• Korean Journal of Acupuncture
• /
• 제19권2호
• /
• pp.57-61
• /
• 2002

천궁약침액을 7일간 중완혈, 간수혈 및 임의혈에 투여한 후 마우스의 간에서 유도되는 phase I enzyme 억제 효과를 살펴본 결과 천궁 약침액은 CYP 1A1를 저해하였고, 생체의 CYP 2E1의 활성도 억제하였으므로 천궁 약침액은 암예방 효과가 있을 것으로 사료된다.

• 한국환경성돌연변이발암원학회지
• /
• 제16권2호
• /
• pp.97-102
• /
• 1996

In this study, we have quantified genotype frequency of the cytochrome P450 (P450) 2E1 which codes for the P450 enzyme primarily responsible for the metabolic activation of carcinogenic nitrosamines and low molecular organic solvents, in Korean population by using PCR and RFLP at two sites previously associated with some cancers; a PstI and RsaI RFLP in the transcriptional regulatory region of the human P450 2E1 gene. The genotype frequencies of homozygous wild type (PstI site-absent) and heterozygous mutant type (PstI site-present) in PstI RFLP were 0.70 and 030, respectively. The homozygous mutant type in Pstl RFLP was not observed in Korean population. The genotype frequencies of homozygous wild type (RsaI site-present), heterozygous mutant type (RsaI site-absent), and homozygous mutant type in RsaI RFLP were 0.71, 0.26, and 0.03, respectively.

• 한국식품위생안전성학회지
• /
• 제11권4호
• /
• pp.291-297
• /
• 1996

The role of cytochrome P-450 2E1 (P450 2E1) in the early phase of alcoholic fatty liver was examined. Female rats were pretreated with either allyl sulfide (200 mg/kg, po), disulfiram (500 mg/kg, po), YH 439 (250 mg/kg, po) or pyrazine (200 mg/kg/day$\times$2 days, ip). Marked changes in carbon tetrachloride-induced hepatotoxicity and caboxyhemoglobin (COHb) elevation due to dichloromethane administration were observed in rats treated with one of the P450 2E1 modulators. A single dose of ethanol (6 g/kg, po) increased the hepatic triglyceride contents approximately 2 fold, which was inhibited completely by YH 439 pretreatment. However, the other P450 2E1 modulators failed to alter the ethanol-induced hepatic triglyceride accumulation. In vitro hepatic microsomal enzyme activity was determined in 4 week old premature and 12 week old adult rats. Aminopyrine-N demethylation was not different, but p-nitrophenol hydroxylation and p-nitroanisole O-demethylation were significantly higher in premature rats. However, no difference in the triglyceride accumulation induced by an intraperitoneal dose of ethanol (3 g/kg) was noted between premature and adult rats. The results suggest that the P450 2E1 activity dose not play an important role in the induction of acute alcoholic fatty liver.

• BMB Reports
• /
• 제30권1호
• /
• pp.73-79
• /
• 1997

This study was designed to investigate the effects of dietary garlic powder on cytochrome P450 enzymes and membrane stability in murine hepatocarcinogenesis initiated by diethylnitrosamine (DEN). Male Sprague-Dawley rats received a single intraperitoneal injection of DEN (200 mg/kg body wt) dissolved in saline. After 2 weeks on a basal diet, animals were fed diets containing 0. 0.5. 2.0. or 5.0% garlic powder for 6 weeks, and were subjected to two-thirds partial hepatectomy. The areas of placental glutathione S-transferase (GST-P) positive foci were inhibited in rats fed with garlic diets. GST-P is the most effective marker for DEN-initiated lesions. Hepatic microsomal lipid peroxidation was significantly decreased in rats fed with 2.0 and 5.0% garlic powder diets compared with that observed in the control animals and hepatic microsomal glucose 6-phosphatase (G6Pase) activity was found to increase significantly in rats fed 0.5 and 2.0% garlic powder diets. Thus as little as 0.5% garlic powder has a positive effect on the stability of hepatic microsomal membranes. p-Nitrophenol hydroxylase (PNPH) activity and the level of cytochrome P450 2E1 protein in the hepatic microsomes from rats fed diets containing 2.0 and 5.0% garlic powder were much lower than those of control microsomes. Rats fed 5.0% garlic powder diets exhibited the lowest P450 2E1 activity and protein levels among groups. Pentoxyresorufin O-dealkylase activity and immunoblot (cytochrome P450 2B1) analyses were not different between groups. However, the levels of cytochrome P450 1A1/2 protein in rats fed 0.5 and 2.0% garlic powder were significantly induced compared to controls. These results suggest that 2.0% garlic powder is effective in inhibiting the areas of GST-P positive foci, modulating certain isoforms of cytochrome P450 enzymes and stabilizing the hepatic microsomal membrane. Thus, the selective modification of cytochrome P450 enzymes and membrane stability by dietary garlic powder may influence areas of GST-P positive foci and chemoprevention of post-initiation of rat hepatocarcinogenesis.

