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MeSH: oleandomycin

14 záznamů v PubMed Filtry

Článek

Effects of cytochrome P450 inhibitors on peroxidase activity

Neuro endocrinology letters. 2012 ; 33 Suppl 3 () : 33-40.

Neuro Endocrinol Lett
ISSN 0172-780X
Zdroj

OBJECTIVES: Of several enzymes metabolizing xenobiotics, cytochrome P450 (CYP) and peroxidase enzymes seem to be most important. One of the major challenges in studies investigating metabolism of xenobiotics is to resolve which of these two groups of enzymes is predominant to metabolize individual xenobiotic compounds. Utilization of selective inhibitors of CYP and peroxidase enzymes might be a useful tool to identify the contribution of these enzymes to metabolism of xenobiotics in samples, where both types of enzymes are present. The aim of this study was to investigate specificities of several known CYP inhibitors to these enzymes; whether they inhibit only the CYP enzymes and do not inhibit peroxidases. METHODS: Since the oxidation of o-anisidine catalyzed by a model peroxidase used, horseradish peroxidase (HRP), is a two-substrate reaction, the inhibition potential of tested chemicals was studied with respect to both peroxidase substrates, o-anisidine and hydrogen peroxide. Initial velocities of o-anisidine oxidation by HRP under various conditions were determined spectrophotometrically. RESULTS: The CYP inhibitors metyrapone, troleandomycine, disulfiram, sulfaphenazole, quinidine and 1-aminobenzotriazole do not inhibit o-anisidine oxidation catalyzed by HRP. In contrast, ketoconazole, diethyldithiocarbamate, ellipticine, α-naphtoflavone, proadifen SKF525A, piperonylbutoxide, were found to inhibit not only the CYPs, but also the HRP-mediated oxidation of o-anisidine. Interestingly, α-naphtoflavone inhibits oxidation of o-anisidine by HRP with respect to H2O2, but not with respect to o-anisidine. Diethyldithiocarbamate is the most potent peroxidase inhibitor of o-anisidine oxidation with Ki with respect to o-anisidine of 10 μM and Ki with respect to H2O2 of 60 μM, being even the better peroxidase inhibitor than the classical "peroxidase inhibitor" - propyl gallate (Ki with respect to o-anisidine of 60 μM and Ki with respect to H2O2 of 750 μM). CONCLUSIONS: The results of the present study demonstrate that 1-aminobenzotriazole, a potent inhibitor of various CYP enzymes, seems to be the best candidate suitable for utilization in studies evaluating participation of CYP enzymes in metabolism of xenobiotics in various complex biological materials containing both CYP and peroxidase enzymes. Moreover, precaution to prevent misinterpretation of results is necessary in cases when proadifen SKF525A, piperonylbutoxide, diethyldithiocarbamate, ketoconazole, α-naphtoflavone and ellipticine are used in similar studies (as CYP inhibitors in various complex biological materials containing both CYP and peroxidase enzymes), since these chemicals can except of CYP enzymes inhibit also peroxidase-mediated reactions.

MeSH
aktivace enzymů účinky léků MeSH
benzoflavony chemie farmakologie MeSH
chinidin chemie farmakologie MeSH
disulfiram chemie farmakologie MeSH
dithiokarb chemie farmakologie MeSH
elipticiny chemie farmakologie MeSH
inhibitory cytochromu P450 * MeSH
inhibitory enzymů chemie farmakologie MeSH
ketokonazol chemie farmakologie MeSH
křenová peroxidasa antagonisté a inhibitory metabolismus MeSH
lidé MeSH
metyrapon chemie farmakologie MeSH
piperonylbutoxid chemie farmakologie MeSH
proadifen chemie farmakologie MeSH
substrátová specifita účinky léků MeSH
sulfafenazol chemie farmakologie MeSH
triazoly chemie farmakologie MeSH
troleandomycin chemie farmakologie MeSH
vztahy mezi strukturou a aktivitou MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
srovnávací studie MeSH
Názvy látek
1-aminobenzotriazole MeSH Prohlížeč
alpha-naphthoflavone MeSH Prohlížeč
benzoflavony MeSH
chinidin MeSH
disulfiram MeSH
dithiokarb MeSH
elipticiny MeSH
ellipticine MeSH Prohlížeč
inhibitory cytochromu P450 * MeSH
inhibitory enzymů MeSH
ketokonazol MeSH
křenová peroxidasa MeSH
metyrapon MeSH
piperonylbutoxid MeSH
proadifen MeSH
sulfafenazol MeSH
triazoly MeSH
troleandomycin MeSH

Článek

Different in vitro metabolism of paclitaxel and docetaxel in humans, rats, pigs, and minipigs

Drug metabolism and disposition: the biological fate of chemicals. 2004 Jun ; 32 (6) : 666-74.

