• Western blotting revealed that the absorbed anti-human CYP2C9 preparation reacted with only recombinant CYP2C9 and the corresponding native protein in hepatic microsomes, and no longer recognized CYP2C19 and CYP2C8. (aspetjournals.org)
  • 15%) inhibitory effect on S -mephenytoin 4′-hydroxylation by purified CYP2C19 or hepatic microsomes containing CYP2C19. (aspetjournals.org)
  • Using the HPLC method, CYP1A1, 2C and 3A specific activities in hepatic microsomes isolated from exposed rats were analyzed. (nel.edu)
  • Incubation of racemic methylenedioxyamphetamine (MDA) or methylenedioxymethamphetamine (MDMA) with rat hepatic microsomes, in the presence of NADPH, generated a spectrally observed inhibitory complex with cytochrome P-450. (erowid.org)
  • In contrast, 3-methylbenzotriazinone, a structural analogue, was metabolized by hepatic microsomes to afford benzotriazinone and a hydrophilic metabolite. (aston.ac.uk)
  • Catabolism of 3'-azido-3'-deoxythymidine in hepatocytes and liver microsomes, with evidence of formation of 3'-amino-3'-deoxythymidine, a highly toxic catabolite for human bone marrow cells. (aspetjournals.org)
  • Studies using rat and human liver microsomes demonstrated that the rate of formation of AMT and GAMT increased in the presence of NADPH, suggesting the involvement of a NADPH-dependent enzyme system. (aspetjournals.org)
  • In human liver microsomes, ratios of 4-OH-ALP/alpha-OH-ALP reaction velocities calculated at clinically relevant plasma concentrations of ALP ranged from 7 to 17, qualitatively consistent with, but numerically larger than, the ratio of the plasma levels of the two metabolites during clinical use of ALP in humans. (nih.gov)
  • Monospecific anti-CYP2C9 was also found to inhibit rates of tolbutamide hydroxylation by 93 ± 4 and 78 ± 6% in CYP2C19-deficient and CYP2C19-containing human liver microsomes, respectively. (aspetjournals.org)
  • Taken together, our results indicate that both CYP2C9 and CYP2C19 are involved in tolbutamide hydroxylation by human liver microsomes, and that CYP2C19 underlies at least 14 to 22% of tolbutamide metabolism. (aspetjournals.org)
  • Interestingly, the same adduct was formed when flutamide was incubated with human liver microsomes in the presence of GSSG and NADPH. (unboundmedicine.com)
  • In-vitro metabolic inhibition studies using rat and human liver microsomes and intestinal absorption studies of riluzole in a rat everted gut-sac model were conducted to elucidate the mechanism of interaction. (researchgate.net)
  • In vitro and clinical studies were conducted on human liver microsomes and healthy human subjects, respectively. (hindawi.com)
  • The human liver microsomes were employed for in vitro investigation, while in vivo study was conducted on healthy human subjects. (hindawi.com)
  • In the present study we further examined the roles of several human P450 enzymes, as well as P450 2D6, in the hydroxylation of (+/-)-bufuralol, using liver microsomes from several human samples and human P450 enzymes expressed in human lymphoblastoid cell lines or Escherichia coli. (unboundmedicine.com)
  • Quinidine and anti-rat P450 2D1 antibody almost completely inhibited bufuralol 1'-hydroxylation in human sample HL-18 at a substrate concentration of 0.4 mM, whereas these effects were not so drastic when liver microsomes from human sample HL-67 were used. (unboundmedicine.com)
  • At least five other, minor, bufuralol products were formed by human liver microsomes, in addition to 1'-hydroxybufuralol. (unboundmedicine.com)
  • To achieve this, the in vitro metabolism has been studied with liver fractions (S9 or microsomes) from different species and in different induction conditions. (europa.eu)
  • Oxidation of AAI to 8-hydroxyaristolochic acid I (AAIa) in the presence of Cd, Pb, Se, As ions, dibutylphthalate (DBP), butylbenzylphthalate (BBP), bis(2-ethylhexyl)phthalate (DEHP) and OTA by rat liver microsomes was determined by HPLC. (nel.edu)
  • Only OTA, cadmium and selenium ions, and BBP inhibited AAI oxidation by rat liver microsomes. (nel.edu)
  • Trichloroethylene (79016) has been shown to be converted to chloral- hydrate (75876) in the presence of liver microsomes, reduced nicotinamide adenine-dinucleotide-phosphate (53576) (NADPH), and oxygen. (cdc.gov)
  • The metabolism of this and other chlorinated ethylenes in liver microsomes has now been further studied. (cdc.gov)