• Toxicological Research
• /
• 제12권2호
• /
• pp.155-161
• /
• 1996

The enzymatic properties for NADPH-P450 reductase domain of a fusion protein between human cytochrome P450 1A1 and rat NADPH-P450 reductase expressed in Escherichia coli were investigated. The fusion plasmid pCW/1A1OR-expressed E. coli membrane showed high NADPH-cytochrome c reductase activity ($830.1\pm 85.8 nmol\cdot min^{-1}\cdot mg protein^{-1}$), while pCW control vector and P 450 1A1 expression vector pCW/1A1 showed relatively quite low activity ($4.35\pm 0.49, 3.27\pm 0.50 nmol\cdot min^{-1}\cdot mg protein^{-1}$, respectively). The kinetic curves for NADPH-cytochrome c reductase followed typical Michaelis-Menten kinetics. The $K_{max}$ and $V_{max}$ for NADPH-dependent reductase activity were $8.24\pm 2.61\mu $and $817.9\pm 60.8 nmol\cdot min^{-1}\cdot mg protein^{-1}$, respectively, whereas those for cytochrome c-dependent reductase activity were $19.97\pm 2.86\mu M$ and $1303.5\pm 67.1 nmol\cdot min^{-1}\cdot mg protein^{-1}$. The reductase activities were also compared with those of rat, porcine and human liver microsomes. The activity of pCW/ 1A1OR-expressed E. coli membrane was 15.2-fold higher than that of rat liver microsome. Treatment with benzo(a)pyrene, 7-ethoxyresorufin and $\alpha$-naphthofiavone which are known as specific substrates or inhibitor for human P450 1A1 increased NADPH-cytochrome c reductase activity of fusion protein in E. coli membrane dose-dependently. These results demonstrate that the membrane topology of fused enzyme may be important for activity of its NADPH-P450 reductase domain.

• Archives of Pharmacal Research
• /
• 제18권3호
• /
• pp.179-182
• /
• 1995

Previous study showed that $CCl_4$ administration evoked a rapid decrease in cytochrome $P_{450}$ 2E1 protein soon after the exposure due to posttranslational inhibition(Biochem. Biophys. Res. Commun. 179:449-454, 1991). In this report, aniline hydroxylase and the amounts of immunoreactive $P_{450}$ 2E1 were rapidly decreased during day 1 to 2 and recovered during day 3 to 4 after a single dose of $CCl_4$. The activity of pentoxyresorufin-O-dealkylase was also suppressed at day 1 and began to repair from day 2. However, the decrease in immunoreactive $P_{450}$ 2C content was not observed. The decreases in $P_{450}$ 2E1 enzyme activity and immunoreactive protein by acute $CCl_4$ treatment were accompanied by a decline in $P_{450}$ 2E1 mRNA level. The data thus suggested a pretranslational reduction of $P_{450}$ 2E1 during day 1 to 2 after acute $CCl_4$ treatment.

