• 제목/요약/키워드: P450 3A4

검색결과 616건 처리시간 0.035초

ROLES OF HUMAN LIVER CYTOCHROMES P450 3A4 AND 1A2 IN THE OXIDATION OF MYRISTICIN

  • Yun, Chul-Ho;Lee, Hye-Suk;Lee, Hee-Yong;Yim, Sung-Kun;Kim, Keon-Hee;Yea, Sung-Su
    • Proceedings of the PSK Conference
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.137.1-137.1
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    • 2003
  • Myristicin, 1-allyl-3, 4-methylenedioxy-5-methoxybenzene, is a naturally occurring alkenylbenzene compound. It is found in nutmag, mace, parsley, carrot, black pepper, many natural oils and flavoring agents. The aim of this work was to identify the form(s) of human liver cytochrome P450 (P450) involved in the hepatic transformation of myristicin to its major metabolite, 5-allyl-1-methoxy-2, 3-dihydroxybenzene (M1). (omitted)

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The Toxicity of Fthalide in Rats (흰쥐에 있어서 Fthalide의 독성)

  • 김영찬;장영수
    • YAKHAK HOEJI
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    • 제39권4호
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    • pp.450-460
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    • 1995
  • The acute toxicity of fthalide in rat was studied in vivo by the observations of the changes in hematogram, serological parameters, content of cytochrome p-450, activities of NADPH-cytochrom c reductase, glucose-6-phosphatase, and the contents of cholinesterase and carboxylesterase in liver. Fthabde is a practically non-toxic substance(LD50 is 3.86g/kg), but rats were intoxicated with fthabde at a oral dose of 100 mg/kg for 12 days. WBC were significantly decreased and activities of ALT and LDH, on the cotrary, the content of glucose in serum were slightly increased. Cytochrome p-450 and lipid peroxide in liver were significantly increased in the fthalide-intoxicated rats. The longer administration of fthalide showed further increase of carboxylesterase activity in liver and serum, but decrease of activities of glucose-6-phosphatase and cholinesterase in liver and serum. These results show that fthatide can induce the hepatocellular injury and neurotoxicity.

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Reduction of Phosphorus Fertilizer in Mulberry Fields, High in Phosphate (인산축적 뽕밭의 인산 감량시비에 관한 연구)

  • 이원주;최영철
    • Journal of Sericultural and Entomological Science
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    • 제35권1호
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    • pp.11-16
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    • 1993
  • Field experiment and silkworm rearing were conducted for 4years in an attempt to reduce phosphorus fertilizer in mulberry field with high levels of phosphate. Experiments consisted of four treatments; normal recommended P application(13kg P2O5/10a), half, null and no fertilizer on each of 3 mulberry fields, two fields with 300ppm and one filed begining with 450ppm of aviable P2O5 content in soil. One of 300ppm fields was used for leaf quantity and one for leaf quality test by silkworm rearing. Leaf yield in the 300ppm field decreased after the 3rd spring in the no phosphorus treatment and in the 4th fall in the half phosphorus treatment. No yield decrease occurred in 450ppm field for 4 years. Yield decrease did occur in the next rearing season after soil phosphate content in the 10~20cm zone dropped below 150ppm. Phosphorus fertilizer should be applied at this time. Though P2O5 concentration in leaves of no phosphorus treatment was 0.18% lower that that of conventional treatment, there were no difference in cocoon quality.

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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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    • 제34권1호통권132호
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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.

Modulation of human cytochrome P450 1B1 by 2,3',4,5'-tetramethoxystilbene(TMS) in mammary tumor cells and its application for cancer chemotherapy

  • Lee, Sang-Kwang;Kim, Sanghee;Kim, Mie-Young;Chun, Young-Jin
    • Proceedings of the Korean Society of Toxicology Conference
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    • 한국독성학회 2003년도 춘계학술대회 논문집
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    • pp.77-77
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    • 2003
  • We have previously shown that 2, 3' , 4, 5' -tetramethoxystilbene(TMS), a trans-stilbene analogue, is one of the most potently selective inhibitor of recombinant human cytochrome P450 1B1 in vitro. In the present studies, the effects of TMS on the expression of cytochrome P450 1B1 were investigated in human mammary cell lines such as MCF-7 and MCF-10A. (omitted)

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Modulation of Cytochrome P450 1B1 Expression by A Stilbene Analog and its Effect on the Sensitivity to Anticancer Agents in Human Cancer Cells.

