• Proceedings of the Korean Biophysical Society Conference
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• 2002.06b
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• pp.53-53
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• 2002

Inhibitory effects of Cu$\^$2＋/ on the cytochrome P450 (P450)-catalyzed reactions of liver microsomes and reconstituted systems containing purified P450 and NADPH-P450 reductase (NPR) were seen. However, Zn$\^$2＋/, Mg$\^$2＋/, Mn$\^$2＋/, Ca$\^$2＋/, and Co$\^$2＋/ had no apparent effects on the activities of microsomal P450s. Cu$\^$2＋/ inhibited the reactions catalyzed by purified P450s lA2 and 3A4 with IC$\sub$50/ values of 5.7 and 8.4 ${\mu}$M, respectively.(omitted)

• Journal of Nutrition and Health
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• v.35 no.6
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• pp.643-649
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• 2002

This study was done to investigate effects of ${\gamma}$-irradiated pork feeding on the formation of glutathione S-transferase placental form positive (GST-P$^{+}$) foci, lipid peroxidation, cytochrome P450 system and microsomal glucose 6-phosphatase activity in diethylnitrosamine (DEN)-initiated rat hepatocarcinogenesis. Weaning Sprague-Dawley male rats were fed the diet containing ${\gamma}$-irradiated ground pork at the dose of 0, 3, 10, 30 kGy as a 20％ of protein source for 8 weeks. One week after feeding, rats were intraperitoneally injected twice with a dose of DEN (50 mg/kg BW). As a promote.,0.05％phenobarbital was fed in drinking water from one week after DEN treatment until the end of experiment. At the end of 8th week, rats were sacrificed and hepatic GST-P$^{+}$ foci, microsomal malondialdehyde (MDA) and conjugated diene contents were determined. In addition, cytochrome P450 content and the activities of NADPH cytochrome P450 reductase and glucose 6-phosphatase were also measured. There was no significant effect by gamma irradiation on microsomal MDA content, conjugated diene, cytochrome P450 content and activities of NADPH cytochrome P450 reductase and glucose 6-phosphatase. However with DEN treatment, microsomal MDA content showed a increasing tendency. Cytochrome P450 content was also significantly increased while microsomal glucose 6-phophatase activity was significantly decreased with DEN treatment. However the activity of NADPH cytochrome P450 reductase was not affected. An interesting finding in this study was that the number and area of hepatic GST-P$^{+}$ foci of rats fed gamma irradiated pork were tended to be decreased by high dose of irradiation, but were not significantly different. These results might imply that the consumption of low dose of gamma irradiated pork does not affect the formation of hepatic GST-P$^{+}$ foci and lipid peroxide and membrane stability.ability.

• Journal of Society of Preventive Korean Medicine
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• v.15 no.1
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• pp.1-16
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• 2011

Objectives : The mechanisms for korean traditional medicine-drug interaction has not been well reviewed in spite that the chance for co-administration with western drugs or diet supplements has been increased. Especially, it is well known that various cytochrome P450s play a major role in drug-drug interaction. Of course, Korean traditional medicines is not excluded in a view of metabolism or biotransformation by cytochrome P450. This article was focused on reviewing the possible roles of cytochrome P450 in Korean traditional medicine-drug interaction, Also, the directions for further studies were suggested in terms of Korean traditional medicine-drug interaction. Methods : New studies for korean traditional medicine-drug interaction were reviewed and summarized in terms of cytochrome P450 activities by various Korean traditional medicines and western drugs. Results and Conclusions : Even if a few studies related to Korean traditional medicine-drug interactions was carried out, almost no studies for Korean traditional medicine-drug interactions has been found in a view of cytochrome P450. It was suggested that Korean traditional medicines and their decoction should be analyzed that how they effects on cytochrome P450, expecially CYP 1, 2, 3 families and how they interact with western drugs.

