to examine the ability of selenium to protect against acetaminophen-induced hepatotoxicity and to examine possible mechanisms for this protective effect. Pretreatment of male, Sprague-Dawley rats with sodium selenite (12.5 mumol Se/kg, ip) 24 hr prior to acetaminophen administration produced a significant protection against the hepatotoxic effects of acetaminophen as assessed by a decrease in the plasma appearance of alanine aminotransferase and aspartate aminotransferase activities following acetaminophen. This was accompanied by an increase in the hepatic glutathione levels in selenium-treated animals and an inhibition in the decrease in hepatic glutathione content observed in animals receiving hepatotoxic doses of acetaminophen. Selenium pretreatment decreased the in vivo covalent binding of acetaminophen metabolites to hepatic protein, but did not alter hepatic microsomal cytochrome P-450 content or NADPH cytochrome c reductase activity, suggesting that selenium does not significantly alter the metabolism of acetaminophen to reactive electrophilic metabolites by the cytochrome P-450-dependent mixed-function oxidase enzyme system. Selenium produced an increase in the activity of gamma-glutamylcysteine synthetase which may account for the increased glutathione availability in selenium-treated animals and increased the activities of glutathione S-transferase and glucose-6-phosphate dehydrogenase. Examination of the urinary metabolite profile in selenium-treated animals revealed that the urinary excretion of acetaminophen and its metabolites was significantly increased over a 72-hr period. The increase occurred in the AAP-glucuronide metabolite while parent AAP and AAP-sulfate were actually decreased in selenium-treated rats. No change in recovery was observed in the AAP-glutathione or AAP-mercapturate urinary metabolites. While the glutathione conjugating system is enhanced by selenium treatment, amelioration of acetaminophen toxicity is most likely the result of enhanced glucuronidation which effectively diverts the amount of acetaminophen to be converted by the cytochrome P-450 system to the toxic metabolite.
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PMID:Protective effects of selenium on acetaminophen-induced hepatotoxicity in the rat. 290 Nov 47

Metabolism of l-menthol in rats was investigated both in vivo and in vitro. Metabolites isolated and characterized from the urine of rats after oral administration (800 mg/kg of body weight/day) of l-menthol were the following: p-menthane-3,8-diol (II), p-menthane-3,9-diol (III), 3,8-oxy-p-menthane-7-carboxylic acid (IV), and 3,8-dihyroxy-p-menthane-7-carboxylic acid (V). In vivo, the major urinary metabolites were compounds II and V. Repeated oral administration (800 mg/kg of body weight/day) of l-menthol to rats for 3 days resulted in the increase of both liver microsomal cytochrome P-450 content and NADPH-cytochrome c reductase activity by nearly 80%. Further treatment (for 7 days total) reduced their levels considerably, although the levels were still higher than the control values. Both cytochrome b5 and NADH-cytochrome c reductase levels were not changed during the 7 days of treatment. Rat liver microsomes readily converted l-menthol to p-menthane-3,8-diol (II) in the presence of NADPH and O2. This activity was significantly higher in microsomes obtained from phenobarbital (PB)-induced rats than from control microsomal preparations, whereas 3-methylcholanthrene (3-MC)-induced microsomes failed to convert l-menthol to compound II in the presence of NADPH and O2. l-Menthol elicited a type I spectrum with control (Ks = 60.6 microM) and PB-induced (Ks = 32.3 microM) microsomes whereas with 3MC-induced microsomes it produced a reverse type I spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies on the metabolism of l-menthol in rats. 290 4


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