  • Lee, Sang-Kwang;Park, Sung-Sik;Kim, Mie-Young;Chun, Young-Jin
    • Proceedings of the PSK Conference
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.209.1-209.1
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    • 2003
  • We have previously shown that 2, 3', 4, 5' -tetramethoxystilbene(TMS) from synthetic trans-stilbene analogues, is one of the most potently selective inhibitor of recombinant human cytochrome P450 1B1 in vitro. In the present studies. the effects of TMS on the expression of cytochrome P450 1B1 were investigated in human cancer cell lines such as MCF-7 and HL -60. TCDD-stimulated P450 1B1 protein and mRNA expression was significantly suppressed by TMS in a dose-dependent manner. (omitted)

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Pharmacodynamic and pharmacokinetic interactions between herbs andwestern drugs

  • Lee, Ju-Young
    • Advances in Traditional Medicine
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    • 제8권3호
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    • pp.207-214
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    • 2008
  • In recent years, the combined use of Herbal medicines and Western drugs has been increasing. Though certain problems may occur when both types of medicines are taken together, they havenot been adequately analyzed. It was reported that anticoagulation was enhanced in addition tobleeding when patients took long-term warfarin therapy in combination with Salvia miltiorrhiza(danshen), and laxative herbs accelerate intestinal transit and interfere with the absorption. Herbal constituents, curcumin, ginsenosides, piperine, catechins and silymarin were found to beinhibitors of P-glycoprotein. St John's wort induces the intestinal expression of P-glycoprotein. Anthraquinone, quercetin and coumarins were found to be a potent inhibitor of P-450. Glycyrrhizin or liquorice extracts, Garlic and St John's wort are a potent inducer of CYP3A4. This review provides a critical overview of interactions between herbal medicines and other drugs. Hence, it is necessary to study the pharmacodynamic and pharmacokinetic interactions of many herbal medicines between western drugs.

In Vitro Pharmacological Characteristics of SKP-450, A Novel $K^+$ Channel Opener, in Non-Vascular Smooth Muscles in Comparison with Levcromakalim (비-혈관평활근에서 새로운 $K^+$ 통로 개방제인 SKP-450의 약리학적 작용의 특성-Levcromakalim의 작용과 비교)

  • Park, Ji-Young;Kim, Hyun-Hee;Yoo, Sung-Eun;Hong, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • 제1권6호
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    • pp.759-767
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    • 1997
  • In the present study, we characterized the non-vascular smooth muscle relaxant effects of a novel benzoyran derivative ,SKP-450 (2-[2'(1',3'-dioxolone)-2-methyl-4- (2'-oxo-1'-pyrrolidinyl) -6-nitro-2H-1- benzopyran) and its metabolite, SKP-310, in comparison with levcromakalim (LCRK). In the rat stomach fundus, the spontaneous motility stimulated by $10^{-6.5}\;M$ bethanechol was completely eliminated not only by $10^{-7}\;M$ SKP-450 but also by $10^{-6}\;M$ LCRK, which were blocked by $10^{-6}\;M$ glibenclamide. The inhibitory effect of SKP-450 $pD_2,\;3.94{\pm}0.66)$ was much less than LCRK $(pD2,\;5.73{\pm}0.38,\;p<0.05)$. In the bethanechol $(10{-6.5 }\;M)-stimulated$ urinary bladder, the tonus was decreased in association with elimination of spontaneous motility by $10^{-7}\;M$ M SKP-450 and $10^{-6}\;M\;LCRK\;(pD2,\;6.77{\pm}0.06)\;(P<0.05)$, which were inhibitable by $10^{-6}\;M$ glibenclamide. The inhibitory effect of SKP-450 $(pD2,\;7.66{\pm}0.05)$ was significantly more potent than that of LCRK $(pD2,\;6.77{\pm}0.06,\;p<0.05)$. In the rat uterus stimulated by $PGF_{2\alpha}\;(10^{-7}\;M)$, both increased tonus and spontaneous motility were eliminated by $10^{-6}\;M$ LCRK with slight depression of the tonus, but not by SKP-450 $(10^{-5}\;M)$. The stimulated trachea of guinea-pig by $10^{-6.5}\;M$ bethanechol was moderately suppressed by SKP-450 $(10^{-6}{sim}10^{-5}\;M)$ but little by SKP-310. In association with the relaxant effects, SKP-450 $(10^{-6}\;M)$ and LCRK $(10^{-5}\;M)$ caused a significant stimulation of the $^{86}Rb$ efflux from rat urinary bladder and stomach fundus, which were antagonized by $10^{-5}\;M$ glibenclamide, whereas the $K^+$ channel openers could not exert a stimulation of the $^{86}Rb$ efflux from rat uterus. In conclusion, it is suggested that SKP-450 exerts potent relaxant effects on the urinary bladder detrusor muscle and duodenum, whereas it shows much less effect on stomach fundus and uterus as contrasted to LCRK.

