• 제목/요약/키워드: cytochrome p450 3A4

검색결과 278건 처리시간 0.024초

간세포내의 Cytochrome P450 활성에 미치는 Capsaicin의 영향 (Influences of Capsaicin on the Activities of Cytochrome P45O of Liver Cell)

  • 김성오
    • 환경위생공학
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    • 제10권3호
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    • pp.16-28
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    • 1995
  • Influences of capsaicin on the activities of cytochrome P45O of liver cell were studied in rats. Rats were provided food and water ad libitum and capsaicin and methylcellulose were gavaged for 6 days. Body weight gain and liver weight/body weight ratio, microsomal protein content and serum HDL- cholesterol content, the activity of cytochrome P450 and erythromycin demethylase, the activities of ethoxyresorufin and pentoxyresorufin O- dealkylase were determined. Capsaicin increased body weight gain but showed no significant changes on liver weight as compared with control group. Capsaicin increased the microsomal protein significantly but decreased the serum HDL- cholesterol. Capsaicin decreased the microsomal cytochrome P4SO significantly and did not show any influences on erythromycin demethylase ( cytochrome P45O III A ). Capsaicin increased the activity of pentoxyresorufin O- dealkylase ( cytochrome P45O II B) and decreased the activity of ethoxyresorufin O-dealkylase ( cytochrome P45O I A). It might be concluded that capsaicin reduced the microsomal cytochrome P45O and induced the CYP III and inhibited the CYP I A. It also might be concluded that capsaicin had no influence on CYP III A and decreased serum HDL- cholesterol. In these results capsaicin can not be used as an anti- atherosclerotic agent by increasing the CYP III A and HDL- cholesterol but it is considered that the more precise study on these theme is necessary.

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Modulation of human cytochrome P450 1B1 by 2,3',4,5'-tetramethoxystilbene(TMS) in mammary tumor cells and its application for cancer chemotherapy

  • Lee, Sang-Kwang;Kim, Sanghee;Kim, Mie-Young;Chun, Young-Jin
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2003년도 춘계학술대회 논문집
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    • pp.77-77
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    • 2003
  • We have previously shown that 2, 3' , 4, 5' -tetramethoxystilbene(TMS), a trans-stilbene analogue, is one of the most potently selective inhibitor of recombinant human cytochrome P450 1B1 in vitro. In the present studies, the effects of TMS on the expression of cytochrome P450 1B1 were investigated in human mammary cell lines such as MCF-7 and MCF-10A. (omitted)

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열다한소탕과 청심연자탕의 Cytochrome P450 활성 연구 (Effects of Yuldahanso-tang and Chungsimyonja-tang on Cytochrome P450 Activities)

  • 진성은;하혜경;신현규
    • 사상체질의학회지
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    • 제24권4호
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    • pp.84-91
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    • 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.

Modulation of Cytochrome P450 1B1 Expression by A Stilbene Analog and its Effect on the Sensitivity to Anticancer Agents in Human Cancer Cells.

  • Lee, Sang-Kwang;Park, Sung-Sik;Kim, Mie-Young;Chun, Young-Jin
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.209.1-209.1
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    • 2003
  • We have previously shown that 2, 3', 4, 5' -tetramethoxystilbene(TMS) from synthetic trans-stilbene analogues, is one of the most potently selective inhibitor of recombinant human cytochrome P450 1B1 in vitro. In the present studies. the effects of TMS on the expression of cytochrome P450 1B1 were investigated in human cancer cell lines such as MCF-7 and HL -60. TCDD-stimulated P450 1B1 protein and mRNA expression was significantly suppressed by TMS in a dose-dependent manner. (omitted)

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한우와 돼지에서 간의 약물 대사효소의 활성 비교 (Comparative liver drug metabolizing enzymes activities between Korean native cattle and swine)