Drug Metab Dispos
ISSN 0090-9556
Zdroj

We investigated cytochrome P450 (P450)-catalyzed metabolism of the important cancer drugs paclitaxel and docetaxel in rat, pig, minipig, and human liver microsomes and cDNA-expressed P450 enzymes. In rat microsomes, paclitaxel was metabolized mainly to C3'-hydroxypaclitaxel (C3'-OHP) and to a lesser extent to C2-hydroxypaclitaxel (C2-OHP), di-hydroxypaclitaxel (di-OHP), and another unknown monohydroxylated paclitaxel. In pig and minipig microsomes, this unknown hydroxypaclitaxel was the main metabolite, whereas C3'-OHP was a minor product. In minipigs, C2-OHP was the next minor product. In human liver microsomes, 6 alpha-hydroxypaclitaxel (6 alpha-OHP) was the main metabolite, followed by C3'-OHP and C2-OHP. Among different cDNA-expressed human P450 enzymes (CYP1A2, 1B1, 2A6, 2C9, 2E1, and 3A4), only CYP3A4 enzyme formed C3'-OHP and C2-OHP. Docetaxel was metabolized in pig, minipig, rat, and human liver microsomes mainly to hydroxydocetaxel (OHDTX), whereas CYP3A-induced rat microsomes produced primarily diastereomeric hydroxyoxazolidinones. Human liver microsomes from 10 different individuals formed OHDTX at different rates correlated with CYP3A4 content. Troleandomycin as a selective inhibitor of CYP3A inhibited the formation of C3'-OHP, C2-OHP, and di-OHP, as well as the unknown OHP produced in rat, minipig, and pig microsomes. In human liver microsomes, troleandomycin inhibited C3'-OHP and C2-OHP formation, and a suitable inhibitor of human CYP2C8, fisetin, strongly inhibited the formation of 6 alpha-OHP, known to be catalyzed by human CYP2C8. In conclusion, the metabolism of docetaxel is the same in all four species, but metabolism of paclitaxel is different, and 6 alpha-OHP remains a uniquely human metabolite. Pigs and minipigs compared with each other formed the same metabolites of paclitaxel.

MeSH
docetaxel MeSH
dospělí MeSH
druhová specificita MeSH
flavonoidy farmakologie MeSH
flavonoly MeSH
fytogenní protinádorové látky metabolismus MeSH
inhibitory enzymů farmakologie MeSH
izoenzymy metabolismus MeSH
jaterní mikrozomy enzymologie MeSH
kinetika MeSH
krysa rodu Rattus MeSH
lidé MeSH
miniaturní prasata MeSH
mladiství MeSH
paclitaxel antagonisté a inhibitory metabolismus MeSH
potkani Wistar MeSH
prasata MeSH
systém (enzymů) cytochromů P-450 metabolismus MeSH
taxoidy metabolismus MeSH
techniky in vitro MeSH
troleandomycin farmakologie MeSH
zvířata MeSH
Check Tag
dospělí MeSH
krysa rodu Rattus MeSH
lidé MeSH
mladiství MeSH
mužské pohlaví MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Research Support, U.S. Gov't, P.H.S. MeSH
srovnávací studie MeSH
Názvy látek
docetaxel MeSH
fisetin MeSH Prohlížeč
flavonoidy MeSH
flavonoly MeSH
fytogenní protinádorové látky MeSH
inhibitory enzymů MeSH
izoenzymy MeSH
paclitaxel MeSH
systém (enzymů) cytochromů P-450 MeSH
taxoidy MeSH
troleandomycin MeSH

Článek

Flexibility and stability of the structure of cytochromes P450 3A4 and BM-3

European journal of biochemistry. 2000 May ; 267 (10) : 2916-20.

Eur J Biochem
ISSN 0014-2956
Zdroj

The flexibility of the structure and compressibility of the respective active site of cytochromes P450 3A4 (CYP3A4) and BM-3 (CYP102) were studied using absorption spectroscopy in the ultraviolet and visual regions. Conformational changes in the overall protein structures of both CYP3A4 and CYP102 due to the effects of temperature and pressure are reversible. However, the enzymes differ in the properties of their active sites. The CYP3A4 enzyme denatures to the inactive P420 form relatively easy, at 3000 bar over half is converted to P420. The compressibility of its active site is lower than that of CYP102 and is greater with the substrate bound, which is in line with the observed lack of a stabilizing effect of the substrate on its conformation under pressure. In contrast, CYP102, although having the most compressible active site among the P450s, possesses a structure that does not denature easily to the inactive (P420) form under pressure. In this respect, it resembles the P450 isolated from acidothermophilic archaebacteria [McLean, M.A., Maves, S.A., Weiss, K.E., Krepich, S. & Sligar, S.G. (1998) Biochem. Biophys. Res. Commun. 252, 166-172].

Článek

Presence and activity of cytochrome P450 isoforms in minipig liver microsomes. Comparison with human liver samples

Drug metabolism and disposition: the biological fate of chemicals. 1998 Jan ; 26 (1) : 56-9.

