• Title/Summary/Keyword: cytochrome P450 enzyme system

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Effects of γ-Irradiated Pork Diet on Cytochrome P-450 System, Microsome Glucose 6-Phosphatase Activity and Antioxidative Defense Systems in Rat Hepatocarcinogenesis

  • Kang, Il-Jun;Kim, Jung-Hee;Chung, Cha-Kwon
    • Preventive Nutrition and Food Science
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    • v.8 no.2
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    • pp.158-161
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    • 2003
  • This study investigated the effects of a ${\gamma}$-irradiated pork (0-30 kGy) diet on lipid peroxidation, cytochrome P-450 content, microsomal glucose 6-phosphatase (G-6-Pase) activity and antioxidative defense systems in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. The body weight of rats fed irradiated diets did not change significantly. Liver weight was significantly increased by the administration of DEN, but not by irradiated diets at any dose level. There were no significant effects of gamma irradiation on the content of microsomal malondialdehyde (MDA), cytochrome P-450, or on the activity of G-6-Pase. However, with DEN treatment, cytochrome P-450 content was significantly increased while microsomal G-6-Pase activity was significantly decreased. The ${\gamma}$-irradiated diet supplement did not affect serum retinol or $\alpha$-tocopherol concentrations. However, it did cause a significant decrease in hepatic retinol at 30 kGy. With DEN treatment, hepatic retinol content was even more significantly (p<0.05) decreased compared to the non-irradiated control. The enzyme activities related to antioxidative defense systems, including glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rx) and glutathione S-transferase (GST) were not affected by gamma irradiation. Those results suggest that an irradiated pork diet up to 30 kGy may not cause a health hazard in experimental animals.

Comparative effects of nicotine and diazinon on larval mortality and activity of cytochrome P-450 monooxygenases in Helicoverpa assulta and Spodoptera exigua (담배나방과 파밤나방의 유충사망률과 cytochrome P-450 monooxygenases의 활성에 미치는 니코틴과 다이아지논의 영향)

  • 이정호;부경생
    • Korean journal of applied entomology
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    • v.32 no.2
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    • pp.225-235
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    • 1993
  • This study was carried out to investigate effects of diazinon, an organophosphate, and nicotine, a plant~originated toxic chemical, on larval mortality and activity of cytochrome P-45D monooxygenases, a major detoxifwation enzyme system, in Helicoverpa assulta and Spodoptera exigua. Diazinon treatment gave a higher mortaliLy to H. assulta larvae than S. exigua larvae. In contrast to the case of diazinon, nicotine caused a higher mortahty to S. exigua than to H. assulla larvae. It was partly due to the fact that nicotine induced the actiVIty of midgut cytochrome P-450 monooxygenases (MFO) more than diazinon did in If assulta larvae. When If. aSSlllta larvae were reared on their host p\am. NicotwlIa tuoocum leaves, other componentS were mostly metabolized with the exception of dietary nicotine.

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Heterogeneous Natures of the Microbial Steroid $9{\alpha}$-Hydroxylase in Nocardioforms

  • Kang, Hee-Kyoung;Lee, Sang-Sup
    • Archives of Pharmacal Research
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    • v.20 no.6
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    • pp.519-524
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    • 1997
  • Steroid $9{\alpha}$-hydroxylase is an enzyme found in nocardioform microorganisms which can utilize steroids as a sole carbon source. After fractional centrifugation of the cell homogenates, the enzyme activity in Nocardia and Rhodococcus was found in cytoplasmic membrane fraction. On the contrary, Mycobacterium had its 9.alpha.-hydroxylation activity in cytosolic fraction. To characterize the enzyme in these microorganisms, several potential inhibitors of 9.alpha.-hydroxylase were tested and the cofactor requirement for the same enzyme was also examined. The inhibitory effect of ferrous ion chelators indicated involvement of iron containing proteins in the 9.alpha.-hydroxylase system. On the other hand, metyrapone, an inhibitor known to be specific for cytochrome P450 interfered with the enzyme in Mycobacterium, but didn't inhibit the enzyme activity in Nocardia and Rhodococcus. While the $9{\alpha}$-hydroxylase system in Nocardia and Rhodococcus required NADPH, NADH was required as an election donor in Mycobacterium.

