• Journal of Nutrition and Health
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• 제29권7호
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• pp.689-702
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• 1996

The purpose of this experiment was to compare the effects of tryptophan administration on nutritional status of female rats which consumed reserpine and 6% casein diet with different carbohydrate contents(87%, 65%, 44% respective). Final body weight, body weight gain, FER, plasma amino acid concentration and microsomal cytochrome P 450 content in liver were measured and microscopic structure of hepatocytes was observed. In low-protein diet, the higher the carbohydrate content of diet was, the lower the damage was in the rat's liver. Tryptophan administration after dose of reserpine induced more effective recovery from liver damage of rats in high carbohydrate diet group than that in low carbohydrate diet group. In conclusion, the general nutritional assessments such as final body weight and body weight gain provided better estimate of the degree of structural changes in hepatocytes than functional assessment such as plasma amino acid concentration or liver microsomal cytochrome P450.

• Toxicological Research
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• 제23권3호
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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.

• Toxicological Research
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• 제14권3호
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• pp.293-300
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• 1998

Previous studies have shown that the heterocycles including thiazoles are efficacious in inducing phase phase II metabolizing enzyme as well as certain cytochrome P450s and that the inductin of these matabolizing enzymes by the heterocyclic agents is highly associated with their hepatotoxicity. In the present study, the effects of benzylisothiazole (BIT), which has a isothiazole moiety, on the expression of microsomal epoxide hydrolase (mEH), major glutathione S-transerases and cytochrome P450s were studied in the rat liver in association with its hepatotoxicity. Treatment of rats with BIT(1.17 mmol/kg, 1~3d) resulted in substantial increases in the mEH. rGSTA2, rGSTA2, rGSTM1 and rGSTM2 mRNA levels, whereas rGSTA3 and rGSTA5 mRNA levels were increased to much lesser extents. A time-course study showed that the mRNA levels of mEH and rGSTs were greater at 24hr after treatment than those after 3 days of consecutive treatment. Relative changes in mEH and rGST mRNA levels were consistent with those in the proteins, as assessed by Western immunoblot analysis. Hepatic cytochrom P450 levels were monitored after BIT treatment under the assumption that metabolic activation of BIT may affect expression of the enzymes in conjunction with hepatotoxicity. Immunoblot analysis revealed that cytochrome P450 2B1/2 were 3-to 4-fold induced in rats teatd with BIT(1.17 mmol/kg/day.3days), whereas P450 1A2, 2C11 and 3A1/2 levels were decreased to 20~30% of those in unteatd rats. P450 2E1 was only slightly decreased by BIT. Thus, the levels of several cytochrome P450s were suppressed by BIT treatment. Rats treated with BIT at the dose of 1.17mmol/kg for 3 days exhibited extensive multifocal nodular necrosis with moderate to extensive diffuse liver cell degeneration. No notable toxicity was observed in the kidney. These results showed that BIT induces mEH and rGSTs in the liver with increases in the mRNA levels, whereas the agent significantly decreased major cytochrome P450s. The changes in the detoxifying enzymes might be associated with the necrotic liver after consecutive treatment.

• 한국약용작물학회지
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• 제15권6호
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• pp.437-443
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• 2007

홍삼의 물추출물을 장기간 흰쥐에 급여했을 때 흰쥐 간의 이물질대사효소 활성도 유도에 미치는 영향을 조사하였다. 홍삼 물추출물의 급여농도는 25 mg/kg body weight이었으며, 간의 이물질대사효소 유도제는 항경련제 PB (80 mg/kg)와 발암제 3-MC (20 mg/kg)을 사용하였다. 간에서 이물질대사에 관여하는 cytochrome P-450의 함량, cytochrome P-450 dependent monooxygenase인 ECOD와 BPDM, cytochrome P-450 reductase와 GST의 활성도는 PB와 3-MC 투여에 의해서 대조군과 홍삼투여군 모두 크게 증가되었다. 흰쥐의 나이가 3개월에서는 두 유도제를 투여했을 때 이물질대사효소의 활성은 대조군이 인삼투여군에 비해 상대적으로 더 많이 유도되었다. 그러나 12개월에서는 두 시험군 모두 유도정도가 감소하였으나 홍삼투여군은 그 활성도 감소정도가 대조군에 비해 상대적으로 크지 않았다. 한편 두 그룹 모두 이물질대사 효소 중 cytochrome $B_5$ 함량과 cytochrome $b_5$ reductase의 활성도는 PB와 3-MC 투여에 의해서 뚜렷한 차이를 보이지 않았다. 따라서 이러한 결과는 흰쥐에 홍삼의 장기간 급여는 간에서 효소유도제의 이물질대사효소유도 정도를 조절하여 무독화에 기여할 수 있다는 것을 의미한다.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.3-5
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• 2003

