• Title/Summary/Keyword: microsomes

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STEREOSELECTIVE METABOLISM AND INHIBITION OF LANSOPRAZOLE ENANTIOMERS ON HUMAN LIVER CYPs.

  • Kim, Kyung-Ah;Yoon, Young-Ran;Shin, Jae-Gook
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.196-196
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    • 2001
  • Stereoselective metabolism and inhibitory potential of lansoprazole enantiomers were evaluated from the incubational studies of human liver microsomes and eDNA-expressed CYP isoforms in vitro. The formation of lansoprazole sulfone from both enantiomers appeared to be catalyzed by single and low affinity enzyme. Lansoprazole 5-hydroxylation, however, appeared to be mediated by two kinetically distinct CYP enzymes.(omitted)

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In vitro Ccovalent Binding of SC-42867, PGE2 Antagonist, to Rat Liver Microsomal Proteins

  • Lee, Kyung-Tae
    • Archives of Pharmacal Research
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    • v.18 no.6
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    • pp.381-384
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    • 1995
  • Covalent binding of the reactive metabolites of SC_42867 to microsomal proteins has been examined. In the absence of inhibitor of cytochrome oxydase (.alpha.-naphtyl-isothiocyanate) or a radical scavenger (3-terthiobuty-4-hydroxyanisol), up to 4.0% of total redioactivity used in the assay could irreversibly bind to proteins. In the presence of an inhibitor, the highest percentage of covalent binding observed is 0.7% a significant decrease of the metabolism of SC42876 was observed. These results suggest in a cytochrome P-450 dependent generation of SC_42867 metabolites significantly take part in the covalent binding process.

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Antioxidants Isolated from Kalopanax pictus (엄나무 유래 신규 항산화 활성물질)

  • 김영희
    • Korean Journal of Plant Resources
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    • v.11
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    • pp.89-109
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    • 1998
  • Screening of new antioxidants form oriental medicines resulted in the isolation of a new antioxidative compound and eight known compounds from the stem bark of Kalopanax pictus. On the basis of various spectrosopic studies, the structure of the new compound was determined to be 4-rhamnose-3,5-dimethoxybenzoic acid methly ester. Other known compounds were identified as ferulic acid, 4,5,6,-trihydroxyflavanone, 2', 4',4' -trihydroxychalcone, caffeic acid, coniferyl alcohol, syringin, 1,3-di-O-caffeoylquinic acid. These compounds showed lipid peroxidation inhibitory acitivity in rat liver microsomes and free radical scavenging acitivity.

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Inhibitory Effects of Monovalent Cations on the Microsomal $Ca^{2+}$-ATpase in Tracheal Epithelial Cells

  • Cho, Kwang-Hyun;Kim, Young-Kee
    • Proceedings of the Korean Biophysical Society Conference
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    • 1999.06a
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    • pp.48-48
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    • 1999
  • Two types of vanadate-sensitive $Ca^{2+}$-ATPases have been characterized in the microsomes of tracheal epithelial cells, a high affinity vanadate-sensitive (HA VS) and a low affinity vanadate-sensitive (LAVS) $Ca^{2+}$-ATPases. The LA VS $Ca^{2+}$-ATPase was sensitive to thapsigargin, implying that it is an ER/SR-type $Ca^{2+}$-ATPase.(omitted)d)

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Investigation of Anti-aging Effect and Determination of Chemical Structures of Pine Needle Extract (PNE) through the Animal Experiments I. Effects of PNE on Oxygen Radicals and Their Scavenger Enzymes in Liver of SD Rats (동물실험을 통한 솔잎(松葉) 유효성분의 항노화효과 구명 및 구조 해명 I. 간장의 활성산소 및 제거효소에 미치는 솔잎 추출물의 영향)

  • 최진호;김대익;박수현;김동우;이종수;김현숙
    • Journal of Life Science
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    • v.9 no.4
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    • pp.466-472
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    • 1999
  • These studies were designed to investigate the effects of pine (Pinus densiflora Sieb et Zucc.) needle extract (PNE) on oxygen radicals and their scavenger enzymes in liver membranes of Sprague-Dawley (SD) rats as a study on investigation of anti-aging effect and determination of chemical structures of PNE through the animal experiments. Male SD rats were fed basic diets (control group) and experimental diets (0.5% and 1.0%-PNE group) for 6 weeks. There were no significant differences in hydroxyl radical (·OH) formations of liver mitochondria and microsomes in 0.5%-PNE group, while ·OH formations were significantly decreased (10% and 18%, respectively) in liver mitochondria and microsomes of 1.0%-PNE group compared with control group. Microsomal hydrogen peroxides and cytosolic superoxide radicals were remarkably decreased (20% and 20∼25%, respectively) in 0.5% and 1.0%-PNE groups compared with control group. Mn-SOD activities in mitochondria were significantly increased about 10% in 1.0%-PNE group, while Mn-SOD activities in mocrosomes were remarkably increased (16∼20%) in 0.5% and 1.0%-PNE groups compared with control group. There were no significant differences in Cu, Zn-SOD activities of liver cytosol in 0.5% and 1.0%-PNE groups, while glutathione peroxidase (GSHPx) and catalase (CAT) activities were significantly decreased (28∼30% and 15∼30%, respectively) in liver cytosols of 0.5% and 1.0%-PNE groups compared with control group. These results suggest that these PNE may play a effective role in a attenuating a oxygen radical formations and increasing a scavenger enzyme activities.

