• 제목/요약/키워드: microsomal enzymes

검색결과 107건 처리시간 0.034초

연령증가에 따른 마이크로솜 막지질 과산화수준의 변화와 해독효소계의 관계 (Correlation between microsomal lipid peroxidation levels and drug metabolizing enzymes in rats on various ages)

  • 조종후;황대우;박상열
    • 대한수의학회지
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    • 제43권4호
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    • pp.579-585
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    • 2003
  • The studies were carried out on the correlation between microsomal lipid peroxidation level and drug metabolizing enzyme activities in rat liver microsomal suspensions on various ages (2-week-old, 2, 4, 8, and 12-month-old). The lipid peroxidation levels of liver homogenates tended to be elevated in a 4-month-old rat livers, but it was a little decreased in 8 and 12-month-old rat livers. The lipid peroxidation levels of microsomal suspension was not shown any significant differences by ages. Lipid peroxidation levels and microsomal cytochrome P450 and NADPH-cytochrome c reductase activity showed a direct correlation (r=0.72 and r=0.64), respectively. The activities of cytochrome P450-dependent aminopyrine-N-demethylase and benzpyrene hydroxylase in rat liver microsomes were increased by ages up to 8-month-old rats and maintained in 12-month-old rats. The correlation between lipid peroxidation levels and these cytochrome-dependent enzyme activities showed a high direct correlation (r=0.97 and r=0.81), respectively.

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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    • 제30권1호
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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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Catechol-O-Methyltransferase Activity from Regenerating Liver after Partial Hepatectomy in Rats

  • ;;곽춘식
    • 대한의생명과학회지
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    • 제11권1호
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    • pp.45-49
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    • 2005
  • The change of catechol-O-methyltransferase (COMT) activity during regeneration of rat liver was studied. Cytosolic, mitochondrial and microsomal COMTs activities were estimated in regenerating rat livers over a period of ten days after $70\%$ (median and left lateral lobes) partial hepatectomy. The values of Km and Vmax in the hepatic enzymes were also measured. The activities of cytosolic and microsomal COMTs in regenerating rat liver after partial hepatectomy were found to be significantly increased between the second and the third day. Whereas the mitochondrial COMT activity did not change. The Vmax values of the cytosolic and microsomal COMTs in the regenerating rat liver were significantly increased at the second day after partial hepatectomy, however, the Km values of the above hepatic enzymes did not vary in all the experimental groups. Therefore, the results suggest that the biosynthesis of COMT was increased during the regeneration of rat liver.

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Ascorbic acid가 에탄올 대사효소에 미치는 영향 (Effect of Ascorbic Acid on the Activities of Ethanol Metabolizing Enzymes)

  • 김용식
    • 대한약리학회지
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    • 제20권1호
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    • pp.47-54
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    • 1984
  • Effect of ascorbic acid on various hepatic ethanol metabolizing enzymes including alcohol dehydrogenase(ADH), the microsomal . ethanol oxidizing system(MEOS), and catalase was quantitatively evaluated in liver microsomal and cytosolic preparation from Sprague-Dowley rats. In present study, ADH activities were no changed significantly by ascorbic acid. The MEOS activity, dependent on NADPH and $O_2$, was affected by azide (inhibitor of catalase) or exogenous catalase. In the presence of ascorbic acid, ethanol oxidation by rat liver microsomal preparation reacted with NADPH-generating system was increased by up to 22.5%, but decreased when liver microsome was reacted with $H_2O_2$ generated by xanthine and xanthine oxidase. Increase in the activity of the MEOS in the presence of ascorbic acid was greater in liver microsomal preparation pretreated with azide. Also ascorbic acid oxidized ethanol nonenzymatically. This ethanol oxidation induced by ascorbic acid was inhibited by OH radical scavengers (thiourea, sodium benzoate), but was not much affected by superoxide dismutase. From these results it was suggested that ascorbic acidcould interact directly with the MEOS, then promote the oxidation of ethanol. And, to some extent, ${\cdot}OH$-radicals or other radicals generated during the spontaneous autooxidation of ascorbic acid may be responsible for the production of acetaldehyde from ethanol.

