• Title/Summary/Keyword: cytochrome P450s

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ROLE OF METABOLISM BY FLAVIN-CONTAINING MONOOXYGENASE IN THIOACETAMIDE-INDUCED IMMUNOSUPPRESSION

  • Woo S. Koh;Lee, Jeong W.;Tae C. Jeong
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.73-73
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    • 2002
  • Thioacetamide has been known to cause immune suppression. The object of the present study is to investigate the role of metabolic activation by flavin- containing monooxygenases (FMO) in thioacetamide-induced immune response. To determine whether the metabolites of thioacetamide produced by FMO causes the immunosuppression, methimazole (MMI), an FMO inhibitor, was used to block the FMO pathway.(omitted)

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Effects of Korean traditional herbal formula for common cold on the activities of human CYP450 isozymes

  • Jin, Seong Eun;Ha, Hyekyung;Jeong, Soo-Jin;Shin, Hyeun-Kyoo
    • The Journal of Korean Medicine
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    • v.35 no.2
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    • pp.47-59
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    • 2014
  • Objectives: Most drug interactions are attributed to the inhibition or induction of the activity of cytochrome P450s (CYP450). Although the regulation of CYP450s by drugs has been widely reported, there have been few studies on influence of traditional herbal formulas on the drug-metabolizing enzymes. Because herbal formulas have been used traditionally to treat various diseases and because herb-drug interactions are crucial factors determining therapeutic efficacies, a systematic evaluation of the effects of herbal formulas is important. Methods: The effects of Galgeun-tang (GGT, gegen tang), Gumiganghwal-tang (GMGHT, jiuweiqianghuo tang), Insampaedok-san (ISPDS, renshenbaidu powder), Samsoeum (SSE, shensu drink), Socheongryong-tang (SCRT, xiaoqinglong-tang) and Sosiho-tang (SSHT, xiaochaihu tang) that are traditional herbal formulas used to treat common cold, on drug-metabolizing enzymes were evaluated through an in vitro CYP3A4, CYP2D6, CYP2C19 and CYP2E1 inhibition assay to assess its interaction potential with synthetic drugs. The inhibitory effects of herbal formulas were characterized with $IC_{50}$ values. Results: These six herbal formulas inhibited the activities of CYP3A4, 2C19, 2D6 and 2E1, in a concentration-dependent manner. Among the six herbal formulas, GGT critically inhibited CYP2C19, CYP2D6 and CYP2E1. GMGHT also inhibited CYP2D6 and CYP2E1 to a greater extent than the other CYP450 isozymes. Additionally, SSE and SSHT may change the effects of medicines that depend primarily on the CYP2C19 and CYP2E1 pathways. On the other hand, ISPDS and SCRT were not inhibited CYP3A4, CYP2C19, CYP2D6 and CYP2E1-mediated metabolism. Conclusions: These findings provide useful information regarding the safety and effectiveness of herbal formulas.

Effect of Ascorbic Acid Supplementation on Hepatic Microsomal and Mitochondrial Cytochrome P450 System in Diabetic Rats (비타민 C의 보강이 당뇨쥐의 간 소포체와 미토콘드리아의 Cytochrome P450계에 미치는 영향)

  • 정연재;임은영;김해리
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.4
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    • pp.682-688
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    • 1997
  • This study was performed to investigate whether ascorbic acid can modulate the induction of CYP2E1 and prevent the lipid peroxidation which may cause diabetic chronic complication. Diabetes was induced by intraperitoneal injection of streptozotocin to 5-week-old male Sprague-Dawley rats(150~170g). Normal and diabetic group was randomly divided into three groups each; Control(CON, no supplementation), SUP1 (50mg/d ascorbate supplementation) and SUP2(250mg/d ascorbate supplementation). Ascobic acid was prepared daily by dissolving in drinking water and supplied for 4 weeks. There was no difference in hepatic microsomal and mitochondrial P450 contents between normal and diabetes. Hepatic microsomal N-nitrosodimethylamine(NDMA) demethylase activity, which repre-sents contents of CYP2E1, was elevated in diabetes, but not significantly. The NDMA demethylase activity of diabetic SUP2 group was significantly lower activity than that of the diabetic CON group. However, no difference in hepatic mitochondrial NDMA demethylase activity was observed between the diabetes and the normal group. The result suggests that the induction of CYP2E1 in diabetes can be alleviated by ascorbic acid supplementation at the dose of 50mg1d. In addition, ascorbic acid supplementation showed dose-dependent reduction of hepatic microsomal TBARS contents in diabetic rats.

