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Biomedical subjects

K Imazu

Publications and source records attributed to K Imazu.

9 recordsLinked to original sources

Identification and quantitative analysis of urinary metabolites of dichloropropanols in rats.

Urinary metabolites of dichloropropanols in rats were analyzed by gas chromatography-mass spectrometry (GC/MS). Solutions of dichloropropanols consisting of 1, 3-dichloro-2-propanol (DC2P) and 2, 3-dichloro-1-propanol (DC1P) were diluted in a saline at the concentration of 100 mg/ml, and 0.1 ml of the solutions were subcutaneously injected into male Wistar rats weighing about 160g. The urine samples were collected over a period of 24 hours after the injections. DC2P and DC1P in the urine were extracted with ethylacetate and analyzed by a GC/MS. The derivatization procedure with 4-bromophenylboric acid after acetonitril extraction was applied for the analyses of diols in the urine. By the GC/MS analysis, 3-chloro-1, 2-propanediol (3CPD), 2-chloro-1, 3-propanediol (2CPD) and 1, 2-propanediol (PPD) were identified as the hydroxylated metabolites of dichlorpropanols. Based on the analytical results, the metabolic pathways of dichlorpropanols forming 3CPD and 2CPD, and then hydroxylating to PPD were elucidated.

Animals

[Effects of ethylene oxide inhalation on mice].

Male ddY mice were exposed to ethylene oxide (EO) at a concentration of 400 ppm, 6 hours a day, 3 days a week for 13 weeks and the effects of EO on the hepatic drug metabolizing enzymes were investigated. The liver and spleen weight per body weight did not change. Compared to the control group, the kidney weight of the exposed group increased while the testis weight decreased significantly. Hematological examination showed macrocytic anemia in the exposed group. Contents of microsomal cytochrome P-450 in the exposed group increased twice as much as that in the control group, while microsomal protein, cytochrome b5, protoheme and NADPH-cytochrome C reductase activity did not change. NADH-ferricyanide reductase activity of the exposed group increased significantly. Among the glutathione related enzymes in the liver, glutathione reductase and glutathione peroxidase activities in the exposed group decreased but glutathione-S-transferase activity increased significantly.

Administration, Inhalation

[Toxicity of dichloropropanols--changes in hematological findings and serum chemistry].

We investigated the toxicity of dichloropropanols (DCPs) in hematological findings and serum chemistry. The solutions of two isomers of DCPs, 1,3-dichloro-2-propanol (DC2P) and 2,3-dichloro-1-propanol (DC1P) were dissolved in saline at the concentration of 100 mg/ml, and 0.1 ml of each solution was subcutaneously injected into male Wistar rats weighing about 200 g. At 6 hours after the injections, in the DC2P group, the number of white blood cells and platelets showed a significant decrease. Transaminases, alkaline phosphatase and lactate dehydrogenase were greatly elevated. Blood urea nitrogen and creatinine also showed a significant increase. There were no changes in the measurements in the DC1P group. These results indicate that there is a prominent hepatotoxicity in DC2P, and that there is a considerable difference in the toxicity present in DC2P and DC1P. Furthermore, in the workplace where DCPs, especially DC2P, is used, the monitoring of the working environment and biological monitoring should be mandatory.

Alkaline Phosphatase

Effects of dimethylformamide on hepatic microsomal monooxygenase system and glutathione metabolism in rats.

