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Biomedical subjects

H Kitagawa

Publications and source records attributed to H Kitagawa.

At least 523 records · Page 29Linked to original sources

Effect of successive administration of zopiclone, a new class of minor tranquillizer, on mouse liver microsomal mono-oxygenase system.

Oral administration of zopiclone to mice (10 mg/kg daily) for 14 days had no significant effect on body weight, liver weight, hepatic microsomal protein or cytochrome P-450 contents but produced significant increases in the activities of NADPH-cytochrome c reductase, NADH-ferricyanide reductase, aniline hydroxylation and aminopyrine N-demethylation.

Aminopyrine N-Demethylase↗

Effect of steroidal sex hormones on the sex-related differences in the hepatic activities of gamma-glutamyltranspeptidase, glutathione S-transferase and glutathione peroxidase in rats.

The activities of gamma-glutamyltranspeptidase (gamma-GTP) and glutathione peroxidase (GSH-Px) were higher in female than in male rat liver. Glutathione S-transferase (GST) activities were conversely higher in males than females. Estradiol administration to castrated rats enhanced the gamma-GTP activity. Castration produced a significant increase in GSH-Px activities which was reduced to the control level by subsequent testosterone treatment. Ovariectomized rats had markedly increased the GST activity. These results suggest that GSH-related enzymes studied here may be subject to modulation by androgenic and estrogenic influences.

Animals↗

Effects of a single administration of 6-aminonicotinamide on hepatic microsomal drug metabolism in rats.

Pretreatment of rats with 6-aminonicotinamide (6-AN) induced a significant increase in aminopyrine (AM) N-demethylation and hexobarbital (HX) hydroxylation in rats. In this study, the concentrations of AM, 4-monomethylaminoantipyrine (MAA), aminoantipyrine (AA) and further metabolites were measured by using the GC/MS method. The increase in AM N-demethylation induced by 6-AN treatment was confirmed by measuring the area under the plasma concentration-time curve (AUC) for AM, MAA and AA in rats after AM administration. Of the first two steps of AM metabolism mediated by cytochrome P-450-coupled monooxygenase, the second step (from MAA to MA) was found to be more affected by 6-AN than the first one (from AM to MAA).

6-Aminonicotinamide↗

Host-mediated inhibition of rat bladder cancer growth by cyclophosphamide and purine salvage pathway-related enzyme activity of lymphocytes.

In ACI/N rats pretreated with cyclophosphamide (CY) growth of the bladder cancer, BC-47, and adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities in lymphocytes were investigated to clarify the possible antitumor effect via the immune system of the chemotherapeutic agent. A single dose of 50 mg/kg of CY with the tumor implantation 3 days later gave rise to tumor regression following temporary progression around day 15 and significant increase of peripheral lymphocytes with higher PNP activity on days 7 to 10 of the tumor implantation. In the thymus such lymphocytes increased 3 days earlier. The antitumor effect was not demonstrated in athymic nude mice. In the light of the results and elimination of suppressor T precursors by CY, it was postulated that T lymphocytes with higher PNP activity act as effector cells in the antitumor immunity whereas suppressor T precursors belong to the cell population with lower PNP activity.

Adenosine Deaminase↗

Teratogenicity of aspirin and its metabolite, salicylic acid, in cultured rat embryos.

Rat embryos were exposed to aspirin or its metabolite, salicylic acid in culture. In these embryos acute reduction of heart beat was observed during 4 hours of administration compared to that in non-treated one. Protein contents and crown-rump length of cultured embryos were significantly decreased in aspirin-treated group, but were not so decreased in salicylic acid-treated one. The predominant defects of the embryos exposed to aspirin were edematous facial malformations and abnormality of tail. On the other hand, facial anomalies such as cleft lip and curly tail were observed in the embryos cultured with salicylic acid. Anomalies induced by aspirin were systemic, while salicylic acid induced localized malformations. These results might be due to the differences between aspirin and its metabolite, salicylic acid in their teratogenicity.

Abnormalities, Drug-Induced↗

Gonadal hormone-induced changes in hepatic microsomal carboxylesterase in rats.

Hepatic microsomal carboxylesterase (E.C. 3.1.1.1) from rat liver microsomes showed a different capacity for the hydrolysis of various substrates. In castrated male rats, the enzyme activities towards p-nitrophenylacetate and malathion were decreased. When testosterone propionate was administered to castrated male rats, the activities of p-nitrophenylacetate and malathion hydrolases were reversely increased. However, in ovariectomized female rats, the carboxylesterase activities showed substrate-dependent changes, i.e., increase in p-nitrophenylacetate and malathion hydrolases and decrease in acetanilide and isocarboxazid hydrolases. When estradiol benzoate was administered to ovariectomized female rats, the activities of p-nitrophenyl-acetate and malathion hydrolases were decreased; and acetanilide and isocarboxazid hydrolases were increased. These results suggest that hepatic microsomal carboxylesterases may be, at least in part, regulated by gonadal hormones which exert different effects on the several isozymes of carboxylesterases.

