• Journal of Life Science
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• v.8 no.6
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• pp.695-701
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• 1998

This study was carried out to investigate levels of the components of microsomal mixed function oxidase (MFO) system and activities of the hepatic microsomal cytochrome P45O (P45O)-dependent monooxygenases of grass snake (Natrix tigrina Lateralis) and to compare with those of rat. The levels of P45O and cytochrome b$_{5}$, (b$_{5}$) of snake were much lower than those in rat. NADPH-cytochrome c reductase activity in the snake was also only 40% of that in the rat. Activities of 7-ethoxycoumarin 0-deethylase (ECOD) and benzphetamine N-demethylase (BPDM) of snake hepatic microsomes, when compared with those of rat, were markedly low. But, aryl hydrocarbon hydroxylase (AHH) and testosterone hydroxylase (TSH) activities were nearly the same or higher than those of the rat. Of the P45O-dependent TSHs measured, 7$\alpha$-hydroxylase activity was the highest in snake, whereas, 6$\beta$-hydroxylase activity was the highest in rat. However, stereoselectivity of the enzyme from the snake to C2 and C6 positions of testoste-rone was the same as rat. The result of radioimmunoassay (RIA) for the identification of five P45O isozymes with MAbs shows that relatively high content of ethanol-inducible P45O isozyme, CYP2El, exists in the rat, whereas MC-inducible P45O isozyme, CYP2A1/1A2, does in the snake. From the analyses of SDS-PAGE and RIA of partially pu-rified P45O, we suggest the possibility of the presence of a certain P45O isozyme(s) in hepatic microsomes of snake different from those of rat.

• Archives of Pharmacal Research
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• v.25 no.2
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• pp.197-201
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• 2002

${\beta}-lonone$ has been reported to induce the cytochrome P45O (P45O) 2B1 in rats. In this study, the effects of ${\beta}-ionone$ and an isomer, ${\alpha}-ionone$, on liver P45O IA and 2B expression in Sprague Dawley rats were investigated . Subcutaneous administration of ${\alpha}-$ and ${\beta}-lonone$ 72 and 48hr prior to sacrificing the animals induced the liver microsomal P45O 1A and 2B proteins. P45O 2Bl induction was associated with the accumulation of its corresponding mRNA. 1 Induction by ${\beta}-lonone$ was much higher than that by ${\alpha}-ionone$-ionone in both the mRNA and protein levels. When the route of administration was compared, P45O 2B was induced more strongly after oral administration compared to that after subcutaneous injection. A single oral dose of 100, 300 and 600 mg/kg of ${\alpha}-$ and ${\beta}-lonone$ for 24 h induced P45O 2B1 -selective pentoxyresorufin Odepentylase activity comparably in a dose-dependent manner In addition, ${\alpha}-$ and ${\beta}-lonone$ induced the P45O 1A and 2B proteins. These results suggest that ${\alpha}-$ and ${\beta}-lonone$ might be potent P45O 2Bl inducers in rats, and that both ionones may be useful for examining the role of metabolic activation in chemical-induced toxicity where metabolic activation is required.

• Korean Journal of Pharmacognosy
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• v.38 no.1
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• pp.62-66
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• 2007

Ethanol extract from Salvia miltiorrhiza (SME) was tested for breast cancer chemoprevention and metastasis by measuring the activites of cytochrome P45O 1A1, aromatase, ornithine decarboxylase (ODC), and matrix metalloproteinase (MMP)-9. SME significantly inhibited cytochrome P45O 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity in a dose-dependent manner in a concentration range of 100${\sim}$l,200 ${\mu}g/ml$ (p<0.01). Microsomal aromatase (estrogen synthase) activity was suppressed 54.9%${\sim}$77.5% by the SME at concentration of 600${\sim}$l,200 ${\mu}g/ml$. ODC activity induced by 12-O-tet-radecanoylphorbol-13-acetate (TPA) was significantly reduced by the SME 900 and 1,200 ${\mu}g/ml$ (p<0.05) in MCF-7 breast cancer cells. In addition, SME (900 and 1,200 ${\mu}g/ml$) markedly inhibited MMP-9 activity, a key role in cancer metastasis. Therefore, SME is worth further investigation with respect to breast cancer chemoprevention or therapy.