The effects of repeated exposure to N,N-dimethylformamide (DMF) on hepatic microsomal monooxygenase system and glutathione metabolism were investigated. DMF was administered to Wistar male rats by subcutaneous (s.c.) injection at 0.5 ml/kg body weight daily for 1 week. Macroscopically, mild liver swelling was observed and liver weights significantly increased after 1 week of exposure to DMF. Hematological changes were not detected. In exposed rats, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, cholinesterase and total cholesterol significantly increased. Hepatic microsomal cytochrome P-450 and protoheme decreased by 34% and 24%, respectively, while microsomal protein and cytochrome b5 were not affected. NADH-ferricyanide reductase activity decreased by 24% while NADPH-cytochrome c reductase activity showed no change. Glutathione reductase (GR) activity showed a significant decrease after the first injection and remained depressed throughout the study, with no change in glutathione peroxidase (GPx) activity. Glutathione S-transferase (GST) activity showed a significant increase at 3 days after DMF treatment and gradually increased by 66% at 1 week. In a subsequent experiment with a single administration of DMF (4 ml/kg), reduced glutathione (GSH) in the liver was decreased by 28% at 8 h, but recovered to control levels by 24 h. These results indicate that DMF alters the hepatic microsomal monooxygenase system and glutathione metabolism. These findings may greatly contribute to the elucidation of the pathogenesis of DMF hepatotoxicity.

Animals

[Effects of ethylene glycol on drug metabolizing enzymes in rat liver].

We investigated the effects of ethylene glycol (EG) on the hepatic drug metabolizing enzymes. The exposed group was given 1% EG solution and the control group was provided with distilled water for 2 weeks ad libitum. The body weight of the exposed group was the same as that of the control group. The liver and kidney weight per body weight did not change. The daily drinking volume for the exposed group on the average showed an increase of 13.5% over that of the control group. Hematologically and biochemically, anemia, liver and renal dysfunction were not seen. The content of the hepatic microsomal cytochrome P-450 in the exposed group showed an increase of 17% over that of the control group, but the contents of cytochrome b5, protoheme and the activities of NADPH-cytochrome c reductase, NADH-ferricyanide reductase did not change. The activities of the hepatic cytosolic alcohol dehydrogenase and glutathione reductase, glutathione peroxidase, glutathione-S-transferase also did not change. These results indicate that the hepatic microsomal cytochrome P-450 takes part in the metabolism of EG.

Animals

[Effects of ethylene glycol on hepatic microsomal cytochrome P-450].

The effect of ethylene glycol on rat hepatic microsomal cytochrome P-450 was studied in vitro and in vivo. The destruction of cytochrome P-450 was not seen in vitro. The addition of 1 mM NADPH also did not change. When ethylene glycol was added to drinking water at a concentration of 1.0% for 7 days, there was no change in the contents of microsomal protein, cytochrome P-450, b5 and heme. While NADPH-cytochrome C reductase activity of the exposed group did not change, NADH-ferricyanide reductase activity increased significantly.

Animals

[Effects of sexual difference on the toxicity of ethylene oxide. III. The rat hepatic monooxygenase system].

Wistar male and female rats were exposed to ethylene oxide (EO) at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17 weeks and the effect of EO on the hepatic monooxygenase system in regards to the sex difference was investigated. Serum GOT of the exposed male rat slightly increased, but that of the female did not change. Contents of microsomal protein and cytochrome P-450 of the male exposed group decreased significantly compared to the male control group, but that of the female exposed group did not change. The change of cytochrome b5, protoheme and NADH-ferricyanide reductase activity of the female exposed group was the same as that of the male. Although NADPH-cytochrome c reductase activity of the male exposed group did not change, that of the female group exposed increased significantly when compared to the female control group. From these observations, we concluded that the effect of EO on the hepatic monooxygenase system was different between male and female.

Animals

[Delayed Sumithion intoxication].

A case of delayed Sumithion (fenitrothion) intoxication is reported. A 52-year-old man ingested 10 ml of Sumithion in order to commit suicide with alcohol and triazoram. Several hours later, he was admitted to our hospital because of clouding consciousness. On admission, he was somnolent, but had no other symptoms, especially suggested organophosphorus intoxication. After 40 hours, fasciculation and salivation, which are early symptoms of organophosphorus intoxication, gradually appeared. The concentration of Sumithion in the blood was measured during the course and its metabolism was represented phalmacokineticaly by a 2-compartment model. The retarded metabolism of the Sumithion was suggested by this model. It is considered that the retarded metabolism of Sumithion caused the delayed intoxication.

Biotransformation