  • Dichloroacetic-acid, which would be formed via dichloroacetyl-chloride by rearrangement of the epoxide with migration of a hydrogen atom rather than a chlorine- atom, could not be detected as a metabolite of trichloroethylene in liver microsomes. (cdc.gov)
  • The NADPH-dependent formation of trichloroacetic- acid (76039) from tetrachloroethylene in rat liver microsomes has been demonstrated. (cdc.gov)
  • In vitro experiments in human liver microsomes demonstrated that the formation of the hydroxy and 5-O-desmethyl metabolites of esomeprazole is via cytochrome P450 (CYP) 2C19, whereas that of the sulphone metabolite is via CYP3A4. (nih.gov)
  • The formation of both metabolites was inhibited by more than 90% by an antiserum directed against a pregnenolone 16 alpha-carbonitrile-inducible cytochrome P450 (P450PCN1) of rat liver. (aspetjournals.org)
  • The transformation of phenelzine by rat liver microsomes yields 2-phenylacetaldehyde, 2-phenylethanol and ethyl-benzene. (usp.br)
  • Since human liver microsomes formed BCP-NG, we investigated the metabolites of BCP excreted in the urine of a patient after oral administration of BCP (600 mg). (scirp.org)
  • The mutagenic effect of AN was detected only in the presence of liver microsomes and NADPH, confirming the highly toxic effect of products of AN metabolism. (eurekamag.com)
  • Interspecies homology of cytochrome Pー450:toxicological significance of cytochrome Pー450 crossーreactive with antiーrat Pー448ーH antibodies in liver microsomes from dogs,monkeys and humans. (nii.ac.jp)
  • A biochemical comparison of PvdA to two homologues, para-hydroxybenzoate hydroxylase (PHBH from Pseudomonas fluorescens) and flavin-containing monooxygenases (FMOs from Schizosaccharomyces pombe and hog liver microsomes) indicates that PvdA proceeds by a novel reaction mechanism. (ku.edu)
  • The direct spectrophotometric observation of benzo(a)pyrene phenol formation by liver microsomes. (lookformedical.com)
  • Optical spectral repetitive scan analysis during the oxidative metabolism of benzo(a)pyrene by liver microsomal suspensions reveals the time-dependent formation of an intermediate(s) of which the visible spectra resemble those of several benzo(a)pyrene phenols. (lookformedical.com)
  • the rate of formation catalyzed by liver microsomes from phenobarbital-pretreated rats was intermediate. (lookformedical.com)
  • An epoxide hydrase inhibitor, 1,1,1-trichloropropene-2,3-oxide, enhanced phenol formation regardless of the source of liver microsomes, and 7,8-benzoflavone inhibited control and 3-methylcholanthrene-induced microsomal metabolism of benzo(a)pyrene, 7,8-Benzoflavone did not effect benzo(a)pyrene metabolism by liver microsomes from phenobarbital-pretreated rats. (lookformedical.com)
  • Differences in benzo(a)pyrene metabolism between rodent liver microsomes and embryonic cells. (lookformedical.com)
  • Differences in benzo(a)pyrene metabolite pattern have been shown by rodent liver microsomes (Sprague-Dawley) and rodent embryo cells from Syrian hamsters and NIH Swiss mice. (lookformedical.com)
  • Formation in isolated rat liver microsomes and nuclei of benzo(a)pyrene metabolites that bind to DNA. (lookformedical.com)
  • MEC was not produced from NX 211 in the presence of human liver microsomes, suggesting that it is not a product of cytochrome P-450 metabolism. (eur.nl)
  • Our in vitro study indicates that in the brain the content and activity of CYP3A in the mitochondria are higher than those in the microsomes, an observation which is opposite of the pattern reported in the liver. (chapman.edu)
  • In in vitro studies, microsomes were incubated with NADPH in presence and absence of different concentrations of seeds extract. (hindawi.com)
  • The enzyme follows Michaelis-Menten kinetics measuring NADPH oxidation, but substrate inhibition is detected when measuring the formation of hydroxylated product. (ku.edu)
  • To this end, the primary purpose of this study is to develop a CYP3A functional assay in rat brain mitochondria and microsomes to determine the Michaelis-Menten kinetics of the formation of CYP3A-mediated hydroxylated metabolites of midazolam by UPLC-MS/MS. We also aim to analyze the protein levels of CYP3A in the rat brain mitochondria and microsomes by Western blot analysis. (chapman.edu)
  • Thus formation of 4-OH-ALP via hydroxylation is the major route of ALP metabolism. (nih.gov)