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Inhibition of hepatic microsomal drug-metabolizing enzymes by imperatorin

  • Shin, Kuk-Hyun;Woo, Won-Sick
    • Archives of Pharmacal Research
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    • 제9권2호
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    • pp.81-86
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    • 1986
  • The effect of imperatorin on hepatic microsomal mixed function oxidases (MF0) was investigated. On acute treatment, imperatorin (30 mg/kg, i.p) caused a significant reduction in activities of hepatic aminopyrine N-demethylase, hexobarbital hydroxylase and aniline hydroxylase as well as cytochrome p0450 content in rats and mice. Kinetic studies on rat liver enzymes revealed that imperatorin appeared to be a competitive inhibitor of aminopyrine N-demethylase (Ki,0.007 mM), whereas a non-competitive inhibitor of hexobarbital hydroxylase (Ki, 0.0148 mM). Imperatorin also inhibited non-competitively aniline metabolism (Ki 0.2 mM). Imperatorin binds to phenobarbital-induced cytochrome p-450 to give a typical type 1 binding sepctrum (max. 388nm, min 422 nm). Multiple administrations of imperatorin (30 mg/kg. i. p. daily for 7 days) to mice shortended markedly the duration of hexobarbital narcosis and increased activities of hepatic aminopyrine N-demethylase and hexobarbital hydroxylase and the level of cytochrome p-450 where as aniline hydroxylase activity was unaffected.

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Catechol-O-Methyltransferase Activity in Cholestatic Rat's Liver Induced by Bile Duct Ligation

  • Mun, Kyo-Cheol
    • BMB Reports
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    • 제29권2호
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    • pp.142-145
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    • 1996
  • To investigate the cause of increased plasma catecholamine levels in liver disease, catechol-O-methyltransferase (COMT), which provides a major route of catabolism for circulating catecholamines, was studied under the cholestasis induced by mechanical biliary obstruction in rats. Monoamine oxidase (MAO) activity and the $K_m$ and $V_{max}$ values for both enzymes were also measured. Cytosolic, microsomal, and mitochondrial COMT activities in the cholestatic liver were significantly decreased throughout the experiment. Microsomal, and mitochondrial MAO activity in the cholestatic liver were also significantly decreased. Vmax values of COMT and MAO were lower. Serum COMT and MAO activities were detected after CBD ligation. These results indicate that plasma catecholamine levels are increased in liver disease due to decreased hepatic degradation of catecholamines by decreased activities of COMT and MAO. The decreased activity of these enzymes is caused by decreased biosynthesis and by flowage into the blood from the damaged hepatocyte.

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Effects of Extrahepatic Cholestasis on Hepatic $\alpha$-D-Mannosidase Activity in Chronic Ethanol Intoxicated Rats

  • Si-Woo Bae;Chun-Sik Kwak;Chong-Guk Yoon
    • 대한의생명과학회지
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    • 제9권1호
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    • pp.21-27
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    • 2003
  • Hepatic subcellular $\alpha$-D-mannosidases activities and its Km and Vmax values were determined in chronic ethanol intoxicated rats with extrahepatic cholestasis induced by common bile duct ligation to manifest the biochemical background of alcohol drinking hazard under the hepatobiliary disease. In case of extrahepatic cholestasis, chronic ethanol intoxication in animals led to the increased activities of liver Golgi and microsomal $\alpha$-D-mannosidase as well as the Vmax values of these enzymes. However, the difference of Km values on hepatic subcellular enzymes were not found between the experimental groups. Therefore, the results indicate that the liver Golgi and microsomal $\alpha$-D-mannosidase may be more induced in chronic ethanol intoxication animals in case of cholestasis. Accordingly, the resulting data supported the fact that alcoholic drinks may led to enhancement of the hepatobiliary liver damage.