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Cytochrome P450 1 gene in Eel, Anguilla japonica: cloning and expression patterns after exposure to benzo[a]pyrene (뱀장어(Anguilla japonica)에서 Cytochrome P450 1 gene 클로닝 및 benzo[a]pyrene 노출에 따른 발현 분석)

  • Jo, Hyun Ho;Kim, Ju An;Lee, Seung Hyun;Chung, Joon Ki
    • Journal of fish pathology
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    • 제33권2호
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    • pp.153-161
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    • 2020
  • Cytochrome P450(CYP) gene is involved in the biotransformation of drugs and environmental pollutants. In this study, we analyzed the nucleotide sequence of the Anguilla japonica CYP1(AjCYP1) family gene and examined the relative expression of AjCYP1A, AjCYP1B and AjCYP1C1 in response to the exposure to environmental pollutants. After exposure to B[a]P 20mg/kg bw, the expression of AjCYP1 family gene increased over time. Among four tissues examined (liver, spleen, gill and kidney), AjCYP1 family gene was expressed significantly in the kidney. Compared with the control group, AjCYP1A was expressed about 5-fold at 48 hr, AjCYP1B about 6-fold at 24 hr, and AjCYP1C1 about 4-fold at 24 hr. However, after exposure to B[a]P 200mg/kg bw, AjCYP1A did not change in all tissues. On the other hand, AjCYP1B was expressed at about 4-fold at 24 hr in the spleen and 4-fold at 48 hr in the gill. Finally AjCYP1C1 was expressed 3.7-fold and 4.3-fold in the spleen and kidneys at 48 hr, respectively. Taken together, our results suggest that the expression of AjCYP1 gene in eel tissues might be used as a useful tool to assess the exposure to environmental pollutants in aquaculture system.

Cytochrome P-450 3A4 proximal promoter activity by histone deacetylase inhibitor in HepG2 cell.

  • Kim, Ja-Young;Ahn, Mee-Ryung;Sheen, Yhun-Yhong
    • Proceedings of the PSK Conference
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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    • pp.120.2-120.2
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    • 2003
  • Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this is detoxification and metabolizing more than 50% clinical drugs in use. Expression of CYP3A4 is transciptionally regulated by the Pregnenolone X receptor (PXR), of which human form is Steroid and Xenobiotics receptor (SXR). SXR is activated by wide range of endogenous and exogenous compounds, and then induces CYP3A4 gene expression. In the previous study, it has been known that proximal promoter (-864 to +64) does not response to chemical inducers such as pregnenolone 16a-carbonitrile (PCN), Rifampicin, Estrogen in terms of transcription of CYP 3A4 in cultured cells. (omitted)

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