  • The formation rate of the hydroxy metabolite from esomeprazole is lower than for (R)-omeprazole, but that of the 2 other metabolites is higher, demonstrating stereoselective metabolism. (nih.gov)
  • The metabolism of midazolam and triazolam to their 1'-hydroxy and 4-hydroxy metabolites was studied in microsomes of 15 human livers. (aspetjournals.org)
  • The local metabolism of CYP3A substrates in the brain microsomes and mitochondria may have significant ramifications for the effectiveness or toxicity of the centrally-acting drugs that are CYP3A substrates. (chapman.edu)
  • L'identification des CYP450 hépatiques humains a été réalisée in vitro à l'aide de microsomes hépatiques humaines et d'enzymes humaines recombinantes. (ata-journal.org)
  • 2019. Formation of (2)- and (2)-8-Prenylnaringenin Glucuronides by Human UDP-Glucuronosyltransferases. . (oregonstate.edu)
  • The formation of the 4- and 6-hydroxylated products was suggested to be catalyzed by P450 1A2, based on the results of correlation with P450 1A2 contents in 60 human samples and inhibition by anti-P450 1A2 and alpha-naphthoflavone. (unboundmedicine.com)
  • CYP2A6 has been shown to be implicated in the formation of quinoline N-oxide by human microsomes. (europa.eu)
  • The same isoenzyme is responsible for the formation of 5,6 -dihydrodiol (in rat and human microsomes). (europa.eu)
  • The formation of 3 -OH quinoline is caused by CYP2E1, and the production of this metabolite is higher in rat than in human microsomes. (europa.eu)
  • The transformation of epoxide to the diol metabolite is catalized by epoxide hydrolase in human microsomes. (europa.eu)
  • Moreover, midazolam hydroxylase activity was immunoprecipitated from solubilized human microsomes with polyclonal antibodies against rat P450PCN1 and the closely related human isozyme P450NF. (aspetjournals.org)
  • The present study investigated whether BCP N-glucuronide (BCP-NG, the primary metabolite of BCP) was produced in mammalian species other than rats, and attempted to identify the UDP-glucuronosyltransferase (UGT) isoform (s) responsible for formation of BCP-NG in humans. (scirp.org)
  • These results suggest that the UGT isoforms responsible for formation of BCP-NG exist in various mammalian species, including humans, and that the UGT 1A family is primarily responsible for BCP N-glucuronide formation in humans. (scirp.org)
  • HEEN exerts its chemopreventive effects by alleviating the xenbiotic enzymes and enhancing the levels of antioxidants and biochemical assays in DENA-induced carcinogenesis by reducing the formation of free radicals. (jcimjournal.com)
  • The metabolite pattern of BP was investigated by using high-pressure liquid chromatography and was found to be similar in nuclei and microsomes from MC-treated rats. (lookformedical.com)
  • In contrast to nuclei from control rats, the nuclear fraction from MC-treated rats showed an increase in bound radioactivity when incubated with a microsome-free supernatant, obtained by incubating microsomes from MC-treated rats with [3H]BP. (lookformedical.com)
  • We used Simulations Pluss ADMET Predictor (TM) and Molecular Discoverys MetaSite (TM) to predict possible metabolite formation. (diva-portal.org)
  • Furthermore, metabolite formation was significantly lower in microsomes of a poor metabolizer. (ata-journal.org)
  • Oxidation of the reduced flavin in the presence of substrate indicates the formation of two transient intermediates, hydroperoxyflavin and hydroxyflavin. (ku.edu)
  • The critical position for the mutagenic / carcinogenic property was confirmed to be in position 2 -3, by a screening carcinogenicity test, mutagenicity test and also by preventing the epoxide formation by substitution (fluoro-, chloro-) of quinoline. (europa.eu)
  • Metabolic formation and inactivation of 1ーnitropyrene oxides and the effect of pyrene administration during nitrogen dioxide exposure on the formation of 1ーnitropyrene metabolites. (nii.ac.jp)
  • Ratios of salicylic acid phenolic to acyl glucuronide formation varied more than 12-fold from 0.5 for UGT1A6 to 6.1 for UGT1A1. (aspetjournals.org)
  • The conjugate formation was primarily catalyzed by heterologously expressed CYP2C19, CYP1A2, and, to a lesser extent, CYP3A4 and CYP3A5. (unboundmedicine.com)
  • The phenobarbital-stimulated formation of endoplasmic membranes is reflected in increased amounts of the various microsomal phospholipid fractions as revealed by thin layer chromatography. (rupress.org)