• 농약과학회지
• /
• 제2권2호
• /
• pp.10-15
• /
• 1998

Carbofuran 및 N-dimethoxyphosphinothioyl carbofuran (PSC)의 AChE에 대한 이분자 저해 속도상수(bimolecular inhibition rate constant, $k_{i}$)를 관찰하였다. Carbofuran은 $7.7{\times}10^{5}\;M^{-1}{\cdot}min^{-1}$으로 높은 저해효과를 보이고 있는 반면, PSC는 $1.2{\times}10^{3}\;M^{-1}{\cdot}min^{-1}$으로 carbofuran에 비하여 AChE에 대한 저해력이 600배 정도 낮은 저해력을 갖고 있는 것으로 관찰되어 독성발현을 위하여 활성화 과정이 필요한 것으로 확인되었다. AChE/mixed function oxidase(mfo) coupling system을 이용한 microsomal oxidative activation 실험에서 PSC의 AChE에 대한 저해력이 control에 비하여 NADPH가 첨가된 oxidase 처리구에서 800배 더 강하게 나타났으며, cytochrome $P_{450}$의 저해제를 첨가한 oxidase+PBO 처리구에서는 control의 저해 경향과 유사하였다. 또한 생쥐 뇌 AChE에 대한 PSC의 $I_{50}$은 28 mg/kg인 반면 PBO를 전처리하였을 경우 $I_{50}$은 57 mg/kg으로 나타나 cytochrome $P_{450}$ 저해제로 인하여 PSC의 저해력이 2배정도 감소된 것을 관찰할 수 있었고, PSC는 독성발현을 위하여 활성화 과정을 거쳐야 하며, 이 과정에서 cytochrome $P_{450}$ 이 작용함을 확인할 수 있었다. PSC와 MCPBA를 반응시켜 산화 과정을 통하여 생성된 독성대사물을 분석한 결과 반응산물의 약 55%가 carbofuran임을 확인할 수 있었다. 본 연구를 통하여 PSC의 활성화 과정을 통한 독성발현에 cytochrome $P_{450}$이 중요한 역할을 하는 효소임을 확인할 수 있었고, PSC의 산화적 활성화 과정을 통한 주된 독성대사물이 carbofuran임을 확인할 수 있었다.

• 동의생리병리학회지
• /
• 제22권1호
• /
• pp.155-161
• /
• 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.

• 사상체질의학회지
• /
• 제24권4호
• /
• pp.84-91
• /
• 2012

Objectives : The purpose of this study is to investigate the inhibitory or inductive potentials of Yuldahanso-tang (YDT) and Chungsimyonja-tang (CST), herbal formulas for Taeeumin, on cytochrome P450 (CYP450) drug metabolizing enzyme. The mechanisms for the herbal formula-drug interaction has not been well reported in spite of the chance for co-administration with conventional drugs. Methods : To evaluate the interaction potential of YDT-drug or CST-drug, the fluorescence-based enzyme assays on CYP450 isozymes including CYP3A4, CYP2C19, CYP2D6 and CYP2E1 were established in vitro. The inhibitory effects of herbal formulas were characterized with $IC_{50}$ values. Results : YDT showed inhibitory effects on CYP2D6 and CYP2E1-mediated metabolism, while it exhibited week inhibition on CYP3A4 and CYP2C19 relatively. CST exerted relatively weak inhibitory effects on the four CYP450 isozymes compared to that of YDT. Conclusions : These results suggest that the herbal formula-drug interaction could be occur when YDT are co-administered with drugs mediated by CYP2D6 or CYP2E1.

• 환경생물
• /
• 제26권2호
• /
• pp.87-93
• /
• 2008

낙동강 상류로부터 유입되는 각종 오염물질로 심하게 오염된 낙동강 하구역에서 오염정도가 다른 두 지역으로부터 문절망둑 Acanthogobius flavimanus을 채집하여 이들의 간중량지수(HSI), 생식선중량지수(GSI), 해독효소계 및 성 호르몬 수준을 비교하였다. 해독효소계로는 cytochrome P450 (CYP), NADPH-cytochrome P450 reductase (P450R), NADH-cytochrome b5 reductase (b5R), ethokyresorufin deethylase (EROD), glutathione S-transferase (GST)를 조사하였고, 성 호르몬으로는 자성호르몬인 17$\beta$-estradio(E2)을 비롯하여 웅성호르몬인 testosterone (TT), 11-ketotestolterone (11-KT)을 측정하였다. 그 결과, HSI는 site 1에서 잡은 것이 암수 모두 유의적으로 컸고, GSI는 site 1의 암컷에서 유의적으로 작았다. 그리고 성호르몬 중 11-KT과 TT농도는 오염지역에 따라 차이를 보이지 않았지만, E2농도는 site 1에서 유의적으로 높았다(p<0.05).그리고 해독효소계의 수준은 site 1의 것이 CYP와 EROD수준은 유의적으로 낮았던 반면에 P450R, b5R 및 GST 활성은 site 1에서 높았다. 이들 결과를 정리하면, 낙동강 하구에 서식하는 문절망둑은 성 호르몬 대사를 교란시키는 화합물에 의해 영향을 받고 있으며, 특히 암컷이 더욱 크게 받는다는 것을 확인할 수 있었다.