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K Endoh

Publications and source records attributed to K Endoh.

At least 91 records · Page 5Linked to original sources

[The relationship between external and internal doses of trichloroethylene. A simulation study using a physiological pharmacokinetic model].

The relationship between external dose and internal dose of trichloroethylene (Tri) was analyzed by using a physiological simulation model. The external dose of Tri was represented by the time-weighted average (TWA) concentration in inhaled air or by the product of exposure concentration and exposure duration, and the internal dose by the area under the curve (AUC) of Tri blood concentration or by the cumulative amount of total trichloro compounds (TTC) in urine. If TWA concentrations were equal, the internal doses were also equal irrespective of whether Tri exposure was continuous, intermittent, or random. Both AUC of Tri and cumulative amounts of urinary TTC increased linearly with increase of Tri concentration in inhaled air up to 100 ppm. The increase at exposure concentrations between 100 and 500 ppm was non-linear. At concentrations above 500 ppm where Tri metabolism was saturated, AUC increased linearly again but much more sharply than the increase at concentrations below 100 ppm. In contrast, the increase of cumulative amounts approached a plateau along with Tri exposure concentration. If the exposure concentration was below the level when saturation of Tri metabolism did not occur, equal products of Tri concentration and exposure duration resulted in almost the same internal dose. In general, however, the AUC of blood concentration in a high-concentration, short-duration exposure was larger than that of a low-concentration, long-duration exposure, whereas the cumulative amount of TTC was larger in the latter than in the former.

Administration, Inhalation↗

[Individual differences in the kinetic behavior of trichloroethylene. A simulation study using a physiological pharmacokinetic model].

Toxicokinetic behaviors of trichloroetylene were analyzed by using a physiological simulation model and the effects of physical activity (work load), body fat content and alcohol consumption on the uptake, distribution and excretion of this solvent were studied. This simulation study was not intended to predict the exact kinetic behavior of trichloroethylene in man, but to show how a physiological pharmacokinetic model is used to elucidate some aspects of individual differences in the kinetics of organic solvent vapors in human exposure. The following results were obtained: 1. Physical activity of 50 W during exposure greatly increases the blood concentration of trichloroethylene and the urinary excretion of its metabolites, whereas the activity after exposure exerts only a marginal influence. 2. Body fat content substantially affects the kinetic behavior of trichloroethylene only when the blood flow through fat tissue is assumed to increase according to the increase in body fat volume. In general, both blood concentration of trichloroethylene and urinary excretion rate of its metabolites are higher in slim men than in obese men during exposure, and the relationship is reversed between obese and slim men after exposure. 3. Ethanol-induced inhibition of trichloroethylene metabolism causes a marked change in the kinetic behavior when trichloroethylene exposure level is low, whereas the greater is the effect of ethanol-induced enhancement of metabolism, the higher the exposure level.

Adipose Tissue↗

Rec-assay of human bile for mutagenicity and co-mutagenicity.

Spore rec-assay of human bile was conducted by the Bacillus subtilis test system to examine possible mutagenicity and co-mutagenicity. Of 26 samples examined, 8 (30.8%) showed mutagenic activity and 23 (88.5%) enhanced the mutagenic activity of mitomycin C.

Bacillus subtilis↗

Role of PAF in ischemia-reperfusion injury in the rat stomach.

Ischemia-reperfusion induced extensive gastric mucosal injury and an increase in chemiluminescence activity of neutrophils obtained from the portal vein in hemorrhagic shock rats. CV-3988, a selective antagonist of platelet activating factor (PAF), significantly reduced the gross and histologic gastric damage, and the increase in chemiluminescence activity of neutrophils. These results suggest that PAF generated on hypoxia might stimulate oxygen radical production by neutrophils, resulting in the occurrence of gastric injury in hemorrhagic shock rats.

Animals↗

Mutagenicity of the ash of rice straws by Ames' test.

Mutagenicity of fly ashes and bottom ashes of rice straw and rice husk was assayed by Ames' test. With respect to rice-straw ash, the extract from the fly ash was found to be more mutagenic than that from the bottom ash. In the case of rice husk, the mutagenicity of extract from the bottom ash was stronger than that from the fly ash. The extract from rice-husk bottom ash showed the strongest mutagenic activity among the four.

Air Pollutants↗

Epoxidation of androsta-5,16-dien-3 beta-ol by hepatic microsomal lipid peroxidation.