Acetanilides↗

[Effect of cis-diammine dichloroplatinum, vindesine sulfate combination chemotherapy for advanced esophageal carcinoma].

Eleven patients with advanced squamous cell carcinoma of the esophagus were treated with a two-drug combination of cis-diammine dichloroplatinum and vindesine sulfate at Saitama Cancer Center between July 1982 and September 1983. Median age was 71 years old (range: 47-48) and 8 patients were greater than 70 years old. Median performance status was 3 (range: 1-4) by Koyama -Saito Criteria. Male female ratio was 6:5. Of the 11 patents, three obtained partial response (27.3%), lasting 8 weeks, 20 weeks+, and 42 weeks-, respectively, and three patients had minor response (27.3%). The major toxic effects including myelosuppression, nausea and vomiting were in general manageable.

Aged↗

Effect of acetone on aniline hydroxylation by a reconstituted system.

Acetone stimulated NADPH-dependent aniline hydroxylation catalysed by cytochrome P-450 purified from phenobarbital-treated rats. No activation by acetone occurred in a reconstituted system containing cytochrome P-448 purified from 3-methylcholanthrene-treated rats. Cumene hydroperoxide-supported aniline hydroxylation catalysed by cytochrome P-450 was not increased by the addition of acetone at the concentration which stimulated NADPH-dependent aniline hydroxylation in the reconstituted system. The NADPH-dependent cytochrome P-450 reduction was stimulated by acetone in the presence or absence of aniline. On the other hand, acetone did not exhibit any stimulatory effect on NADPH-dependent reduction of cytochrome P-448. The stimulatory effect of acetone on aniline hydroxylation was decreased with increasing pH of the reaction media. Furthermore, in the system containing cytochrome P-450, the ratio of product to hydrogen peroxide formation was virtually unchanged by the addition of acetone.

Acetone↗

Sex-related difference in the hepatic glutathione level and related enzyme activities in rat.

Age and sex differences in the hepatic glutathione level and related enzyme activities in rats of both sexes were investigated. At 7 weeks of age there was no significant difference in GSH levels between males and females, although a higher level of intracellular GSH was observed in male rats at 12 weeks of age. Hepatic gamma-glutamyl transpeptidase activities were significantly higher in females than in males at only 7 weeks of age. Glutathione peroxidase showed higher activities in females than in males. Conversely, glutathione S-transferase, glutathione reductase and glutathione synthesis rates were markedly higher in males than in females.

Aging↗

Effect of N-formyl-L-methionyl-L-leucyl-L-phenylalanine and its analogues on blood pressure.

Effects of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), the synthetic chemotactic peptide, and its analogues on blood pressure were investigated in the rabbit, rat, mouse, dog, cat and guinea pig. The administration of FMLP (5 micrograms/kg i.v.) induced the depressor effect in the rabbit but no effect was observed in the other animal species. The only peptide which showed a similar effect as FMLP was N-formyl-L-methionyl-L-methionyl-L-phenylalanine (FMMP) among the peptides relating to FMLP. Tachyphylaxis was observed in the hypotensive action induced by the two peptides.

Acetylcholine↗

Species difference in glutathione level and glutathione related enzyme activities in rats, mice, guinea pigs and hamsters.

Total glutathione (GSH and GSSG) level, and the activities of gamma-glutamylcysteine synthetase, gamma-glutamyltranspeptidase (gamma-GTP), glutathione S-transferase (GST), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) in the liver were investigated in rats, mice, guinea pigs and hamsters. Hepatic GSH level in rats, mice, guinea pigs and hamsters were 7.1, 7.8, 3.5 and 5.4 mM, respectively. The lower level of GSH in guinea pigs seems to be in part attributed to the higher activity of hepatic gamma-GTP, an enzyme which catalyzes GSH breakdown. Moreover, a marked species difference in the activities of GST, GSH-Px and GR was also observed. A 48 h-fasting resulted in a decrease of GSH and GSSG levels in rats, mice and guinea pigs, but not in hamsters. In addition, both nicotineamide adenine dinucleotide phosphate- and ascorbate-dependent lipid peroxidation produced by 9000 X g supernatant fraction in fasted animal species occurred most highly in the rat followed by hamster and guinea pig, and almost undetectable in mice. Thus, it suggests that the occurrence of lipid peroxidation in fasted animals may not be related to the hepatic GSH level, and rather, a lack of occurrence of lipid peroxidation in fasted mice may be due to the increased activity of GSH-Px activity.

Animals↗