• The cytochrome P450 (P450)-mediated 4-monohydroxylations of the individual enantiomers of the racemic antianginal agent perhexiline (PHX) were investigated in human liver microsomes (HLMs) to identify stereoselective differences in metabolism and to determine the contribution of the polymorphic enzyme CYP2D6 and other P450s to the intrinsic clearance of each enantiomer. (aspetjournals.org)
  • 1970 - Oxidative metabolism of aflatoxin B1 by mammalian liver slices and microsomes. (wikipedia.org)
  • The liver is the primary organ involved in xenobiotic metabolism and is a major target organ for chemicals and drugs. (scialert.net)
  • Although formation of protein-reactive acylating metabolites by phase II metabolism has been well-studied and proposed to be the cause of these toxic side effects, the oxidative bioactivation of MFA has not yet been competely characterized. (unboundmedicine.com)
  • In addition to the major metabolite 3'-OH-methyl-MFA, resulting from the benzylic hydroxylation by CYP2C9, 4'-hydroxy-MFA and 5-hydroxy-MFA were identified as metabolites resulting from oxidative metabolism of both aromatic rings of MFA. (unboundmedicine.com)
  • 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)
  • The LC-BCD system was applied to test how oxidative microsomal metabolism affects the potency of three sEHis. (cdc.gov)
  • A carbon radical is formed during the oxidative metabolism of phenelzine that reacts with the prosthetic heme group of cytochrome P 450 and irreversibly inactivates the enzyme. (usp.br)
  • We conclude that CYP3A4 is the major enzyme involved in the oxidative metabolism of cyclosporin G in human liver. (nih.gov)
  • In vitro metabolism studies in the human liver, microsomes indicate that DXd is metabolised mainly by CYP3A4 via oxidative pathways. (evidentic.com)
  • 8.Belpaire FM, Wijnant P, Temmerman A, Rasmussen BB, Brosen K. The oxidative metabolism of metoprolol in human liver microsomes: inhibition by the selective serotonin reuptake inhibitors. (webmd.com)
  • Our previous work has shown that GBE regulates lipid metabolism and lessens the lipid accumulation in the livers of rats fed a high-fat diet (HFD) or hepatocytes at the transcriptome regulation level. (biomedcentral.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)
  • 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)
  • In vitro studies in liver microsomes and hepatocytes showed that hydroxylation and demethylation reactions by PKCη Purity & Documentation cytochromes P450 (CYP) might be involved in the Phase I metabolism of SGLT2 inhibitors within the liver [10]. (bcrablinhibitor.com)
  • However, the CYP3A4mediated oxidative metabolism of canagliflozin was shown to be negliglible in humans [48]. (bcrablinhibitor.com)
  • Most metabolites of aflatoxin B 1 (AFB 1 ), especially exo-AFB 1 -8,9-epoxide (AFBO), can induce the production of reactive oxygen species (ROS) to vary degrees, causing oxidative stress and liver damage, and ultimately induce liver cancer in humans and animals. (hindawi.com)
  • Similarly, significant increase in Lipid Peroxidation (LPO) level while induced significant decreases in the activities of liver Catalase (CAT) and Glutathione-S-Transferase (GST). (scialert.net)
  • The hepatoprotective effect was observed with d-cis diltiazem but not with l-cis diltiazem, suggesting that diltiazem is stereospecific in protecting against lipid peroxidation using isolated microsomes. (iomcworld.com)
  • When CCl 4 gets into the liver, it acts as a xenobiotic and converted into free radicals CCl 3 and CCl 3 O 2 by the P-450 monooxygenase-dependent microsome system and causes liver damage through membrane lipid peroxidation [ 10 ]. (biomedcentral.com)
  • The results of this study show that, next to phase II metabolites, reactive quinoneimines formed by oxidative bioactivation might also contribute to the idiosyncratic toxicity of MFA. (unboundmedicine.com)
  • After incubation with pig liver microsomes, several metabolites of sEHis were characterized by MS, while their individual potencies were measured by BCD. (cdc.gov)
  • After AFB 1 is absorbed in the intestine, it is converted into various metabolites by many cytochrome oxidase P450 family members (CYP 450 s, CYPs) in the liver. (hindawi.com)
  • Formation in isolated rat liver microsomes and nuclei of benzo(a)pyrene metabolites that bind to DNA. (lookformedical.com)
  • Further studies of the induction of the liver microsomal drug-hydroxylating enzyme system by pretreatment of rats with various drugs are presented. (rupress.org)
  • The phenobarbital-induced increase in the microsomal content of CO-binding pigment and in the activities of TPNH-cytochrome c reductase and the oxidative demethylation of aminopyrine is proportional, within certain limits, to the amount of phenobarbital injected. (rupress.org)
  • NADPH- and GSH-supplemented human liver microsomal incubations of flutamide gave rise to a novel GSH conjugate where GSH moiety was conjugated to the flutamide molecule via the amide nitrogen, resulting in a sulfenamide. (unboundmedicine.com)
  • These results are indicative of a region-specific attack on the carcinogen by the cell monooxygenases which is distinct from the liver attack of microsomal enzymes on benzo(a)pyrene. (lookformedical.com)
  • These compounds also inhibited activities of CYP1A1 and/or CYP2C6/11 catalysing AAI demethylation in rat livers. (nel.edu)
  • 15%) inhibitory effect on S -mephenytoin 4′-hydroxylation by purified CYP2C19 or hepatic microsomes containing CYP2C19. (aspetjournals.org)
  • 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)
  • BaP also induces CYP2C11 protein in rat liver and kidney, but does not increase its enzyme activity measured as testosterone 16α-hydroxylation. (nel.edu)