Male rat liver microsomes oxidized androsta-5,16-dien-3 beta-ol (delta 16-ANDO) to delta 16-ANDO-5,6 alpha-, -5,6 beta-, -16,17 alpha-, and -16,17 beta-epoxides and delta 16-ANDO-5 alpha,6 beta-, -16 alpha,17 beta-, and -16 beta,17 alpha-glycols in the presence of an NADPH-generating system and the microsomal lipid peroxidation accelerator, Fe2+-ADP. The hepatic microsomes hydrolyzed all the delta 16-ANDO epoxides to the glycols. delta 16-ANDO-5 alpha,6 beta-glycol was the sole metabolite from both 5,6 alpha- and 5,6 beta-epoxides. Microsomal epoxide hydrolase also hydrolyzed delta 16-ANDO-16,17 alpha-epoxide specifically to the 16 beta,17 alpha-glycol and the isomeric 16,17 beta-epoxide to the 16 alpha,17 beta- and 16 beta,17 alpha-glycols approximately in the equal ratio. The delta 5-epoxidation of delta 16-ANDO by microsomes occurred only under the conditions that lipid peroxidation took place. Direct evidence was obtained for the participation of microsomal lipid hydroperoxides in the epoxidation of delta 16-ANDO by using photochemically prepared hydroperoxides of phospholipids separated from the hepatic microsomes. The hydroperoxides generated active oxygens, tentatively assigned as alk(ylper)oxy radicals, by the action of ferrous ion and epoxidized delta 16-ANDO to afford the 5,6- and 16,17-epoxides. The Fe2+-ADP-mediated epoxidation of delta 16-ANDO by the phospholipid hydroperoxides occurred preferentially at delta 5 to delta 16 and afforded the 5,6 beta-epoxide in a higher ratio than the 5,6 alpha-epoxide, similar to the Fe2+-ADP-mediated microsomal epoxidation, while the alpha-epoxide was preferentially formed to the beta-epoxide for delta 16 in the epoxidation by both systems.

Androstenols↗

[Inhibitory effect on the release of mediators from rat peritoneal exudate cells and the antagonistic effect against mediators of MY-5116 and other anti-allergic agents].

The effects of a new anti-allergic agent, MY-5116: isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c] quinoline-2-carboxylate, and its main metabolite, MY-1250: 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c] quinoline-2-carboxylic acid, on 48 hr homologous PCA (PCA) in rats and the release of histamine and SRS from rat peritoneal exudate cells (PEC) induced by IgE antibody in comparison with other anti-allergic agents were investigated. Also, the effects of MY-5116 and MY-1250 on antagonistic action against histamine and LTD4 were studied. MY-5116, tranilast and ketotifen inhibited PCA at oral doses of more than 3 mg/kg, 300 mg/kg and 0.3 mg/kg, respectively. MY-1250, DSCG and tranilast inhibited significantly the release of histamine from PEC induced by the antigen-antibody reaction in a dose-dependent manner, and the values of IC50 were 4.9 X 10(-8), 4.8 X 10(-6) and 4.6 X 10(-6) g/ml, respectively. Ketotifen inhibited significantly the release of histamine at a concentration of 10(-5) g/ml, but it accelerated significantly the release of histamine from PEC at a concentration of 10(-4) g/ml. MY-1250 and tranilast suppressed the release of SRS from PEC induced by the antigen-antibody reaction. The values of IC50 of MY-1250 and tranilast were 1.5 X 10(-6) and 2.1 X 10(-6) g/ml, respectively. MY-1250 suppressed slightly the release of SRS from PEC induced by A23187. MY-5116 showed no effect on the increase of vascular permeability induced by histamine, bradykinin and serotonin in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of MY-5116 on experimental animal models of type I-type IV allergic reactions and the formation of IgE antibody].

The effects of a new anti-allergic agent, MY-5116: isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c] quinoline-2-carboxylate, on experimental animal models of type I approximately type IV allergic reactions and the formation of IgE antibody were investigated. MY-5116 administered intraperitoneally at doses of 30 and 100 mg/kg suppressed significantly the homologous PCA in guinea pigs. MY-5116 administered intraperitoneally at the dose of 100 mg/kg also suppressed significantly the heterologous PCA in guinea pigs. MY-1250, the main active metabolite of MY-5116, showed no suppression on the Schultz-Dale reaction in guinea pigs, and MY-5116 showed no inhibition on the active systemic anaphylaxis in mice (type I). MY-5116 showed no inhibition on the reversed cutaneous anaphylaxis in rats (type II), the Forssman reaction in guinea pigs (type II), the Arthus reaction in mice (type III) and the delayed type hypersensitivity in mice (type IV). MY-5116 showed no suppression on the formation of IgE antibody in C3H/He and BALB/c mice and rats. From these results, it is concluded that MY-5116 selectively suppresses the experimental models of type I allergic reaction.

Anaphylaxis↗

A reactive hydroxymethyl sulfate ester formed regioselectively from the carcinogen, 7,12-dihydroxymethylbenz[alpha]anthracene, by rat liver sulfotransferase.

The carcinogen, 7,12-dihydroxymethylbenz[alpha]anthracene (DHBA), was regioselectively conjugated in the presence of 3'-phosphoadenosine 5'-phosphosulfate by male rat liver cytosolic sulfotransferase to DHBA 7-sulfate. The sulfate ester was highly reactive and showed a potent, intrinsic mutagenicity toward Salmonella typhimurium TA 98.

Animals↗