• The Korean Journal of Pesticide Science
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• v.7 no.1
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• pp.45-50
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• 2003

This study was conducted to understand the role of oxidative enzyme cytochrome $P_{450}$ in the bioactivation of benfuracarb and to know metabolites of benfuracarb by cytochrome $P_{450}$. The bimolecular imhibition rate constant $(k_i)$ of benfuracarb on acetylcholinesterase (AChE) was as low as $1.1{\times}10^3\;M^{-1}\;min^{-1}$, suggesting that benfuracarb should be activated for its toxic action. The potency of benfuracarb on AChE in the oxidase system (cytochrome $P_{450}$ + NADPH) in vitro was 10-fold higher than that of control (cytochrome $P_{450}$). Such a similar result was also found in the oxidase + PBO system. In vivo the $I_{50}$ of benfuracarb was 22.7mg $kg^{-1}$, but pie-treatment of piperonyl butoxide (PBO) reduced the $I_{50}$ by >100mg $kg^{-1}$. This result suggests that cytochrome $P_{450}$ was involved in the activation of benfuracarb. Using microsomal oxidase system, metabolites of benfuracarb were elucidated. Fifty-eight percent of benfuracarb was converted to carbofuran, a major toxic metabolite, in the oxidase system, while only less than two percent of benfuracarb was converted to carbofuran in the oxidase + PBO system. These results also suggest that cytochrome $P_{450}$ was involved in the activation of benfuracarb. Overall results indicate that cytochrome $P_{450}$ could be involved in the bioactivation of benfuracarb to carbofuran.

• Korean journal of applied entomology
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• v.32 no.3
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• pp.291-299
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• 1993

Midgut tissues from 4 insect specIes were exammed for the activity of cytochrome P-450 monooxygenases, a major enzyme involved in chemical detoxification. When Helicoverpa assulta larvae were reared on an artificial d;et, the specific activity of the midgut cytochrome P-450 monooxygenases (MFO) was :3 times higher than that of the fat body, The specific activity of the midgut cytochrome P-450 monooxygenases was higher in H. assul/a larvae when reared on Nicotiana tabacum leaves than when on CapsIcum annuum fruits or an artificial diet. In the case of Hyphantria cunea larvae, Tilia megaphyllo leaves were the best in inducing midgut cytochrome P-450 monooxygenases activity. When larvae of H. assulta, Spodoptera exigua, H. cunea and Spodoptera litura were reared on their own artificial diet, the highest activity was seen in S. exigua larvae which is a polyphagous and insecticide-resistant strain.

• Archives of Pharmacal Research
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• v.21 no.3
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• pp.305-309
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• 1998

Human cytochrome P450 1A2 is one of the major cytochrome P450s in human liver. It is known to be capable of activating a number of carcinogens such as arylamines and heterocyclic amines. In order to develop the new bacterial mutagenicity test system with human P450, a full length of human P450 1A2 cDNA inserted into pCW bacterial expression vector was introduced to Escherichia coli WP2 uvrA strain which is a well-known E. coli strain for bacterial reverse mutagenicity assay. Expressed human P450 1A2 showed typical P450 hemoprotein spectra. Maximum expression was achieved at 48 hrs after incubating at $30^{\circ}C$ in terrific broth containing ampicillin, IPTG and other supplements. High level expression of P450 1A2 in E. coli WP2 uvrA membranes was determined in SDS-PAGE. The well-known mutagens 2-aminoanthracene and MElQ increased the revertant colonies of E. coli WP2 uvrA expressing human P450 1A2 without an exogenous rat hepatic post-mitochondrial supernatant (S9 fraction) in a dose-dependent manner. The results show that the functional expression of human P450 in bacterial mutagenicity tester strain will provide a useful tool for studying the mechanism of the mutagenesis and carcinogenesis of new drugs and environmental chemicals.

• Journal of the Korean Applied Science and Technology
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• v.29 no.3
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• pp.435-442
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• 2012

The cytochrome P-450 enzymes (CYP 2A6) regulate many endogenous signaling molecules and drugs. Aryl alkynes such as 2-ethynylnaphthalene are important P450 inhibitors which have been extensively studied as medicines or as an effective chemical probes for profiling mouse liver microsomal P-450. Here we have synthesized indole-based novel P450 inhibitor, 5-ethynyl indole 3, and showed that it has successfully inhibited CYP 2A6 by chemical inhibition reaction. By using HPLC equipped with a photo diode array(PDA) detector, all of the peaks derived from the enzymatic reaction have been characterized.