  • Different concentrations of midazolam were incubated with rat brain microsomes and mitochondria in a side-by-side comparison over a period of 10 minutes. (chapman.edu)
  • As a result, BCP-NG formation (pmol equivalents/min/mg protein) was observed with microsomes expressing hUGT1A1 (142), 1A3 (196), 1A4 (8), 1A7 (8), 1A8 (66), 1A9 (38), 1A10 (9), 2B4 (7) and 2B7 (16). (scirp.org)
  • Even though the relationship of the GSH conjugate to flutamide-induced toxicity is unknown, the results have revealed the formation of a novel, hitherto unknown, GSH adduct of flutamide. (unboundmedicine.com)
  • Formation of AMT, a highly toxic catabolite of AZT, raises a question regarding the role of AMT in the cytotoxic effects of AZT observed in patients. (aspetjournals.org)
  • Unlike dacarbazine, which was not toxic, MTIC, HMMTIC and temozolomide were cytotoxic in the absence of microsomes. (aston.ac.uk)
  • In all species, rates of 4-OH-ALP formation exceeded those of alpha-OH-ALP. (nih.gov)
  • Hereditary UGT deficiencies may allow greater bioactivation to free radical reactive intermediates that can initiate the formation of reactive oxygen species. (aspetjournals.org)
  • Glucosyltransferase activity in calf pancreas microsomes. (wikipedia.org)
  • The subtype-pattern and the activity are significantly changed after an induction of the cells with gamma-Interferon (gamma-IFN) under formation of immuno proteasomes. (hu-berlin.de)
  • When 3-hydroxybenzo(a)pyrene was used as a standard for comparison of activity, the rates of formation of phenols were compared when measured by fluorometric, spectrophotometric, or high-pressure liquid chromatographic analytical techniques. (lookformedical.com)
  • The examination using electron microscopy confirmed the formation of rounded vesicles with distinctive bilayer structure. (springer.com)
  • The formation of MTIC from dacarbazine, HMMTIC and temozolomide was determined by reversed phase high performance liquid chromatography in mixtures incubated under conditions identical to those described before. (aston.ac.uk)
  • Further it has been shown that in cell compartements cytoplasm, microsomes and nucleus of HeLaS3 cells different 20S proteasome subtypes are located. (hu-berlin.de)
  • Phenytoin-initiated micronucleus formation was increased about 4-fold in both +/ j (P = .006) and j/j (P = .009) UGT-deficient cells vs. +/+ UGT-normal cells, providing the first evidence that the bioactivation and oxidative toxicity of phenytoin itself may be avoided by direct N -glucuronidation, which was confirmed by tandem mass spectrometry. (aspetjournals.org)
  • Early lesions show a cluster of macrophages and lymphocytes (predominantly cytotoxic and natural-killer T cells) at the preulcerative base, followed by formation of an ulcer with a neutrophilic base and an erythematous lymphocytic ring. (medscape.com)
  • Consistent with the higher Vmax of the metabolites in the mitochondrial fractions, the Western blot analysis showed higher band intensities related to CYP3A2 in the brain mitochondria, when compared with the brain microsomes. (chapman.edu)
  • The transformation of AN in the MOS led to the formation of highly active products (differing from cyanide products) that caused the damaging effect of this industrial monomer. (eurekamag.com)
  • Enzymatic antioxidants like Superoxide dismutase (SOD), Glutathione peroxidase (GPx) and Catalase (CAT) act primarily as front-line defense to block the formation of free radicals, and especially in the water-soluble cell compartment. (dsm.com)
  • The complex inhibited product formation from MDA and MDMA as well as other P-450 dependent reactions such as benzphetamine demethylation and CO binding. (erowid.org)
  • The method was developed and optimized to determine the Michaelis-Menten kinetics of MDZ 1′- and 4-hydroxylase activities in rat brain microsomes and mitochondria (n=8). (chapman.edu)
  • Therefore, these CYP inhibitions can be responsible for a decrease in AAIa formation. (nel.edu)
  • Formation of these conjugates, catalyzed by UDP-glucuronosyltransferases (UGTs), decreases the amount of pharmacologically active salicylic acid present. (aspetjournals.org)
  • For 4- hydroxymidazolam, brain mitochondria had 2.5-fold higher maximum velocity and 5-fold higher MM constant compared to microsomes. (chapman.edu)