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Effects of Sea Tangle (Laminaria japonica) and Fucoidan Components on Chronic Degenerative Diseases (만성퇴행성 질환에 미치는 다시마(Laminaria japonica)와 후코이단 성분의 영향)

  • 최진호;김대익;박수현;김동우;이종수;유종현;정유섭
    • Journal of Life Science
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    • v.9 no.4
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    • pp.430-438
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    • 1999
  • This study was designed to investigate the effects of sea tangle (Laminaria japonica) extract and fucoidan components on chronic degenerative diseases. Sprague-Dawley(SD) male rats (210$\pm$5g) were fed experimental diets: Dasi-Ex group: dasima extract powder of 4.0% added to control diet; Fuco-I, II and III groups: fucoidan powder of 1, 2 and 3% added to Dasi-Ex group for 45 days. Triglyceride (TG) levels in serum were significantly lower (10~15%) in Fuco-I, II and III groups compared with control group. Total cholesterol levels were significantly decreased (7~10% and 15~ 35%) in brain mitochondria and microsomes of Fuco-II and III group compared with control group. LDL-cholesterol levels were remarkably decreased (20~30%) in Dasi-Ex and Fuco-I, II, III groups, but HDL-cholesterol levels were significantly increased (10~12%) in Fuco-II and III groups only compared with control group. The ratios of HDL/total cholesterol resulted in a marked increase (3 5~55%) in Dasi-Ex and Fuco-I, II, III groups, but atherogenic indices were remakably decreased (40~50%) in Dasi-Ex and Fuco-I, II, III groups compared with control group. Membrane fluidities were remarkably increased (45~70% and 38~42%, respectively) in brain mitochondria and microsomes of Fuco-II and III groups compared with control group. Administrations of fucoidan added to dasima effectively decreased TG, total and LDL-cholesterol, and atherogenic index, while also effectively increased HDL-cholesterol, HDL/total cholesterol ratio, and membrane fluidity, suggesting chronic degenerative diseases were very effectively prevented by the administration of fucoidan component.

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Modification of Hepatic Microsomal Cytochrome P450 2E1 Enzyme by Garlic Powder in Rat Hepatocarcinogenesis

  • Park, Kyung-Ae;Choi, Hay-Mie
    • BMB Reports
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    • v.30 no.1
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    • pp.73-79
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    • 1997
  • This study was designed to investigate the effects of dietary garlic powder on cytochrome P450 enzymes and membrane stability in murine hepatocarcinogenesis initiated by diethylnitrosamine (DEN). Male Sprague-Dawley rats received a single intraperitoneal injection of DEN (200 mg/kg body wt) dissolved in saline. After 2 weeks on a basal diet, animals were fed diets containing 0. 0.5. 2.0. or 5.0% garlic powder for 6 weeks, and were subjected to two-thirds partial hepatectomy. The areas of placental glutathione S-transferase (GST-P) positive foci were inhibited in rats fed with garlic diets. GST-P is the most effective marker for DEN-initiated lesions. Hepatic microsomal lipid peroxidation was significantly decreased in rats fed with 2.0 and 5.0% garlic powder diets compared with that observed in the control animals and hepatic microsomal glucose 6-phosphatase (G6Pase) activity was found to increase significantly in rats fed 0.5 and 2.0% garlic powder diets. Thus as little as 0.5% garlic powder has a positive effect on the stability of hepatic microsomal membranes. p-Nitrophenol hydroxylase (PNPH) activity and the level of cytochrome P450 2E1 protein in the hepatic microsomes from rats fed diets containing 2.0 and 5.0% garlic powder were much lower than those of control microsomes. Rats fed 5.0% garlic powder diets exhibited the lowest P450 2E1 activity and protein levels among groups. Pentoxyresorufin O-dealkylase activity and immunoblot (cytochrome P450 2B1) analyses were not different between groups. However, the levels of cytochrome P450 1A1/2 protein in rats fed 0.5 and 2.0% garlic powder were significantly induced compared to controls. These results suggest that 2.0% garlic powder is effective in inhibiting the areas of GST-P positive foci, modulating certain isoforms of cytochrome P450 enzymes and stabilizing the hepatic microsomal membrane. Thus, the selective modification of cytochrome P450 enzymes and membrane stability by dietary garlic powder may influence areas of GST-P positive foci and chemoprevention of post-initiation of rat hepatocarcinogenesis.

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Effect of Substrate Size on Activities of Thiocarbamides with the Human Flavin-containing Monooxygenase 3 (사람 Flavin-containing Monooxygenase 3의 Thiocarbamide 화합물의 기질 크기에 따른 효소활성에 관한 연구)

  • 김영미
    • Environmental Analysis Health and Toxicology
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    • v.16 no.2
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    • pp.97-102
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    • 2001
  • The flavin-containing monooxygenases(FMOs) (EC1.14.13.8) are NADPH0dependent flavoenzymes that catalyze oxidation of soft nucleophilic heteroatom centers in a range of structurally diverse compounds, including foods, drugs, pesticides, and other xenobiotics. In humans, FMO3 is quantitatively a major human liver monooxygenase. In the present study, the baculovirus expression vector system was used to overexpress human FMO3 in sect cells for stalytic studies. Microsomes isolated from Spodoptera frugiperda(Sf)9 cells infected with human FMO3 recombinant baculovirus catalyzed the NADPH-and O$_2$-dependent oxidation of methimazole, thiourea, and phenylthiourea. However there was no detectable activity with 1, 3-diphenylthiourea or larger thiocarbamides. Microsomes from control Sf9 cells were devoid of methimazole or thiourea S-oxygenase activity. 1, 3-diphenylthiourea is apparently completely excluded from the catalytic site, these amines drugs are probably approaching the upper size limits of xenobiotics accepted by human FMO3. The substrate specificity of this iosform in humans appears considerably more restriceted than that of pig, guinea pig, rat or rabbit FMO3.

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