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Biomedical subjects

S Iguchi

Publications and source records attributed to S Iguchi.

At least 73 records · Page 4Linked to original sources
PubMed1983

Synthesis and 5-lipoxygenase inhibitory activities of eicosanoid compounds.

Ten eicosanoid compounds (3, 6, 9, 11, 12, 15, 18, 21, 23, and 25), methyl (6E,8Z,11Z,14Z)-5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE, 10), leukotriene A4 (26), and (5S,6E,8E,10E,12RS,14E)-5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid (5,12-diHETE, 27) were prepared and their inhibitory activities against the 5-lipoxygenase from guinea pig polymorphonuclear leukocytes (PMNL) were tested. 5,6-Methanoleukotriene A4 (18) was especially a potent and specific inhibitor of the 5-lipoxygenase without inhibiting the cyclooxygenase and the 12-lipoxygenase. Leukotriene A4, 5-HETE, and 5,12-diHETE also have inhibitory activities against the 5-lipoxygenase at micromolar concentrations, which can regulate the formation of slow-reacting substance of anaphylaxis intracellulary.

Animals↗
PubMed1983

Effect of environmental temperature on the content of cytochrome P-450 and activity of NADPH-cytochrome C reductase in rats.

The effect of environmental temperature on the content of cytochrome P-450 or the activity of nicotinamide adenine dinucleotide phosphate-cytochrome c (NADPH-cytochrome c) reductase was examined by using microsomes prepared from rats kept at 30 degrees C or 15 degrees C for 14 d. The warm exposure (30 degrees C for 14 d) resulted in a significant reduction of the activity of NADPH-cytochrome c reductase though the content of cytochrome P-450 was not changed. The level of thyroxine and 3,3',5-triiodothyronine was reduced by the warm exposure. From the present observation, it was suggested that the effect of environmental temperature on the metabolism of drugs was due to the activity of NADPH-cytochrome c reductase mediated by the level of thyroid hormone.

Animals↗
PubMed1983

Brain distribution of hydrazine and its GABA elevating effect in rats.

After the intravenous administration of isoniazid (INH; 0.37 mmol/kg) or hydrazine (Hz; 0.16 mmol/kg), the minor metabolite of INH, gamma-aminobutyric acid (GABA) and Hz were measured by means of gas chromatograph-mass spectrometer (GC-MS) using deuterium labeled GABA (d2-GABA) and nitrogen fifteen labeled Hz (15N-Hz) as internal standards. In both cases, we successfully detected Hz and GABA in the brain. The brain GABA elevating effect of Hz was much higher than that of INH in spite of low dose.

4-Aminobutyrate Transaminase↗
PubMed1983

Influence of phenobarbital and 3-methylcholanthrene on the metabolism of aminopyrine in isolated hepatocyte system.

The effect of phenobarbital (PB) and 3-methylcholanthrene (3-MC) on the metabolic behavior of aminopyrine (AM) was studied using an isolated hepatocyte system prepared from male Wistar rats. The formation of 4-formylaminoantipyrine (FAA) was increased after pretreatment with PB, but not 3-MC. However, the total amounts of AM and its main metabolites recovered from hepatocyte system after the incubation for 30 min were considerably reduced both by PB and 3-MC-pretreatment. Furthermore, when using 4-monomethylaminoantipyrine (MAA), the first metabolite of AM, as a substrate, 3-MC-pretreatment resulted in a more significant decrease in the total amounts of MAA and its further metabolites recovered than did PB. Present observation suggests the participation of cytochrome P-448 as well as cytochrome P-450 in the metabolism of AM.

Aminopyrine↗
PubMed1983

Further investigations on brain distribution of hydrazine and its gamma-aminobutyric acid elevating effect in rats.