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Elicitor-InduciblePhytoalexin from Cell Suspension Cultures of Pepper(Capsicum annuum L.) (고추(Capsicum annuum L.) 배양세포의 Elicitor 유도성 Phytoalexin 생성)

  • 권순태;오세명
    • Journal of Life Science
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    • v.9 no.4
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    • pp.408-413
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    • 1999
  • Extracellular capsidiol, sesquiterpenoid phytoalexin, in the medium of pepper (Capsicum annuum L.) suspension cells was not identified from control cells, but highly accumulated in the elicitor-induced cells within 6 hours after the addition of 0.05$\mu\textrm{g}$/$m\ell$ cellulase. Capsidiol production in elicitor-induced cells was markedly suppressed by cytochrome P450 inhibitors, such as ancymidol and ketoconazole demonstrating that biosynthesis of capsidiol is catalyzed by at least on hydroxylation enzyme in the biochemical pathway. Based on protein electrophoresis, two bands, 23.0kDa and 27.5kDa, were identified as newly synthesized polypeptides in the elicitor-induced suspension cells, suggesting that pepper cells which were subjected to elicitor treatment activate specific gene(s) for capsidiol biosynthesis in cultured cells.

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Characterization of Pyribenzoxim Metabolizing Enzymes in Rat Liver Microsomes

  • Liu Kwang-Hyeon;Moon Joon-Kwan;Seo Jong-Su;Park Byeoung-Soo;Koo Suk-Jin;Lee Hye-Suk;Kim Jeong-Han
    • Toxicological Research
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    • v.22 no.1
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    • pp.1-8
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    • 2006
  • The primary metabolism of pyribenzoxim was studied in rat liver microsomes in order to identify the cytochrome P450 (CYP) isoform(s) and esterases involved in the metabolism of pyribenzoxim. Chemical inhibition using CYP isoform-selective inhibitors such as ${\alpha}$-naphthoflavone, tolbutamide, quinine, chlorzoxazone, troleandomycin, and undecynoic acid indicated that CYP1A and CYP2D are responsible for the oxidative metabolism of pyribenzoxim. And inhibitory studies using eserine, bis-nitrophenol phosphate, dibucaine, and mercuric chloride indicated pyribenzoxim hydrolysis involved in microsomal carboxylesterases containing an SH group (cysteine) at the active center.

Fabrication of Nanogap-Based PNA Chips for the Electrical Detection of Single Nucleotide Polymorphism

  • Park, Dae-Keun;Park, Hyung-Ju;Lee, Cho-Yeon;Hong, Dae-Wha;Lee, Young;Choi, In-Sung S.;Yun, Wan-Soo
    • Proceedings of the Korean Vacuum Society Conference
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    • 2012.02a
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    • pp.540-540
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    • 2012
  • Selective detection of single nucleotide polymorphism (SNP) of Cytochrome P450 2C19 (CYP2C19) was carried out by the PNA chips which were electrically-interfaced with interdigitated nanogap electrodes (INEs). The INEs whose average gap distance and effective gap length were about ~70 nm and ${\sim}140{\mu}m$, respectively, were prepared by the combination of the photo lithography and the surface-catalyzed chemical deposition, without using the e-beam lithography which is almost inevitable in the conventional lab-scale fabrication of the INEs. Four different types of target DNAs were successfully detected and discriminated by the INE-based PNA chips.