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Toxic action of N-dimethylphosphinothioyl carbofuran by oxidative activation process (산화적 활성화 과정을 통한 N-dimethoxyphosphinothioyl carbofuran의 독성발현)

  • Yang, Kyew-Wan;Lee, Seog-Jong;Kim, Song-Mun;Han, Dae-Sung;Hur, Jang-Hyun
    • The Korean Journal of Pesticide Science
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    • v.2 no.2
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    • pp.10-15
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    • 1998
  • The bimolecular inhibition rate constants of carbofuran and N-dimethylphosphinothioyl carbofuran(PSC) to acetylcholinesterase(AChE) were $7.7{\times}10^{5}\;M^{-1}{\cdot}min^{-1}$ and $1.2{\times}10^{3}\;M^{-1}{\cdot}min^{-1}$, respectively. These results showed that PSC required a bioactivation process for its toxic action because it didn't inhibit the target enzyme effectively. The potency of PSC as an inhibitor of AChE increased when PSC and AChE were incubated with microsomes fortified with NADPH compared with microsome alone. Piperonyl butoxide(PBO) addition to these coupled systems greatly reduced the inhibition of the target enzyme by blocking the bioactivation process. In vivo inhibition study of mouse brain AChE, $I_{50}$ value for AChE was 28 mg/kg for PSC and the value increased to 57 mg/kg when PBO was pretreated. This result showed that cytochrome $P_{450}$ would also play a role in the bioactivation process of PSC in vivo. And conversioin of carbofuran from PSC was 55 % in a chemical oxidation system using meta-chloroperoxybenzoic acid. The oxidative activation of PSC to carbofuran was shown to be essential for showing its toxicological action and cytochrome $P_{450}$ was identified as an important enzyme which participated in this process.

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Inhibitory Effect of a Drug Metabolizing Enzyme CYP3A4 on Spices (향신료의 약물대사효소 CYP3A4 저해효과)

  • Cha, Bae-Cheon
    • Korean Journal of Pharmacognosy
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    • v.34 no.1 s.132
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    • pp.86-90
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    • 2003
  • For the determination of inhibiting cytochrome P450(CYP)3A4 activity, an improvement HPLC method was established by using a new internal standard and solvent system. Moreover, CYP3A4 amount for a optimum reaction of enzyme was determined by a comparative study with a variety concentration of enzyme. Using a established method, inhibitory effect of CYP3A4 that is drug metabolizing enzyme Investigated on EtOAc extracts of 5-class spices. As a result of experiment, EtOAc extract of white pepper (Piper nigrum L.) showed strong inhibitory activity. On a continuous experiment, the fraction 2, 4 and 5 of while pepper extract showed remarkable inhibitory activity. Pipeline, a main constituent of pepper was not included in these fraction. It is suggested that major compounds for the inhibitory activity of white pepper may be other ingredient that is not piperine.

Production of Monoclonal Antibody to Polychlorinated Biphenyl Induced Cytochrome P-450 LMII in Rat Liver (Polychlorinated Biphenyl에 의한 백서간 Cytochrome P-$450_{LMII}$에 대한 Monoclonal Antibody 생성에 관한 연구)

  • Kim, Jung-Hye;Kim, Jae-Ryong;Lee, Ki-Yung
    • Journal of Yeungnam Medical Science
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    • v.3 no.1
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    • pp.103-110
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    • 1986
  • Cytochrome P-450(CP-450) is one of the three components of the liver microsomal enzyme system which hydroxylates fatty acids, hydrocarbons and a variety of drugs and other foreign compounds. Female Balb/c mice were immunized with purified polychlorinated bipheny(PCB)-induced CP-450 LMII. The spleen cells derived from immunized mice were fused with $SP^2$ myeloma cells using polyethylene glycol(PEG 3500). The hybrid cells were selected by hypoxanthine-aminopterine and thymidine(HAT) medium and the culture fluid were screened by enzyme-linked immunosorbent assay to CP450 LMII. The hybrid cess(${\times}10^7$) were innoculated into intraperitoneal cavity of Balb/c mice for the purpose of production of ascitic fluids. Monoclonal antibody(Mab) was purified from ascitic fluid by DEAE cellulose ion exchange chromatography and $I^{125}$-labeled Mab was also confirmed by autoradiography and SDS-polyacrylamide gel electrophoresis (MW : 55,000 and 110,000).

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Effect of Vitamin A and $B_2$ Derivatives on Aminopyrine Demethylase Activity (비타민 A 및 $B_2$ 유도체의 Aminopyrine Demethylase 활성도에 대한 영향)

  • 이향우
    • YAKHAK HOEJI
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    • v.28 no.1
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    • pp.53-59
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    • 1984
  • Drug-metabolizing system which has the important role in drug metabolism is localized in smooth endoplasmic reticulum of hepatocytes and is composed of NADPH, NADPH-cytochrome $P_{450}$ reductase, cytochrome $P_{450}$ and others. It is well known that the enzyme system is induced by phenobarbital and methylcholanthrene. Lipid peroxidation is reaction of oxidative deterioration of polyunsaturated lipids. Formation of lipid peroxides in liver microsome has been found to produce degradation of phospholipid, which are major components of microsomal membrane. The relationship between the formation of lipid oxides and the activities of drug-metabolizing enzyme in the liver of rats was reported by several investigators. In this study the effect of riboflavin tetrabutylate, an antioxidant on lipid peroxidation, specially the relationship between lipid peroxidation and drug-metabolizing enzyme system was investigated. In addition the effect of vitamin A derivatives, such as retinoic acid and retinoid on the enzyme was also observed. Results are summarized as followings. 1) The pretretment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to $CCl_{4}$ treatment. 2) The increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. 3) The pretreatment with riboflavin tetrabutylate also prevented the decrease of drug-metabolizing enzyme caused by $CCl_{4}$. 4) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity.