Perry's hypothesis that hydrazine (Hz) derived from isoniazid (INH) treatment plays an important role in the elevation of brain gamma-aminobutyric acid (GABA) levels was reexamined by measuring Hz and GABA levels in the brain after the treatment with 50 mg/kg of INH or different doses of Hz. The treatment with 50 mg/kg of INH to rats resulted in the elevation of GABA levels in rat whole brain. The maximum levels of GABA increased about twice at 4 h from 2.06 +/- 0.4 mumol/g wet wt. in the control group to 3.61 +/- 0.4 mumol/g wet wt. in INH treated group. In this case, brain levels of Hz ranged from 25.6 to 80.8 ng/g wet wt. within 10 h. On the other hand, Hz levels after the treatment with 0.5 mg/kg of Hz were about five times higher than those after INH treatment. However, 0.5 mg/kg of Hz treatment did not increase brain GABA levels at all. Perry's hypothesis was denied by the fact that brain Hz levels after INH treatment were too low to elevate brain GABA levels.

Animals↗
PubMed1982

Studies of isoniazid metabolism in isolated rat hepatocytes by mass fragmentography.

Isoniazid metabolism in isolated rat hepatocytes was studied by mass fragmentography using single ion monitoring. Isoniazid and its metabolites were determined as the trimethylsilylated derivatives of acetylisoniazid and diacetylhydrazine and of the benzaldehyde hydrazones of isoniazid and acetylhydrazine. Deuterated analogues served as internal standards. Hydrazine was quantitated as benzalazine using 15N-labeled hydrazine as an internal standard. The method is well suited for the microanalysis of isoniazid metabolism, from which it was clarified that the greater part of hydrazine, a hazardous metabolite of isoniazid, was formed through the direct hydrolysis of isoniazid itself as expected.

Acetylation↗
PubMed1982

Isoniazid disposition, comparison of isoniazid phenotyping methods in and acetylator distribution of Japanese patients with idiopathic systemic lupus erythematosus and control subjects.

1 Plasma levels of isoniazid (INH) and acetyl INH in plasma were measured with a spectrofluorometric method, and INH and its metabolites (acetyl INH, mono-acetylhydrazine, diacetylhydrazine and free hydrazine) excreted in urine were measured with a gas chromatography-mass spectrometry, respectively, after an oral dose of INH 10 mg/kg in 19 Japanese patients with idiopathic systemic lupus erythematosus (SLE) and in the same number of healthy controls. 2 When phenotyped according to various methods previously reported, 16 to 18 of the SLE and 17 to 19 of the control group were rapid acetylators. Regardless of the phenotyping methods applied, the distribution of acetylator phenotype of SLE patients was not significantly different from the control group or from the data previously reported among normal Japanese population. 3 By phenotyping our subjects with an INH T 1/2 of 110 min or less as rapid acetylators, and more slow acetylators, 3 of SLE patients and 2 of the controls were slow, while the remainder were all rapid. When this antimode was used, the mean apparent kinetic variables of INH and acetyl INH estimated from the plasma concentration-time data and the mean values for the 24-h urinary amount of INH and its metabolites, except for monoacetylhydrazine (P less than 0.05), did not significantly differ between the rapid acetylators of SLE and control groups. 4 The distribution of INH T 1/2, acetyl INH to INH ratios in plasma and urine, values in urine for log10 (diacetylhydrazine to monoacetylhydrazine) and for diacetylhydrazine to INH or acetyl INH was similar between the two groups except for one patient who was definitely classified as a slow acetylator regardless of whichever phenotyping methods were used. The excretory patterns of hydrazine compounds reflect, in general, the inactivating ability of INH in each individual. 5 The data suggest that phenotyping by using plasma samples is, in general, better than by using urine samples. The plasma T 1/2 alone is the most satisfactory criterion. 6 We conclude that neither INH disposition nor phenotype distribution assessed by the reported methods using INH as the test compound are altered in idiopathic SLE, and that a search for racial and/or geographical factor(s) likely to result in autoimmune disease may give a clue to the pathogenesis in addition to further exploration for the possible interrelation between idiopathic SLE and genetic slow acetylation.

Acetylation↗