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Biomedical subjects

A Takanaka

Publications and source records attributed to A Takanaka.

At least 73 records · Page 4Linked to original sources
PubMed1986

Purification and characterization of a form of cytochrome P-450 with high specificity for aflatoxin B1 from 3-methylcholanthrene-treated hamster liver.

A form of cytochrome P-450 highly active in inducing mutagenicity of aflatoxin B1 was purified to a specific content of 15.1 nmol/mg of protein from 3-methylcholanthrene-treated hamster liver. This species of cytochrome P-450, having its absorption maximum at 448.5 nm in carbon monoxide-complex of reduced form and low spin ferric ion, is of molecular weight of 56,000 and distinctly different in physicochemical and catalytic properties from major forms of cytochrome P-450 purified from phenobarbital- or 3-methylcholanthrene-treated rat liver. In the induction of aflatoxin B1 mutagenicity, this hamster cytochrome P-450 is 50 times more potent than those from rat liver.

Aflatoxin B1↗
PubMed1986

Comparisons of the toxicokinetic parameters in rats determined for low and high dose of gamma-chlordane.

Toxicokinetic parameters of gamma-chlordane (GCD) after oral administration of various doses of radio-labelled GCD (50 micrograms/kg-10 mg/kg) were compared. Absorption of GCD were about 80% in both 0.1 and 1.0 mg/kg groups. Distributions of GCD (50 micrograms/kg and 10 mg/kg) into the liver and kidney were rapid and those into adipose tissues were relatively slow. Concentrations of GCD in adipose tissues became highest at 16 hr after administration and became about 10 times more than those in the liver. The initial concentrations of GCD calculated by two-compartment open model in high dose group (10 mg/kg) were about 200-300 times higher than those in low dose group (50 micrograms/kg). Half lives of GCD in low dose group had a tendency to be a little longer than those in high dose group. This difference seemed to be caused by the accumulation of oxychlordane in low dose group.

Adipose Tissue↗
PubMed1985

Effects of oral contraceptive steroids (norethisterone/mestranol) on the activities of hepatic drug-metabolizing enzymes in iron-deficient anemic rats.

Either oral contraceptive steroid (norethisterone/mestranol; N/M) treatment or iron-deficiency (Fe(-] anemia alone caused an increase in NADPH cytochrome c reductase and in three hepatic microsomal mixed-function oxidase activities in female rats. When N/M treatment and the Fe(-) diet are combined, no further change in hepatic enzyme activity is seen compared with that with either treatment alone.

Aminopyrine↗
PubMed1985

Relation between hepatic microsomal metabolism of N-nitrosamines and cytochrome P-450 species.

Effects of SKF 525A (0.1 mM), metyrapone (0.1 mM), alpha-naphthoflavone (ANF) (0.5 mM) and pyrazole (1.0 mM) on N-nitrosodimethylamine (NDMA), N-nitrosomethylbutylamine (NMBuA) and N-nitrosomethylbenzylamine (NMBeA) metabolism by hepatic microsomes from rats pretreated with inducers were investigated. NDMA demethylation was weakly increased by phenobarbital (PB) treatment. The demethylation was inhibited by SKF 525A and enhanced by metyrapone in non-treated and PB-treated microsomes, and weakly inhibited by ANF in 3-methylcholanthrene(MC)-treated microsomes. NMBuA demethylation was increased by PB treatment and inhibited by SKF 525A in all microsomes. Metyrapone inhibited the demethylation in PB-treated microsomes. NMBuA debutylation was increased by PB and MC treatments, and inhibited by metyrapone in all microsomes. The strongest inhibition by metyrapone was observed in PB-treated microsomes. The debutylation was inhibited by SKF 525A in non-treated and PB-treated microsomes and by ANF in MC-treated microsomes. NMBeA demethylation was decreased by MC treatment and weakly inhibited by SKF 525A in all microsomes. The effects of the inducers and inhibitors on NMBeA debenzylation were almost the same as those on NMBuA debutylation except that the increasing effect of MC was small. Pyrazole was a relatively selective inhibitor of NDMA demethylation. These results suggest the following: NDMA demethylation is catalyzed by PB-induced cytochrome P-450 species (P450-PB) and MC-induced cytochrome P-450 species (P448-MC). But their specific activity is low and the other cytochrome P-450 species demethylate NDMA. NMBuA demethylation is catalyzed by P450-PB. But the specific activity is not high and the other cytochrome P-450 species also demethylate NMBuA. NMBuA debutylation is catalyzed by P450-PB and P448-MC. Almost all of NMBeA demethylation is catalyzed by cytochrome P-450 species other than P450-PB and P448-MC. NMBeA debenzylation is catalyzed by P450-PB and P448-MC, but the specific activity of P448-MC is not high.