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Hepatoprotective Effect of Subfractions of Carthamus tinctorius L. Semen on the Reversal of Biotransformation Enzyme Activities in CCl4-induced Hepatotoxic Rats (사염화탄소로 유발된 간손상에서의 효소 활성도의 변화로 본 홍화자 분획물의 간손상 보호 작용)

  • 정춘식;정기화;정정숙
    • Journal of Food Hygiene and Safety
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    • v.14 no.2
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    • pp.172-178
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    • 1999
  • Previous studies have shown that methanol extract and its butanol fraction of Carthamus tinctorius L. Semen have the hepatoprotective effect on the CCl4-induced hepatotoxicity. The hepatoprotective effect of subfractions has been evaluated by analyzing blood and hepatocyte biochemical analyses and biotransformation enzyme analyses. Treatment of BS-5, subfraction has significantly decreased the activities of alanine aminotransferase and aspartate aminotransferase. In addition, the levels of cholesterol and triglyceride in liver have been decreased as compared with that of CCl4 treated rats. The hepatoprotective effect of BS-5, subfraction on the CCl4-induced hepatotoxicity would be mediated of the attenuation of the level of cytochrome P450 and the enhancement of the activity of glutathion S-transferase.

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Investigation of the Regulatory Effects of Saccharin on Cytochrome P450s in Male ICR Mice

  • Jo, Jun Hyeon;Kim, Sunjoo;Jeon, Tae Won;Jeong, Tae Cheon;Lee, Sangkyu
    • Toxicological Research
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    • v.33 no.1
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    • pp.25-30
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    • 2017
  • Saccharin, the first artificial sweetener, was discovered in 1879 that do not have any calories and is approximately 200~700 times sweeter than sugar. Saccharin was the most common domestically produced sweetener in Korea in 2010, and it has been used as an alternative to sugar in many products. The interaction between artificial sweeteners and drugs may affect the drug metabolism in patients with diabetes, cancer, and liver damage, this interaction has not been clarified thus far. Here, we examined the effects of the potential saccharin-drug interaction on the activities of 5 cytochrome P450 (CYPs) in male ICR mice; further, we examined the effects of saccharin (4,000 mg/kg) on the pharmacokinetics of bupropion after pretreatment of mice with saccharin for 7 days and after concomitant administration of bupropion and saccharin. Our results showed saccharin did not have a significant effect on the 5 CYPs in the S9 fractions obtained from the liver of mice. In addition, we observed no differences in the pharmacokinetic parameters of bupropion between the control group and the groups pretreated with saccharin and that receiving concomitant administration of saccharin. Thus, our results showed that saccharin is safe and the risk of saccharin-drug interaction is very low.

Identification and Partial Purification of Ethanol-Induced Hemoproteins in Human Liver (사람의 간에서 Ethanol에 의해 유발되는 hemoprotein들의 확인 및 부분정제)

  • Park, Sung-Woo;Seo, Bae-Seok;Jin, Kwang-Ho
    • Analytical Science and Technology
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    • v.8 no.2
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    • pp.117-124
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    • 1995
  • To Purify hemoproteins showing from 218nm absorbance, crude liver extract of human with hepatocirrhosis was treated with Triton N-101. Hemoproteins were purified by modification of Mohamed's method. This crude extract was applied to Octyl-Sepharose CL-4B column and the step elution was performed with 0.06% Lubrol PX and 0.25% Lubrol PX. The absorption of effluents were examined at 418nm and two peaks were appeared(Fig. 2). Hemoproteins were purified from Hyydroxyapatite and DEAE-Sephadex A-25 columns which the first peak was applied to(Fig. 3, 4). In death with suddenly, purified hemoproteins with 62 and 45kDa were obtained from 12.5% SDS-PAGE. In death with hepatocirrhosis, purified hemoprotein with 54kDa was obtainded from 12.5% SDS-PAGE(Fig. 5). Cytochrome P450 was purified to a specific content of 20.8nmol/mg protein with a recovery of about 4.1%. Absorbance maximum of these hemoproteins were 446nm at UV spectruum(Fig. 6).

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