여성호르몬으로 잘 알려진 estrogen은 난소의 granulosa 세포와 정소의 Sertoli 세포에서 주로 생성되는 것으로 알려져 있으며 최근엔 사람의 지방, 근육, 뇌, 뼈세포 등에서의 합성 가능성과 각 조직에서 생성되는 estrogen 의 생리학적인 기능에 관해 많은 관심이 모여져 왔다. 다른 steroid처럼 지방친화적인 (lipophilic) estrogen은 세포막과 핵막을 쉽게 통과하여 목표세포 (target cell)의 핵에 존재하는 estrogen receptor (ER)에 결합하여 특정 유전자를 발현에 관여하는 것으로 알려져 있다. Cytochrome P450 Aromatase (간략히, aromatase)는 steroid hormone을 합성하는 마지막 단계에서 androgens을 estrogens으로 전환시키는데 관여하는 효소이다. Aromatase의 substrate (기질)로 사용되는 androgen에는 androstenedione과 testosterone 등이 있으며, 최종 산물로써 estrone(E1)이나 17$\beta$-estradiol(E2) 등의 estrogen이 생성된다. Aromatase는 steroidogenic tissues의 세포내 골지체에 존재하는 것으로 알려져 있으며, NADPH-cytochrome P450 reductase와 함께 복합체로써 존재한다. NADPH-cytochrome P450 reductase는 다른 steroid hormone에 관여하는 효소들과도 복합체를 형성하여 다른 steroid hormone을 합성할 수 있으므로, 어떤 조직에서 여성호르몬이 만들어질 수 있느냐 하는 것은 그 조직에서 aromatase 단백질이 만들어지느냐에 따라서 결정된다.

• The Plant Pathology Journal
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• 제39권6호
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• pp.566-574
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• 2023

The aim of this study was to investigate the regulation of lantipeptide production in Streptomyces globisporus SP6C4, which produces the novel antifungal lantipeptides conprimycin and grisin, and to identify the role of cytochrome P450 (P450) in tis regulation. To investigate the regulation of lantipeptide production, we created gene deletion mutants, including ΔP450, ΔtsrD, ΔlanM, ΔP450ΔtsrD, and ΔP450ΔlanM. These mutants were characterized in terms of their morphology, sporulation, attachment, and antifungal activity against Fusarium oxysporum. The gene deletion mutants showed distinct characteristics compared to the wild-type strain. Among them, the ΔP450ΔlanM double mutant exhibited a recovery of antifungal activity against F. oxysporum, indicating that P450 plays a significant role in regulating lantipeptide production in S. globisporus SP6C4. Our findings highlight the significant role of P450 in the regulation of lantipeptide production and morphological processes in S. globisporus. The results suggest a potential link between P450-mediated metabolic pathways and the regulation of growth and secondary metabolism in SP6C4, thereby highlighting P450 as a putative target for the development of new antifungal agents.

• 한국수산과학회지
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• 제34권3호
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• pp.194-198
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• 2001

PCBs의 경구 투여에 의한 틸라피아, Oreochromis niloticus의 간 cytochrome P450 효소계의 변화를 30일간 관찰하였다. 30일 동안 PCBs 0.05, 0.25 및 0.50mg/kg을 투여했을 때, HSI는 각각 1.81, 1.72 및 $1.54\%$ 감소하였으나, 유의한 차이는 인정되지 않았다. PCBs 0.05mg/kg에 노출된 간 cytochrome P450 농도는 30일째 대조구에 비해 1.4배 유의한 증가를 나타냈고, 0.25mg/kg 이상에서는 실험 20일 이후부터 유의적으로 증가하였다. EROD 활성도는 PCBs 0.05 mg/kg에서 실험 30일째부터 유의하게 증가하여 약 8배 높게 나타났다. 또한, PCBs 0.25mg/kg이상에서는 실험 20일째부터 유의하게 증가하여 30일째부터는 각각 18 및 22배의 증가를 나타냈다. PROD는 PCBs $0.05\~0.50mg/kg$에 노출시킨 개체에서 $0.78\~1.93$pmole/mg protein이 측정되어 대조구에 비해 뚜렷한 변화는 관찰되지 않았다. 이상의 결과는 자연 수역에서 PCBs의 잔류에 따라 먹이를 통해 틸라피아의 체내에 적어도 0.05 mg/kg 이상이 30일간 이상 계속적으로 유입될 경우에 간 cytochrome P450농도 및 EROD 활성도는 증가될 것으로 추정된다.