• Toxicological Research
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• v.23 no.3
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• pp.189-196
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• 2007

Cytochrome P450 (P450) enzymes are the major catalysts involved in the biotransformation of various drugs, pollutants, carcinogens, and many endogenous compounds. Most of chemical carcinogens are not active by themselves but they require metabolic activation. P450 isozymes playa pivotal role in the metabolic activation. The activation of arylamines and heterocyclic arylamines (HAAs) involves critical N-hydroxylation, usually by P450. CYP1A2 plays an important role in these reactions. Broad exposure to many of these compounds might cause carcinogenicity in animals and humans. On the other hand, P450s can be also involved in the bioactivation of other chemicals including alcohols, aflatoxin B1, acetaminophen, and trichloroethylene, both in humans and in experimental animals. Understanding the P450 metabolic activation of many chemicals is necessary to develop rational strategies for prevention of their toxicities in human health. An important part is the issues of extrapolation between species in predicting risks and variation of P450 enzyme activities in humans.

• Korean Journal of Veterinary Research
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• v.44 no.2
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• pp.185-193
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• 2004

The effects of membrane lipid peroxidation and retinyl palmitate on rat liver microsomal functions were investigated in vitro. Rat liver homogenates exposed to oxygen tension for 0, 3, 6, 9 or12 hours and lipid peroxidation levels were evaluated by the measurements of fluorescence intensity, malondialdehyde (MDA) and retinyl palmitate. The fluorescence intensity of homogenates and microsomes were elevated and retinyl palmitate concentrations were decreased. But the concentration of MDA was not affected to exposure time. Therefore, fluorescence intensity and retinyl palmitate concentration were used to analyze the correlation between lipid peroxidation and microsomal functions. To investigate the liver microsomal functions, the microsome was isolated from rat liver homogenates exposed to oxygen. The concentration of cytochrome P450 and the activity of NADPH-cytochrome P450 reductase in liver microsomes were gradually decreased with increasing the exposure time. The correlation between fluorescence intensity of microsomes showed a very high inverse correlation of -0.97 and -0.93, respectively. The decrease of cytochrome P450 concentration was due to the regeneration of cytochrome P450 to cytochrome P420. Also, the activities of cytochrome P450-dependent aminopyrine demethylase and benzpyrene hydroxylase of liver microsomes were gradually decreased with increasing the exposure time. The correlation with fluorescence intensity of microsome showed a high inverse correlation of -0.97 and -0.91, respectively. The retinyl palmitate concentrations of rat liver homogenates were decreased with increasing the exposure time. The decrease of retinyl palmitate concentration was followed by a low concentration of cytochrome P450 and activity of NADPH-cytochrome P450 reductase. The correlation indicated high direct correlation of 0.92 and 0.93, respectively. The decrease of retinyl palmitate concentration was also accompanied by the reduction of aminopyrine demethylase and benzpyrene hydroxylase activities. The correlation was analyzed a high direct correlation of 0.90 and 0.85, respectively. In conclusion, these studies have shown that the membrane lipid peroxidation of rat liver microsome proportionally decreased microsomal enzyme activities in vitro experiments.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.6
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• pp.859-866
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• 1995

This study was done to investigate the effects of chronic ethanol feeding on hepatic microsomal cytochrome system, lipid peroxidation and peroxide metabolizing enzyme activities in 2-acetylaminofluorene(2-AAF) treated rats. Male Sprague-Dawley rats, weighing 120~125g, were pair-fed liquid diets containing 35% of total calories either as ethanol or isocaloric carbohydrates for 6 weeks. After 4 weeks of experimental diet feeding, 2-AAF(100mg/kg body weight) was injected twice a week intraperitoneally. Both weight and percent liver weight per body weight were significantly changed by ethanol feeding. Hepatic microsomal lipid peroxide value and the activities of glutathione(GSH) peroxidase and GSH reductase were not changed by either ethanol or 2-AAF treatment. However the analysis of cytochrome systems showed that both ethanol and 2-AAF increased cytochrome P-450 and bs contents although cytochrome P-450 content was moe affected by 2-AAF while cytochrome b5 content by ethanol. Cytosolic GSH S-transferase activity, which is often elevated during chemical carcinogenesis, also significantly increased by either ethanol feeding or 2-AAF treatment. Overall values for the cytochrome contents and GSH S-transferase activities were highest in 2-AAF treated rats fed ethanol. These results might support the hypothesis that the increase in liver cancer risk associated with chronic ethanol consumption might be due to, at least in part, enhancement of carcinogen bioactivation by ethanol.