• 한국환경생물학회:학술대회논문집
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• 한국환경생물학회 2001년도 학술대회
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• pp.103-104
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• 2001

• 약학회지
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• 제40권4호
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• pp.449-455
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• 1996

Betaine is one of the major water-soluble components in Lycii Fructus. In the present study the effect of repeated betaine treatment on the hepatotoxicity and the cytochrome P-4 50-dependent enzyme system was examined in adult female rats. Administrations of betaine (100 or 1,000mg/kg/day, ip) to rats repeatedly for 4 or 9 days did not evoke hepatotoxic response as determined by increases in glutamic pyruvic transaminase(GPT) and glutamic oxaloacetic transaminase(GOT) activities measured 24 hours following the final dose of betaine. The activities of aminopyrine N-demethylase, p-nitroanisole O-demethylase and p-nitrophenol hydroxylase as well as the contents of cytochrome P-450 were determined in hepatic microsomes of rats treated with betaine(1,000mg/kg/day, ip) for 4 or 9 days. Repeated treatment of rats with betaine for a period of 4 days induced a marginal decrease in the contents of cytochrome P-450, but did not influence the activities of p-nitrophenol hydroxylase, p-nitroanisole O-demethylase, or aminopyrine N-demethylase. Extension of the betaine treatment to 9 consecutive days failed to alter the parameters for hepatic drug metabolizing activity determined in the present study. Since repeated large doses of betaine were demonstrated to be tolerated by rats without showing any toxicity or changes in drug metabolizing enzyme activities in the liver, this compound appears to be relatively safe to animals upon long-term ingestion.

• Toxicological Research
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• 제9권2호
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• pp.177-186
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• 1993

Previous results from several laboratories have demonstrated that tumor necrosis factor-alpha (TNFalpha) depressed cytochrome P-450 (P-450)-dependent drug metabolism in vivo. However, there is some debate whether the action of TNFalpha is mediated by its direct effects on hepatocytes, or is indirectly mediated through the release of other mediators like IL-1 from macrophages. In the present studies, we investigated the effects of TNFalpha on P-450-dependent drug metabolizing enzyme as measured by 7-ethoxyresorufin O-deethylase (EROD) activity.

• 한국균학회지
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• 제31권1호
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• pp.34-39
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• 2003

싸리버섯 메탄올 추출물이 간독성 물질인 B$({\alpha})$P을 투여한 마우스에서 간 손상 억제 효과 및 cytochrome P-450 1A1 발현에 미치는 영향을 살펴보았다. B$({\alpha})$P 투여로 인한 혈청 ALT와 AST의 활성, 간 조직증의 lipid peroxide 함량, cytochrome P-450 함량, AD 및 AH 활성이 유의적으로 증가하였으며 싸리버섯 메탄올 추출물의 투여시 이들 활성 및 함량이 유의적으로 감소하였다. 반면, 간 조직중의 GSH 함량, GST, r-glutamylcysteine synthetase의 활성은 B$({\alpha})$P만 투여한 군에 비해 싸리버섯 메탄올 추출물을 투여시 증가하였다. 또한 immuno blotting 결과로부터 B$({\alpha})$P 투여에 의해 현저히 증가되었던 cytochrome P-450 1A1 isozyme 단백질 함량이 싸리버섯 메탄올 추출물의 투여로 감소됨을 확인하였다. 이와 같은 결과로부터 싸리버섯 메탄올 추출물은 B$({\alpha})$P에 의한 간 손상에 대한 보호 효과가 있는 것으로 사료된다.

• 약학회지
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• 제23권2호
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• pp.111-118
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• 1979

It was previously reported that cytochrome P$_{450}$ content in liver was increased when Capsicum acetone extract was given chronically to rats. The present study is aimed to investigate the effect of capsaicin, a principal component of red pepper, on the drug metabolizing enzymes in rat liver. Capsaicin (5mg/kg) was given intraperitoneally once a day for seven days and zoxazolamine paralysis time and hexobarbital sleeping time were determined 24 hrs after the last dose of capsaicin. Plasma hexobarbital concentration was also determined five and 15 min after hexobarbital administration to rats. Zoxazolamine paralysis time and hexobarbital sleeping time were shortened by 31.6% and 37.1%, respectively, compared with control group. Plasma hexobarbital concentration was lowered by 26.2% after five min and by 35.2% after 15 min, respectively, compared with control group. However, administration of single dose of capsaicin did not affect the zoxazolamine paralysis time and hexobarbital sleeping time. Microsomal cytochrome P$_{450}$ content and NADPH-cytochrome C reductase activity were increased by 14.6% and 11.6%, respectively in the rats pretreated with capsaicin for seven days, while cytochrome b$_{5}$ content was not changed. These results suggest that treatment with capsaicin for seven days may induce the drug metabolizing enzyme in rat liver.