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Indole, Indole-3-calbinol 및 Benzofuran이 간장 microsome과 cytosol의 약물대사 효소 활성도에 미치는 영향 (Differential Effects of Indole, Indole-3-carbinol and Benzofuran on Several Microsomal and Cytosolic Enzyme Activities in Mouse Liver)

  • 차영남;;;정진호
    • 대한약리학회지
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    • 제21권1호
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    • pp.1-11
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    • 1985
  • 이물질(xenobiotics) 대사에 관여하는 간장 microsome과 cytosol 효소 활성에 indole, indole-3-carbinol 및 benzofuran이 미치는 영향을 검색하기위하여 마우스에 이들 약물을 각각 5 mmole/kg씩 10일간 투여하여 다음 몇 가지의 성적을 얻었다. Benzofuran은 microsome 효소인 aniline hydroxylase, 7-ethoxycoumarin O-deethylase, p-nitrophenol UDPGA-transferase, epoxide hydrolase와 cytosol 효소인 glutathione S-tranferase, NADH : quinone reductase, UDP-glucose dehydrogenase의 활성도를 증가시켰다. 그러나 benzofuran과는 구조적으로 furan ring내의 N원소가 O원소로 치환되었을 뿐 주된 구조가 유사한 indole과 indole-3-carbinol 투여로는 UDPGA-transferase와 NADH: quinone reductase의 활성도 증가를 볼 수 없었으며, 특히 indole은 NADPH : cytochrome C reductase만을 증가시킨데 비하여 구조상 indole에 carbinol (methanol)기가 붙은 indole-3-carbinol은 수종의 mixed function oxidase와 아울러 특히 epoxide hydrolase의 활성도 역시 증가시켰다. 이러한 결과는 benzofuran과 indole-3-carbinol에 의한 epoxide hydrolase 활성도 증가의 기전의 일부를 설명할 수 있을 것으로 생각된다.

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식이지질의 조절이 흰쥐 적출관류간장에 의한 Ethoxycoumarin 대사기능에 미치는 영향 (Effects of Dietary Lipid on Ethoxycoumarin Metabolism in Isolated Perfused Rat Liver)

  • 이기완
    • Journal of Nutrition and Health
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    • 제24권6호
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    • pp.485-495
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    • 1991
  • Using isolated perfused livers obtained from rats that have been fed saturated and unsatu-rated fatty acid diets the rates of hepatic microsomal oxidation of 7-ethoxycoumarin(EC) to 7-hydroxycoumarin(HC) and the rates of subsequent conjugation of the produced HC to its glucuronide and sulfate esters have been determined. Prior to preparing the isolated perfused livers. rats were fed either fat free diet 10% beef tallow diet or 10% corn oil diet for 3 weeks. The rates of oxidation from EC to HC and also of the subsequent glucuronidation of HC were higher in the corn oil diet group than those found for the fat free and beef tallow diet groups. When the concentrations of infusing EC were increased stepwise there was a dose-dependnet increase for the release of the glucuronide form of HC metabolites at the expense of the sulfate ester form. This dose dependant shift observed for the corn oil group was more significnat than those found for other groups. These results indicate that corn oil feeding has produced enhancement in the rates of hepatic microsomal drug oxidation and glucuronide conjugation the reactions catalyzed by enzymes embedded in the hepatic microsomal membranes.

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Reversible Inhibitory Effect of $Hg^{2+}$ on the Microsomal $H^+$-ATPases

  • Shin, Dae-Seop;Cho, Kwang-Hyun;Kim, Young-Kee
    • 한국생물물리학회:학술대회논문집
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    • 한국생물물리학회 1999년도 학술발표회 진행표 및 논문초록
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    • pp.49-49
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    • 1999
  • $H^{+}$-ATPases play major roles in various cellular physiology. In order to characterize the effects of heavy metal ions on the activity of $H^{+}$-ATPases, microsomes were isolated from the roots of tomato grown hydroponically. The activity of microsomal $H^{+}$-ATPase was measured by an enzyme-coupled assay. H $g^{2+}$ inhibited the activity of microsomal $H^{+}$-ATPase as a dose-dependent manner, F $e^{3+}$ and Z $n^{2+}$ inhibited the activity although they also blocked the activities of enzymes used in the assay, and C $s^{+}$ and $Ba^{2+}$ showed no significant effect.(omitted)d)ted)d)

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