• Korean Journal of Pharmacognosy
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• v.34 no.2 s.133
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• pp.161-165
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• 2003

Ethanol extract from Thesium chinense Tunczaninov (TCTE) was tested for breast cancer chemopreventive activity by measuring 7,12-dimethylbenz[a]anthracene (DMBA) - induced cytochrome P450 1A1 activity, induction of quinone reductase and glutathione S-transferase, and glutathione level. TCTE significantly inhibited cytochrome P45O 1A1 activity at the concentration of 90 and 150 mg/ml. TCTE induced quinone reductase activity in a dose-dependent manner in a concentration range of 3-150 mg/ml. In addition glutathione S-transferase activity and glutathione level were increased with TCTE in cultured murine hepatoma Hepa1c1c7 cells. These results suggest that TCTE has breast cancer chemopreventive potential by inhibiting cytochrome P45O 1A1 activity, inducing quinone reductase and glutathione S-transferase activities, and increasing GSH level.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.05a
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• pp.75-75
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• 2002

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.135.2-136
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• 2002

• YAKHAK HOEJI
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• v.44 no.4
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• pp.300-307
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• 2000

Expression of xenobiotic-metabolizing enzymes can be altered by xenobiotics, which represents changes in the production of reactive metabolic intermediates as well as toxicities in tissues. Metabolic intermediates derived from xenobiotics are considered to produce the reactive oxygen species including drug free radicals and hydroxyl free radicals, which would be ultimately responsible for drug-induced toxicities. The effects of 1,2-benzothiazine anti-inflammatory agents on the expression of xenobiotic-metabolizing enzymes including major cytochrome P450s, microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) were studied in the liver with the aim of providing the part of information on potential production of reactive metabolites and hepatotoxicity by the agents. The synthetic compounds 24, 36 and 39 exhibited anti-inflammatory effects in rats as assessed by the Randall-Selitto method. The anti-inflammatory effect was detected as early as at 30 min after gavaging the agents with the ED5O being noted at 80 mg/kg, which was comparable to that of ibuprofen. Treatment of rats with each compound (100 mg/kg, 3d) resulted in no significant induction in the immunochemically-detectable cytochromes P45O 1A1/2, P450 2B1/2, P45O 2 Cl1 and P45O 2El. Changes in the mEN expression were also minimal, as evidenced by both Western blot and Northern blot analyses. Hepatic GST expression was slightly increased by the agents: GST Ya protein and mRNA expression was ～1.5-fold increased after treatment with compounds 24 and 39, whereas GST Yb1/2 and Yc1/2 mRNA levels were elevated 2- to 3-fold. In summary the effects of the synthetic 1,2-benzothiazines on the expression of major P45O, mEH and G57 were not significant, providing evidence that metabolic activation of the agents, potential drug interaction and hepatotoxicity would be minimal.

• Archives of Pharmacal Research
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• v.19 no.6
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• pp.514-519
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• 1996

In order to understand the mechanism of action of flavonoids on the drug metabolizing enzyme, cytochrome P450IA1, this study was undertaken to examine the effect of chrysin, morin, myricetin and aminopyrine on the activities of ethoxyresorufin O-deethylase and benzo(.alpha.) pyrene hydroxylase in the liver. In the isolated perfused rat liver that was pretreated with 3-methylcholanthrene (3MC), chrysin, morin, myricetin and aminopyrine inhibited the activity of ethoxyresorufin O-deethylase with concentration dependent manner. The isolated liver perfusion with chrysin, morin, myricetin and aminopyrine showed inhibition on the induction of ethoxyresorufin O- deethylase by 3MC. And also, in mouse liver hepa I cells, 3MC-stimulated the benzo(.alpha.)pyrene hydroxylase activity which was inhibited by chrysin, morin, myricetin and aminopyrine. These results strongly suggested that hydoxylated flavonoids interfered not only the induction of cytochrome P45OIA1 enzymes by 3MC but also the interaction of substrates and enzyme.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.100-100
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• 1993

Antiestrogen은 에스트로젠 의존성 유방암 치료에 사용되는 약물로써 표적 세포 내에서 에스트로젠 수용체와 작용하여 세포 증식 억제 작용을 나타내고 동시에 에스트로젠 수용체와는 구분되는 소포체 분획의 antiestrogen specific binding site (AEBS) 와도 결합을 하는 것으로 알려져 있다. 그러나, 아직 이 AEBS의 생리적 또는 약리적 기능은 밝혀져 있지 않다. 따라서 본 실험에서는 AEBS의 기능을 조사하기 위하여 cytochrome P45O III 효소군과 AEBS와의 관계를 자옹 백서를 이용하여 면역 화학 반응 실험 및 경쟁적 결합 반응 실험을 하였고, 그 결과는 다음과 같다. 1) AEBS에 대해서 SKF-525A와 metyrapone은 결합 능력을 나타내었다. 2) 자성쥐에서는 주령이 증가함에 따라 cytochrome P450양이 감소하였다. 3) 자옹성쥐 모두에서 phenobarbital 처치에 의해 cytochrome P450 III 효소양이 증가하였고, AEBS도 증가하였다. 4) 웅성쥐에서는 testosterone에 의하여 AEBS가 증가하였다. 5) 자웅성쥐 모두에 tamoxifen 관류시 cytochrome P450 III 효소양이 증가하였고 estradiol과 병용 관류시에는 tamonifen 단독 관류시보다 감소하였다. 이상의 결과에서 tamoxifen이 cytochrome P450 III을 유도할 수 있는 것으로 사료되며 cytochrome P450 III 효소군과 안티에스트로젠 결합부위와 밀접한 관련이 있는 것으로 생각된다.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.142.1-142.1
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• 2002