Search results for "Metyrapone"

Unexpected adverse effect of metyrapone: A case report

2018

Enzymic control of irreversible binding of metabolically activated benzo(a)pyrene in perfused rat liver by monooxygenase activity.

1977

Addition of [3H]-benzo(a)pyrene to the perfusion medium of isolated rat livers results in irreversible binding of radioactivity to DNA, RNA and protein. Binding to DNA accounted for about 0.1% of the total radioactivity which was bound in livers from animals treated with oil or saline and was increased by a factor of 3–5 after pretreatment of the animals with β-naphthoflavone or with phenobarbital. When the inhibitiors of monooygenase activity, α-naphthoflavone or metyrapone, were present in the perfusion medium, irreversible binding was reduced in livers from both β-naphthoflavone- and phenobarbital-pretreated animals, irrespective of the inhibitor used.

Metabolism of metyrapone by a soluble enzyme system in rat liver.

1970

The formation of a metabolite of metyrapone by an oxygen sensitive soluble enzyme system in rat liver 105,000×g supernatant has been demonstrated. Enzyme activity requires the intact keto function of metyrapone.

Morphological and biochemical effects of glucocorticoids in chick embryo hepatocytes during development

1988

Abstract The administration in ovo of hydrocortisone-21-phosphate caused, in chick embryo liver, a reduction of the number of hepatocytes which can be isolated from 1 mg dry weight of liver and a marked increase of their size. Moreover, the treatment diminished the incorporation of thymidine into acid-insoluble fraction in these cells whilst it augmented the content of protein, RNA, DNA and the level of thymidine kinase/cell. These effects were highest at 8–10 days, then declined with the age, disappearing after 18th day of incubation. Similar effects were obtained by injecting other glucocorticoids or ACTH. Combined treatment with metopirone abolished the effects found with ACTH, but did n…

Zur Wirkung von Angiotensin II auf die Nebennierenrinde bei Blockade der 11-β-Hydroxylierung

1964

Tierexperimentell wird der von uns beobachtete Bremseffekt des Angiotensin II auf die unter Metopiron erhohte ACTH-Ausschuttung der Hypophyse untersucht.

Effect of serotonin uptake inhibition by zimelidine on hypothalamic-pituitary-adrenal activity

1983

Plasma ACTH levels after oral ingestion of 2 g metyrapone at 24.00 hours in six healthy subjects were higher after pretreatment with zimelidine (300 mg) in comparison to placebo. Since zimelidine is a relatively selective serotonin reuptake inhibitor its action on hypothalamic-pituitary-adrenal (HPA) activity suggests that serotonin is a potent stimulator of ACTH release. The ratio of cortisol to 11-deoxycortisol was taken as a measure of 11-hydroxylase activity, which indicates biological activity of secreted ACTH. These cortisol/11-deoxycortisol ratios were significantly increased after zimelidine treatment, when compared to placebo. Both the ACTH response and the cortisol/11-deoxycortiso…

Differential inhibition of biphenyl hydroxylation in perfused rat liver

1978

A differential inhibition of biphenyl hydroxylation by alpha-naphthoflavone and metyrapone was observed in isolated perfused rat liver. alpha-Naphthoflavone inhibited 2- and 4-hydroxylation in livers from beta-naphthoflavone-pretreated animals but had no effect on both reactions in livers from phenobarbital-pretreated animals. Metyrapone inhibited 2- and 4-hydroxylation in phenobarbital-stimulated livers, but only insignificant inhibition of 2-hydroxylation and a slight enhancement of 4-hydroxylation by metyrapone was observed in beta-naphthoflavone-stimulated livers. Conjugation of 2-hydroxybiphenyl and 4-hydroxybiphenyl by isolated perfused livers was also studied. 4-Hydroxybiphenyl prefe…

Action of metyrapone on the redox state of free nicotinamide-adenine dinucleotide and on oxygen consumption of perfused rat livers and isolated mitoc…

1971

Metyrapone [2-methyl-1,2-bis-(3-pyridyl)-1-propanone] in a concentration of 5 mM increased the lactate/pyruvate ratio and theΒ-hydroxybutyrate/ acetoacetate ratio in the perfusion fluid of the isolated rat liver by a factor of 6 indicating a considerable shift in the ratio of free [NAD]/[NADH] in both the cytoplasmic and the mitochondrial compartment. Oxygen uptake of the isolated liver was decreased to about one half. The onset of the inhibitory effect on the respiration of the isolated organ was immediate. The inhibition lasted for at least 1 h.

The cytotoxicity of mitomycin C and Adriamycin in genetically engineered V79 cell lines and freshly isolated rat hepatocytes

1995

The objective of the present study was to investigate the cytotoxicity of Adriamycin (ADR) and mitomycin C (MMC) in tumor and non-tumor cells with respect to the role of cytochrome P450 (P450). Therefore, genetically engineered V79 Chinese hamster fibroblasts expressing only single enzymes of P450 were used. SD1 and XEM2 cells expressed rat P450IIB1 and P450IA1, respectively, whereas the V79 parental cells contained no detectable P450 levels. The cytotoxicity of ADR and MMC in the V79 cell system was compared with that in freshly isolated hepatocytes from phenobarbital (PB-hepatocytes)- and beta-naphthoflavone (beta NF-hepatocytes)-induced rats. Following 24 h of exposure to ADR equal cytot…

Kinetic experiments on the binding of metyrapone to liver microsomes

1969

Kinetic experiments on the inhibition of oxidative microsomal O- and N-demethylations by metyrapone (2-methyl-1, 2-bis(3-pyridyl)-l-propanone, Su 4885) were carried out using mouse liver microsomes as the enzyme source. The model substrates were p-nitroanisole and N-monomethyl-p-nitroaniline. It was shown that the inhibition is competitive. The K i for metyrapone is 0.42 × 10−4 M and for the reduced metabolite of metyrapone 1.15×10−4 M. Their spectral dissooiation constants as determined from difference spectra have almost the same values. From this it is concluded that the degree of inhibition is correlated to the amount of metyrapone bound to cytochrome P-450. Metyrapone does not seem to …