• BMB Reports
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• 제38권3호
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• pp.366-369
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• 2005

NADPH-cytochrome P450 reductase (CPR) transfers electrons from NADPH to cytochrome P450 and also catalyzes the one-electron reduction of many drugs and foreign compounds. Various spectrophotometric assays have been performed to examine electron-accepting properties of CPR and its ability to reduce cytochrome $b_5$, cytochrome c, and ferricyanide. In this report, reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) by CPR has been assessed as a method for monitoring CPR activity. The principle advantage of this substance is that the reduction of MTT can be assayed directly in the reaction medium by a continuous spectrophotometric method. The electrons released from NADPH by CPR were transferred to MTT. MTT reduction activity was then assessed spectrophotometrically by measuring the increase of $A_{610}$. MTT reduction followed classical Michaelis-Menten kinetics ($K_m\;=\;20\;{\mu}M$, $k_{cat}\;=\;1,910\;min^{-1}$). This method offers the advantages of a commercially available substrate and short analysis time by a simple measurement of enzymatic activity of CPR.

• 동의생리병리학회지
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• 제22권1호
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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.

• 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.

• 농약과학회지
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• 제9권4호
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• pp.338-346
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• 2005

Carbendazim의 랫드 간 해독체계에 대한 영향을 검색하기 위하여 간장독성의 지표 효소인 혈장 ALT(alanine aminotransferase) 및 AST(aspartate aminotransferase) 활성, 간에 대한 독성, 해독 및 대사에 대한 영향을 구명하기 위하여 간 GSH(glutathione), GST(glutathione-S-transferase), cytochrome P450 및 cytochrome P450 reductase 활성을 375, 750, 1,500 mg/kg 약량에서 측정한 결과 혈장 ALT 및 AST 활성이 120분 후에 약간의 증가가 있었으나 특이한 독성증상은 관찰되지 않았다. GSH는 고농도와 중농도 120분에서 20%의 함량증가가 있었고, GST는 120분까지 $36{\sim}50%$ 정도의 활성저해가 있었으나 240분에는 활성이 회복되었다. Cytochrome P450함량은 60분까지 $25{\sim}50%$까지 함량이 저하되었으나 120분에 70%이상 회복되었고, 240분 저농도에서는 거의 회복되었으며, cytochrome P450 reductase도 120분까지 $25{\sim}50%$ 활성저해가 있었으나, 240분에는 무처리 군의 활성과 유사하게 회복되어 대사관련 효소에 대한 손상은 크지 않을 것으로 판단되었다. 이상의 결과에서 benzimidazole 계 살균제인 carbendazim은 생체내 해독 및 대사관련 체계에 영향이 적은 농약으로 급성적인 중독은 일으키지 않을 것으로 판단되었다.

• BMB Reports
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• 제37권5호
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• pp.629-633
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• 2004

NADPH-cytochrome P450 reductase (CPR) transfers electrons from NADPH to cytochrome P450, and catalyzes the one-electron reduction of many drugs and foreign compounds. Various forms of spectrophotometric titration have been performed to investigate the electron-accepting properties of CPR, particularly, to examine its ability to reduce cytochrome c and ferricyanide. In this study, the reduction of 1,1-diphenyl-2-picrylhydrazyl (DPPH) by CPR was assessed as a means of monitoring CPR activity. The principle advantage of DPPH is that its reduction can be assayed directly in the reaction medium by a continuous spectrophotometry. Thus, electrons released from NADPH by CPR were transferred to DPPH, and DPPH reduction was then followed spectrophotometrically by measuring $A_{520}$ reduction. Optimal assay concentrations of DPPH, CPR, potassium phosphate buffer, and NADPH were first established. DPPH reduction activity was found to depend upon the strength of the buffer used, which was optimal at 100 mM potassium phosphate and pH 7.6. The extinction coefficient of DPPH was $4.09\;mM^{-1}\;cm^{-1}$. DPPH reduction followed classical Michaelis-Menten kinetics ($K_m\;=\;28\;{\mu}M$, $K_{cat}\;=\;1690\;min^{-1}$). This method uses readily available materials, and has the additional advantages of being rapid and inexpensive.