Drug Metab Dispos
ISSN 0090-9556
Zdroj

Cytochrome P450 (CYP) of the 3A family (CYP3A) has been detected in minipig liver microsomes by immunochemical screening (Western blotting), revealing bands that co-migrate with human CYP3A4 and 3A5. The nifedipine oxidase activity and testosterone 6beta-hydroxylating activity (specific markers for CYP3A enzymes) of the human liver microsomal and minipig liver microsomal samples were comparable, as were the results of specific inhibition of this activity by triacetyloleandomycin. The presence of CYP1A, 2A, 2C, 2D, and 2E1 marker activities in minipig liver microsomes was found by testing with the respective specific substrates (7-ethoxyresorufin, coumarin, tolbutamide, bufuralol, and chlorzoxazone). 7-Pentoxyresorufin O-depentylase activity (indicative of CYP2B) was absent from minipig as well as human liver microsomal samples. The results indicate that minipigs might be, in many cases, the most suitable experimental animals to predict biotransformation pathways in humans, because the activity of the most important CYP isoform in humans (CYP3A, metabolizing the majority of known drug substrates) is present in minipigs, with comparable levels and activities. Moreover, there is no need to induce CYP enzyme levels.

MeSH
antibakteriální látky farmakologie MeSH
cytochrom P-450 CYP3A MeSH
izoenzymy metabolismus MeSH
jaterní mikrozomy enzymologie MeSH
katalýza MeSH
lidé MeSH
miniaturní prasata metabolismus MeSH
nifedipin antagonisté a inhibitory metabolismus MeSH
oxidace-redukce účinky léků MeSH
prasata MeSH
systém (enzymů) cytochromů P-450 metabolismus MeSH
troleandomycin farmakologie MeSH
zvířata MeSH
Check Tag
lidé MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
srovnávací studie MeSH
Názvy látek
antibakteriální látky MeSH
CYP3A protein, human MeSH Prohlížeč
CYP3A4 protein, human MeSH Prohlížeč
cytochrom P-450 CYP3A MeSH
izoenzymy MeSH
nifedipin MeSH
systém (enzymů) cytochromů P-450 MeSH
troleandomycin MeSH

Článek

Induction of mutants resistant to antibiotics in Brevibacterium flavum

Folia microbiologica. 1986 ; 31 (2) : 94-7.

Folia Microbiol (Praha)
ISSN 0015-5632
Zdroj

The optimum conditions for the induction of mutants resistant to antibiotics in Brevibacterium flavum ATCC 14067 were determined. UV irradiation at the energy fluence of 6.5 kJ/m2 and N-methyl-N'-nitro-N-nitrosoguanidine (1 mg/mL) at pH 6.0 were used for the induction of mutants. Mutant strains resistant to rifampicin, oleandomycin, streptomycin and erythromycin were prepared.

MeSH
antibakteriální látky farmakologie MeSH
antibiotická rezistence MeSH
Brevibacterium účinky léků genetika účinky záření MeSH
erythromycin farmakologie MeSH
koncentrace vodíkových iontů MeSH
methylnitronitrosoguanidin farmakologie MeSH
mutace MeSH
neomycin farmakologie MeSH
oleandomycin farmakologie MeSH
rifampin farmakologie MeSH
streptomycin farmakologie MeSH
ultrafialové záření MeSH
vankomycin farmakologie MeSH
Publikační typ
časopisecké články MeSH
Názvy látek
antibakteriální látky MeSH
erythromycin MeSH
methylnitronitrosoguanidin MeSH
neomycin MeSH
oleandomycin MeSH
rifampin MeSH
streptomycin MeSH
vankomycin MeSH

Článek

Sensitivity to macrolide antibiotics and lincomycin in Francisella tularensis holarctica

Journal of hygiene, epidemiology, microbiology, and immunology. 1980 ; 24 (1) : 84-91.

J Hyg Epidemiol Microbiol Immunol
ISSN 0022-1732
Zdroj

Among the 345 F. tularensis holarctica strains isolated in Europe, Asia and North America, two variants were found: one sensitive and the other resistant to erythromycin, oleandomycin and lincomycin. These characteristics were not associated with virulence, antigenicity, biochemical activity or source of isolation and displayed high stability in passages in laboratory animals or multiple passages in culture media. The two variants are proposed to be designated as biotype (biovar) I, erythromycin sensitive (erys), and biotype (biovar)II, erythromycin resistant (eryR). A predominance of biotype I was observed for western Europe, eastern Siberia and the Far East, as well as North America, whereas biotype II prevailed in central Europe, the European part of USSR, especially the south, and western Siberia. The distribution of biotype II largely coincided with the habitat area of Arvicola terrestris, from which it was isolated with the highest frequency. Within the areas of biotype II prevalence, erythromycin and other macrolide antibiotics, as well as lincomycin should not be used for tularemia therapy.