Animals↗
PubMed1985

Substrate concentration dependency of N-nitrosodimethylamine and N-nitrosomethylbenzylamine metabolism in rat liver.

Metabolism of N-nitrosodimethylamine (NDMA), a hepatocarcinogen, and N-nitrosomethylbenzylamine (NMBeA), an esophageal carcinogen, was comparatively investigated in rat liver. When these nitrosamines (25 micromole/kg) were administered orally to rats, the clearance of NDMA from the serum and liver was faster than that of NMBeA. The metabolic decomposition of NDMA by rat isolated hepatocytes was slower than that of NMBeA at high concentration (0.5 mM). However, at low concentration (6.7 microM) the metabolic decomposition of NDMA was faster than that of NMBeA. The ratio of NDMA demethylation to NMBeA demethylation and debenzylation by hepatic microsomes also changed depending on nitrosamine concentrations (1 microM to 1 mM), and low concentration of NDMA was demethylated rapidly. These results suggest that NDMA is metabolized to a methylating agent more effectively than NMBeA in liver, when carcinogenic doses of nitrosamines are administered.

Animals↗
PubMed1984

Nature of N-nitrosodimethylamine demethylase in hepatic microsomes of rats.

The nature of enzymes involved in demethylation of N-nitrosodimethylamine (NDMA) was investigated in hepatic microsomes of rats. Compared to the other cytochrome P-450-dependent enzymes. NDMA demethylase had anomalous properties as reported in the literature. However, kinetic analysis suggested a qualitative change in NDMA demethylase induced by phenobarbital (PB) and 3-methylcholanthrene (MC) pretreatment. The inhibition of demethylase by alpha-naphthoflavone in MC-treated microsomes also suggested that cytochrome P-450 species induced by MC are active in demethylating NDMA. The enhancement of NDMA demethylase activity by metyrapone in PB-treated microsomes was greater than in non-treated ones, and was not observed in MC-treated ones. The result is almost the same as in acetanilide hydroxylation, depending on cytochrome P-450. Pyrazole, tranylcypromine, and aminoacetonitrile, which are selective inhibitors of NDMA demethylation, interacted with cytochrome P-450 species to produce type-II spectra, and typical type-II compounds (aniline, imidazole, and nicotinamide) were inhibitors of the NDMA demethylation. Tranylcypromine irreversibly inhibited microsomal monoamine oxidase [EC 1.4.3.4], but not NDMA demethylase. Semicarbazide (a copper- and pyridoxal-containing amine oxidase [EC 1.4.3.6] inhibitor) had no effect on demethylation. From these results it is concluded that NDMA demethylation depends only on cytochrome P-450-dependent monooxygenases.

Aminoacetonitrile↗
PubMed1984

Comparison of hepatic drug-metabolizing enzymes induced by 3-methylcholanthrene and phenobarbital between pre- and postnatal rats.

Effects of 3-methylcholanthrene (3MC) and phenobarbital (PB) on the hepatic drug-metabolizing enzyme system in fetal liver of rats were investigated. Intraperitoneal administration of 3MC (25 mg/kg, 72 and 48 hr before death) to pregnant rats significantly increased hexobarbital (HB) and aminopyrine (AM)-metabolizing activities in fetuses on the 21st day of gestation to 148.0 and 150.6% of control fetuses, respectively. In contrast, HB and AM-metabolizing activities in 4-day-old neonates and mothers were decreased by administration of 3MC on the 21st day of gestation. Benzo[a]pyrene (BP)-metabolizing activity, NADPH-cytochrome c reductase activity, and cytochrome P-450 content in 3MC-treated fetuses were significantly increased to 2143.6, 137.6, and 323.8% of the control, respectively. Following 3MC administration, the maximum absorption of the cytochrome P-450-CO difference spectra in liver microsomes of fetuses was observed at 449-450 nm. The induction profile following 3MC administration in the fetal livers was different from that in the neonatal and the maternal livers. On the other hand, intraperitoneal administration of PB (60 mg/kg, 72, 48, and 24 hr before death) significantly increased HB, AM, and BP-metabolizing activities in fetal livers to 263.7, 231.0, and 151.2% of the respective controls. The profile induced by PB in the fetal livers was similar to that in maternal livers. These results suggest that HB and AM-metabolizing enzymes in fetal livers treated with 3MC or PB possess the capacity to be induced, and the responsiveness of the drug-metabolizing enzyme system to 3MC during the prenatal stage may differ from the postnatal stage.