  • Using the HPLC method, CYP1A1, 2C and 3A specific activities in hepatic microsomes isolated from exposed rats were analyzed. (nel.edu)
  • Whereas exposure to BaP induces expression of CYP1A1 protein and its marker activity (Sudan I oxidation) in liver, kidney and lung of rats, no significant induction of this CYP and its enzyme activity was produced by EE2 and estradiol. (nel.edu)
  • Treatment of BaP in combination with EE2 and/or estradiol decreased the BaP-mediated CYP1A1 induction in liver of exposed rats. (nel.edu)
  • The CYP2C11 protein expression and/or its activity are also increased in liver of rats treated with EE2 and estradiol, but its expression is significantly decreased in lung. (nel.edu)
  • the rate of formation catalyzed by liver microsomes from phenobarbital-pretreated rats was intermediate. (lookformedical.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)
  • Other pharmacological models of liver failure such as acetaminophen can be used, but rats are less sensitive to it`s toxic effects even at higher doses (300-1000 mg/kg IP) [ 9 ]. (biomedcentral.com)
  • AFB 1 has the strong liver toxicity and can reduce production performance, feed utilization [ 3 ], egg production, and immunosuppression in poultry [ 5 ]. (hindawi.com)
  • mice developed severe liver toxicity, which probably tio is less than 1, while in mouse liver the ratio is about contributed to the cause of death. (cdc.gov)
  • 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)
  • 1974. Pesticidal chemicals affecting some energy-linked functions of rat liver mitochondria in vitro . (cdc.gov)
  • In vitro data from studies in human liver microsomes show that Bisoprolol is primarily metabolized via CYPSA4 (-95%) with CYP2D6 having only a minor role. (com.bd)
  • Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride (TG) accumulation in hepatocytes and is commonly associated with dyslipidemia, hypertension, obesity, and hyperglycemia. (biomedcentral.com)
  • Bisoprolol is metabolized via oxidative pathways with no subsequent conjugation. (com.bd)
  • Supplementation with SCC before meals substantially decreased a urinary biomarker of aflatoxin-induced DNA damage in a Chinese population at high risk of liver cancer due to unavoidable, dietary aflatoxin exposure from moldy grains and legumes . (oregonstate.edu)
  • Scientists are hopeful that SCC supplementation will be helpful in decreasing the risk of liver cancer in high-risk populations with unavoidable, dietary aflatoxin exposure. (oregonstate.edu)
  • Polyclonal antibodies were raised to CYP2C9 purified from human liver, and were then back-adsorbed against recombinant CYP2C19 coupled to a solid-phase support. (aspetjournals.org)
  • The cis -, trans1 -, and trans2 -4-monohydroxylation rates of (+)- and (-)-PHX by human liver microsomes from three extensive metabolizers (EMs), two intermediate metabolizers (IMs), and two poor metabolizers (PMs) of CYP2D6 were measured with a high-performance liquid chromatography assay. (aspetjournals.org)
  • Although expression of CYP2C19 in human liver is less than that of CYP2C9, it may play an important role in tolbutamide disposition in subjects expressing either high levels of CYP2C19 or a catalytically deficient CYP2C9 enzyme. (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)
  • Martínez-Cabot A, Messeguer A. Generation of quinoneimine intermediates in the bioactivation of 3-(N-phenylamino)alanine (PAA) by human liver microsomes: a potential link between eosinophilia-myalgia syndrome and toxic oil syndrome. (medscape.com)
  • 1979 - The uncoupling effect of N-(phosphonomethyl) glycine on isolated rat liver mitochondria. (wikipedia.org)
  • The protective actions of ambroxol, rutin, glutathione and harmaline on oxidative damages of various tissue components were compared. (koreascience.kr)
  • This review also summarized some exogenous regulatory substances that can alleviate AFB 1 -induced oxidative stress. (hindawi.com)
  • However, today it is widely used to create animal models of oxidative stress in laboratories [ 8 ]. (biomedcentral.com)
  • TCDD for every step of the mechanism described for 2,3,7,8-TCDD carcinogenesis in humans including receptor binding, gene expression, protein activity changes, cellular replication, oxidative stress, promotion in initiation-promotion studies and complete carcinogenesis in laboratory animals. (who.int)
  • The mechanisms by which they prevent oxidative tissue damages were explored. (koreascience.kr)
  • Ronen N, Livne E, Gross B. Oxidative damage in rat tissue following excessive L-tryptophan and atherogenic diets. (medscape.com)
  • CCL4 is one of the most commonly used agents to induce chronic and acute liver failure in experimental animals at doses of 0.5-2.5 mL/kg. (biomedcentral.com)
  • Whereas only a slight increase in CYP3A protein expression was found by BaP in rat liver, its enzyme activity, testosterone 6β-hydroxyalation, increased significantly in this organ. (nel.edu)
  • 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)
  • Liver metabolomics identifies bile acid profile changes at early stages of alcoholic liver disease in mice. (cuanschutz.edu)
  • 3 μ g/(kg·BW) of AFB 1 can cause significant damage to the DNA of duckling liver cells (Wang et al. (hindawi.com)
  • Ginkgo (Ginkgo biloba) is one of the oldest living tree species and its leaves are among the most extensively studied botanicals in use today. (healthyplace.com)
  • The clinical use of diltiazem has been suggested to be a reasonable approach for combating free radical induced liver damage. (iomcworld.com)
  • 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)
  • Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 are encoded by genes clustered in the 1q23-q25 region. (nih.gov)