Search results for "Microsome"
showing 10 items of 262 documents
Significance of Various Enzymes in the Control of Mutagenic and Carcinogenic Metabolites Derived from Aromatic Structures
1984
One important early contribution to the control of chemical carcinogenesis is provided by the enzyme pattern responsible for the generation and disposition of reactive metabolites. Especially well studied is the important group of enzymes responsible for the control of reactive epoxides. Many natural as well as man-made foreign compounds, including Pharmaceuticals, possess olefinic or aromatic double bonds. Such compounds can be transformed to epoxides by microsomal monooxygenases present in very many mammalian organs. By virtue of their electrophilic reactivity such epoxides may spontaneously react with nucleophilic centers in the cell and thus covalently bind to DNA, RNA, and protein. Su…
The capacity of liver microsomes to form benzo[a]pyrene-diolepoxide-DNA adducts and induction of cytochrome P450 1A in feral fish exposed to pulp mil…
1996
An investigation was made of cytochrome P4501A (CYP1A) induction, determined by the activity of EROD (7-ethoxyresorufin O-deethylase), and formation of benzo[a]pyrene-diolepoxide-DNA (BPDE-DNA) adducts, measured by synchronous fluorescence spectrophotometry, in liver microsomes of perch (Perca fluviatilis), bream (Abramis brama), and roach (Rutilus rutilus). Fish were collected from the southern part of Lake Saimaa (Finland), an area polluted by effluents from the pulp and paper industry. In addition, two conjugation enzymes (UDP-glucuronosyltransferase and glutathione S-transferase) were determined. Overall, when compared to an upstream reference, EROD activity was higher in fish at waters…
Inhibitory Effects of Various Extracts of Argentine Plant Species on Free-radical-mediated Reactions and Human Neutrophil Functions
1996
Extracts of Argentine plant species used in folk medicine were evaluated for their antioxidant properties and ability to influence human neutrophil functions, including superoxide anion release and degranulation. The infusion and methanol extract of Achyrocline flaccida, and the infusion of Pterocaulon polystachium exhibited chain-breaking antioxidant activity in Fe 2+ /ascorbate-induced lipid peroxidation of rat liver microsomal fractions and scavenged peroxyl radicals in an aqueous assay system. Nevertheless their superoxide scavenging ability was lower. The dichloromethane extracts of Phyllanthus sellowianus, Achyrocline flaccida, Gamochaeta simplicicaulis, Pterocaulon polystachium and E…
Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes
2017
Pinostrobin (PI, 5-hydroxy-7-methoxyflavanone) is a natural flavonoid known for its rich pharmacological activities. The objective of this study was to identify the human liver cytochrome P450 (CYP450) isoenzymes involved in the metabolism of PI. A single hydoxylated metabolite was obtained from PI after an incubation with pooled human liver microsomes (HLMs). The relative contributions of different CYP450s were evaluated using CYP450-selective inhibitors in HLMs and recombinant human CYP450 enzymes, and the results revealed the major involvement of CYP1A2, CYP2C9 and CYP2E1 in PI metabolism. We also evaluated the ability of PI to inhibit and induce human cytochrome P450 enzymes in vitro. H…
Die Reversibilität der Wirkung von Digitoxin, Strophanthidin und Strophanthidin-3-bromazetat am Papillarmuskel und einer mikrosomalen Na+-K+-aktivier…
1969
The reversibility of the inhibitory action of strophanthidin, strophanthidin-3-bromoacetate, and digitoxin on the Na+-K+-ATPase activity (microsomal fraction, guinea-pig brain) was compared with the rate of decline of their positive inotropic effects (papillary muscle, guinea-pig heart) after exposure to drug-free solution. The actions of strophanthidin and digitoxin were easily reduced on both systems. Strophanthidin-3-bromoacetate, however, was found to have an irreversible blocking effect on the transport ATPase, whereas its inotropic action could be rapidly abolished.
Incorporation of S35-Methionine in the microsomes and soluble proteins during the early development of the sea urchin egg
1960
Nelle uova diParacentrotus lividus gia pochi minuti dopo la fecondazione si inizia una attiva incorporazione di metionina-S35 nei microsomi e nelle proteine solubili. Si avanza l'ipotesi che cio possa indicare l'iniziarsi molto precoce della sintesi di una o piu proteine.
Experiments on the metyrapone reducing microsomal enzyme system.
1970
The formation of reduced metyrapone [2-methyl-1.2-bis-(3-pyridyl)-1-propanol] from metyrapone [2-methyl-1.2-bis-(3-pyridyl)-1-propanone] in the liver has been studied. Reduced metyrapone appeared as the main metabolite of metyrapone in the isolated perfused rat liver. Experiments on the intracellular distribution of the metyrapone reducing activity revealed that metyrapone reductase is mainly localized in the microsomal fraction. In the 105,000 × g supernatant only a little activity was found.
�ber die Wirkung von Metyrapon auf den mikrosomalen Arzneimittelabbau
1967
The inhibitor of adrenal steroid-11-β-hydroxylation, Metyrapone (SU 4885), also decreases the rate of drug hydroxylation reactions, both in vitro and in vivo. The follwing oxidative microsomal reactions were studied: O-demethylation of p-nitroanisole, N-demethylation of amidopyrine, and ring hydroxylation of acetanilide. In all three cases Metyrapone inhibits the formation of the reaction products. The inhibitor concentrations required for reduction of the initial reaction rates to one half are 7.5 · 10−4 M, 5 · 10−4m and 20 · 10−4 M, respectively. Steroid C-11-β-hydroxylation is reduced to one half by 2.5 · 10−4 M Metyrapone.
Strategies and Molecular Probes to Investigate the Role of Cytochrome P450 in Drug Metabolism
2003
Drug metabolism is the major determinant of drug clearance and, because of polymorphic or inducible expression of drug-metabolising cytochrome P450s (CYPs), is the factor most frequently responsible for interindividual differences in pharmacokinetics. A number of well characterised CYP substrates and inhibitors have been identified that allow precise measurements of individual CYP isoforms. Their use, alone or in combination, facilitates the phenotype characterisation of hepatocytes in vitro and in vivo. Two procedures are used for in vitro investigation of the metabolic profile of a drug: incubation with microsomes and incubation with metabolically competent cells. The major limitation of …
Mangifera indica L. Extract and Mangiferin Modulate Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes in Primary Cultures of Human Hepatocytes
2012
The aqueous stem bark extract of Mangifera indica L. (MSBE) has been reported to have antioxidant, anti-inflammatory and analgesic properties. In previous studies, we showed that MSBE and mangiferin, its main component, lower the activity of some cytochrome P-450 (P450) enzymes in rat hepatocytes and human liver microsomes. In the present study, the effects of MSBE and mangiferin on several P450 enzymes and UDP-glucuronosyltransferases (UGTs) in human-cultured hepatocytes have been examined. After hepatocytes underwent a 48-h treatment with sub-cytotoxic concentrations of the products (50-250 µg/mL), a concentration-dependent decrease of the activity of the five P450 enzymes measured (CYP1A…