Aminopyrine↗
PubMed1984

Renal aminopyrine demethylation in several species determined by a sensitive radiometric method.

Renal microsomal aminopyrine demethylation activities of several species were measured by a sensitive radiometric method using [dimethylamino-14C-]aminopyrine as a substrate and 2,4-dinitrophenylhydrazine as a trapping agent for the formaldehyde formed. The activity was highest in hamsters (0.75 nmol min-1 mg-1 protein) and that in rabbits, rats, mice, and guinea-pigs was 19.7, 7.0, 4.5 and 3.7%, respectively, of the hamster values. These species differences did not correlate with species differences in cytochrome P-450 content or in NADPH cytochrome c reductase activity. Aminopyrine demethylation activities in sliced renal tissues of several species were also compared. This activity was also found highest in hamsters (0.54 nmol min-1 g-1 wet tissue) and the activities in rabbits, rats, and guinea-pigs were 9.2, 1.8 and 2.5%, respectively, of the hamster values.

Aminopyrine↗
PubMed1984

Renal microsomal N-nitrosodimethylamine demethylase determined by a sensitive radiometric method.

Renal microsomal N-nitrosodimethylamine (NDMA) N-demethylation was measured in several species by a sensitive radiometric method using [14C]NDMA as a substrate and 2,4-dinitrophenylhydrazine (DNPH) as a trapping agent of the [14C]formaldehyde formed. The activities were the highest in mice and lowest in hamsters. The activities in rats could not be detected. Among several strains of mice studied the DDY strain was the highest in its activities. Although nicotinamide adenine dinucleotide supported NDMA demethylation by about 32% of nicotinamide adenine dinucleotide phosphate in kidney and only 16% in liver, other properties (pH profiles, km values, and effects of inhibitors) exhibited almost similar results in liver as compared to kidney.

Animals↗
PubMed1983

The heterogeneity of arylhydrocarbon hydroxylase in fetal liver microsomes of rats.

The characteristic of arylhydrocarbon hydroxylase system in fetal liver microsomes of rat was investigated. NADH-synergistic effect on NADPH-dependent arylhydrocarbon hydroxylase was observed in fetal liver microsomes of rat but not in maternal liver microsomes. NADH-synergistic effect decreased in parallel with the decrease of the ratio of cytochrome b5/cytochrome P-450 in liver microsomes. The cytochrome P-450 in arylhydrocarbon hydroxylase system in fetal liver microsomes of rat seemed to be different from that in offspring liver microsomes in respect of its dependency on cytochrome b5 system for its maximum activity.

4-Chloromercuribenzenesulfonate↗
PubMed1983

Simultaneous determination of aminopyrine hydroxylation and aminopyrine N-demethylation in liver microsomes by high-performance liquid chromatography.

Aminopyrine and its metabolites, including 3-hydroxymethyl-2-methyl-4-dimethylamino-1-phenyl-3-pyrazoline-5-one which is a hydroxylated metabolite of aminopyrine, were separated on a reversed-phase (C8) Radial-Pak column using a mobile phase of methanol-triethylamine-water (30:1:69) adjusted to pH 5.40 with acetic acid. Detection of the peak was performed by an ultraviolet detector at 254 nm. By the rapid and simple method, aminopyrine hydroxylation as well as aminopyrine N-demethylation in liver microsomes can be examined simultaneously.

Aminopyrine↗
PubMed1983

Cytotoxic effects of methylnitrosourea on developing brain.

The effect of methylnitrosourea (MNU) on cerebellar and cerebral DNA, RNA, protein, lysosomal enzymes (acid DNase, RNase, phosphatase, and beta-glucuronidase), and 2',3'-cyclic nucleotide 3'-phosphohydrolase (2',3'-CNPase) activities was studied in rats from birth through 12 days of age. Subcutaneous injection of MNU in a dose of 0.625 mmol/kg caused a suppression of increase in weights and content of DNA, RNA, and protein of cerebellum, but no changes in those of the cerebrum or in body weight. Ratios of protein and RNA to DNA were substantially elevated by MNU in the cerebellum but not in the cerebrum. Acid DNase and acid RNase activities of MNU-treated rats were significantly elevated beyond the increase of these activities in controls in the cerebellum, but no change in these activities by MNU was observed in the cerebrum. A slight elevation in acid phosphatase activity was observed in the cerebellum but not in the cerebrum after MNU pretreatment. Beta-glucuronidase and 2',3'-CNPase activities were not changed in the cerebellum or in the cerebrum. These results suggest that in the developing brain, especially in the cerebellum at the mitotic stage, MNU caused cell damage and inhibited cell mitosis.

Acid Phosphatase↗