• 한국수의병리학회지
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• 제1권1호
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• pp.33-39
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• 1997

We investigated metabolism and carcinogenesis in livers of Sprague-Dawley rats fed juices and pelleted diets containing Korean native plants petasites japonicus Maxim by evaluating cell localization and expression of cytochrome P450s and GST-P. Anti-cytochrome P450s application in liver sections revealed three to four times increased expression of cytochrome P450E1 immunoreactivity in degenerative hepatocytes when compared to histologically normal hepatocytes. Anti-GST-P in showed positive pren plastic foci as well as in individual hepatocytes randomly scattered throughout all liver sections examined. Additionally GST-P was evident in proliferative endothelial cells and biliary epithelial cells in exposed rat livers. These results suggested that the increased level of cytochrome P4502E1 in affected hepatocytes was a direct consequence of Petasites japonicus toxicity. Further immunoreactivity to anti-GST-P in hepatocytes endothelial cells and biliary epithelial cells indicated a possible preneoplastic effects of Petasites japonicus in Sprague-Dawley rat.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.1-18
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• 2022

Drug-drug interactions are a major cause of hospitalization and deaths related to drug use. A large fraction of these is due to inhibition of enzymes involved in drug metabolism and transport, particularly cytochrome P450 (P450) enzymes. Understanding basic mechanisms of enzyme inhibition is important, particularly in terms of reversibility and the use of the appropriate parameters. In addition to drug-drug interactions, issues have involved interactions of drugs with foods and natural products related to P450 enzymes. Predicting drug-drug interactions is a major effort in drug development in the pharmaceutical industry and regulatory agencies. With appropriate in vitro experiments, it is possible to stratify clinical drug-drug interaction studies. A better understanding of drug interactions and training of physicians and pharmacists has developed. Finally, some P450s have been the targets of drugs in some cancers and other disease states.

• Toxicological Research
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• 제11권2호
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• pp.215-221
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• 1995

This paper examines the effects of dietary polyunsaturated fatty acid/saturated fatty acid (p/s) ratios and butylated hydroxytoluene (BHT) on the hepatic microsomaI mixed-function oxidase sy. stem in 2~acetylaminofiuorene (2-AAF) treated rats. Sprague-Dawley male rats were fed the diet of beef tallow (p/s 0.08), beef tallow plus soybean oil (p/s 1.0), and soybean oil (p/s 4.0) at the level of 15%fat and with or without 0.3% BHT. After 2-AAF was injected twice at the ages of 23 and 27 weeks, cholesterol/phospholipid molar ratio, thiobarbituric acid reactive substances (TBARS) level, cytochrome P450, cytochrome $b_5$, NADPH-cytochrome $b_5$, and NADPH-cytochrome c reductase activity were measured from isolated hepatic microsomal fractions. In the beef tallow (p/s 0.08) and beef tallow plus soybean oil (p/s 1.0) groups, cholesterol/phospholipid molar ratio showed decreasing tendency by 2-AAF and BHT. Cytochrome P-450 content was decreased in the group of soybean oil (p/s 4.0) and NADPH-cytochrome c reductase activity was increased by 2-AAF and BHT in all the dietary groups. While TBARS levels were increased by 2-AAF in all the dietary groups, they were reduced by BHT in the soybean oil (p/s 4.0) group. These results suggest that long term intake of soybean oil (p/s 4.0) diet induced changes in the nature of microsomal membrane and induced less cytochrome P-450, low level feeding of BHT increased cytochrome c reductase activity and lowered microsomal lipid peroxidation levels, which were increased by 2-AAF treatment.