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The Effect of Korean Red Ginseng Water-extract on Aging-related Changes in the Xenobiotic Metabolizing Enzyme System in the Liver of Rats (홍삼의 물추출물이 노화에 따른 흰쥐 간의 이물질대사 효소계에 미치는 영향)

  • Lee, Dong-Wook;Lim, Heung-Bin
    • Korean Journal of Medicinal Crop Science
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    • v.14 no.6
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    • pp.329-335
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    • 2006
  • The present study was designed to investigate aging-related effects on the activities of xenobiotic metabolizing enzymes of rat liver by dietary supplementation of Korean red ginseng water-extract. Rat did not show any discernible signs of the rejection symptoms, and blood GOT and GPT levels were not influenced by ginseng water extracts, Cytochrome 450 levels and NADPH cytochrome P45O reductase, p-450 dependent ethoxycoumarin O-deethylase, and benzphetamine N-demethylase activities were decreased with aging, however, these phase I system enzymes activities in the ginseng group of24 months were well maintained compared with normal group. But, Levels of cytochrome bs and NADH-cytochrome b$_5$ reductase activities were also decreased with aging and were not found a clear difference between two groups. Glutathione-s-transferase activity, phase II enzyme system, in liver cytosols was also decreased in old ages, but the degree of decrease was higher in normal group than in giuseng supplemented group. These results indicate that long-term supplementation of red ginseng water extracts from weaning to 24 months do not show any side effects to rats, and retard age-related deteriorations of xenobiotic metabolizing enzymes activities in old ages.

Study on the Hepatoprotective Effect and Cytochrome P450 Regulation of Scutellaria Radix (황금의 간세포 보호활성 및 cytochrome P450 발현 조절에 관한 연구)

  • Ha, Ki-Tae;Jeong, Sang-Sin;Kim, Cheorl-Ho;Choi, Dall-Yeong;Kim, June-Ki
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.1
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    • pp.155-161
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    • 2008
  • Carbon tetrachloride $(CCl_4)-induced$ liver injury depends on a toxic agent that has to be metabolized by the liver NAPDH-cytochrome P450 enzyme system to a highly reactive intermediate. Although several isoforms of cytochrome P450 may metabolize $CC1_4$, attention has been focused largely on the cytochrome P450 2E1 (CYP2E1), which is ethanol-inducible. Alternations in the activity of CYP2E1 affect the susceptibility to hepatic injury from $CC1_4$. In this study, the liver protective effect of the hot water extracts of Scutellaria radix (SR) was investigated. The SR exhibited a hepatoprotective activity against $CCl_4-induced$ liver damage in Chang liver cells. The expression of CYP2E1, measured by RT-PCR and Western blot analysis, was significantly decreased by SR treatment in Chang cells. Based on these findings, it is suggested that hepatoprotective effect of SR possibly related to downregulation of CYP2E1 expression.

Responses in Hepatic Xenobiotic Metabolizing Enzymes and Sex Hormones of Yellowfin Goby Acanthogobius flavimanus in Nakdong Estuary (낙동강 하구에서 채집한 문절망둑 Acanthogobius flavimanus의 간장 약물대사효소계와 성호르몬 농도)

  • Lee, Ji-Seon;Jeong, Jee-Hyun;Han, Chang-Hee;Shim, Won-Joon;Jeon, Joong-Kyun
    • Korean Journal of Environmental Biology
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    • v.26 no.2
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    • pp.87-93
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    • 2008
  • To assess effects of contaminants on fish in Nakdong river, feral yellowfin goby Acanthogobius flavimanus were caugt in two different sites and its hepatic monooxygenase enzyme, including cytochrome P450 (CYP), NADPH-cytochrome P450 reductase (P450R), NADH-cytochrome b5 reductase (b5R), ethoxyresorufin deethylase (EROD), glutathione S-transferase (GST) were quantitatively determined. Gonadosomatic index (GSI), hepatosomatic index (HSI) and three sex steroid hormone (17$\beta$-estradiol, E2; testosterone, T; 11-ketotestosterone, 11-KT) levels of the fish were also investigated. HSI of fish from polluted site (site 1) were significantly higher than that of unpolluted site (site 2), but GSI levels were significantly lower in polluted site. No significant differences in plasma 11-KT and T levels were observed in two sites surveyed. E2 level was, however, significantly (p<0.05) higher in female fish from site 1 than site 2. In addition, hepatic EROD activity and CYP level of site 1 fish were lower than those of site 2 fish, whereas relatively high levels of P450R, b5R and GST activities were found in site 1. The results imply that yellowfin goby, especially female fish in Nakdong river estuary are affected from contaminants disrupting sex steroid hormone system.