  • 이관복;윤효인;박승춘;김민규;이내경;조준형;이동우
    • 대한수의학회지
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    • 제38권1호
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    • pp.17-28
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    • 1998
  • Drug-metabolizing activities of Korean native cattle and swine were investigated from viewpoints of the cytochrome P-450's level, their dependent mixed function oxidase activities, the reactive oxygen species formation and cytosolic enzyme acitivities from each liver homogenates. Level of cytochrome P-450 in the liver microsome of Korean native cattle was $0.28{\pm}0.05nmole/mg$ and that in pigs $0.35{\pm}0.03nmole/mg$. Level of cytochrome $b_5$ of Korean native cattle was $0.24{\pm}0.06nmole/mg$, and that of pigs $0.2{\pm}0.05nmole/mg$, showing no difference between two species. NADPH P-450 reductase were higher in Korean native cattle ($58.3{\pm}5.3nmole/mg/min$) than in pigs ($29.9{\pm}3.8nmole/mg/min$)(p<0.01). The activities of cytochrome P-450 dependent monooxygenases such as ethoxyresorufin O-deethylase (cattle, $96.5{\pm}12.5nmole/mg/min$ ; pigs, $13.6{\pm}2.1nmole/mg/min$), N-benzphetamine N-demethylase (cattle, $5.23{\pm}0.82nmole/mg/min$ ; pigs, $0.76{\pm}0.3nmole/mg/min$) and aniline hydroxylase (cattle, $0.95{\pm}0.1nmole/mg/min$ ; pigs, $0.33{\pm}0.08nmole/mg/min$) were much higher in Korean native cattle than in swine(p<0.01). However, the activity of testosterone $7{\alpha}$-hydroxylase was higher in swine ($90.4{\pm}1.2nmole/mg/min$) than cattle (cattle, $32.8{\pm}1.2nmole/mg/min$). Interestingly, testosterone $16{\alpha}$-hydroxylase, a marker enzyme for P-450 IIA was not detected in both animal species. These results suggest that Korean native cattle and pigs have high contents of P-450 IA1 and P-450 IIIA. Total sulfhydryl compound (cattle, $10.3{\pm}1.1nmole/mg$ ; Pigs, $14.5{\pm}1.8nmole/mg$) and glutathione related enzymes except glutathione reductase (cattle, $38.1{\pm}7.9nmole/mg/min$; swine, $22{\pm}3.6nmole/mg/min$) showed higher levels in swine than in Korean native cattle. Superoxide dismutase (cattle, $7.64{\pm}0.84nmole/mg/min$ ; pigs, $4.47{\pm}0.94nmole/mg/min$) and catalase (cattle, $30.4{\pm}3.7nmole/mg/min$ ; pigs, $17.2{\pm}1.8nmole/mg/min$) were remarkably higher in Korean native cattle than in swine (p<0.05).

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PCBs노출에 의한 틸라피아, Oreochromis niloticus의 간 cytochrome P450 효소계의 변화 (Changes of Hepatic Microsomal Cytochrome P450 Monooxygenase System in Nile tilapia, Oreochromis niloticus Exposed to PCBs)

  • 강주찬;조규석
    • 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.

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새로운 항정신병약물의 약물상호작용 (Drug Interaction in New Antipsychotics)

  • 김용식;강웅구;노명선
    • 생물정신의학
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    • 제7권1호
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    • pp.14-20
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    • 2000
  • Recently atypical antipsychotics have been used as first line agent in the treatment of schizophrenia, and also played a significant role in the treatment of many kinds of psychiatric disorders. The pharmacokinetic and pharmacodynamic properties of these newer antipsychotics are well known through preclinical and early clinical trials. However, it is important to note the limitations of the results due to its relatively short experience. Clozapine is eliminated principally by the hepatic P450 1A2 and 3A4 cytochrome enzymes. 1A2 inducers such as carbamazepine and smoking can reduce its half-life, while 1A2 inhibitors such as SSRIs, especially fluvoxamine can increase its duration of action. Carbamazepine should be avoided in a patient on clozapine because of carbamazepine's potential effects on bone marrow. Benzodiazepines tend to increase the chances of sedation, delirium and respiratory depression. Risperidone is metabolized to 9-hydroxyriperidone by the hepatic P450 2D6 cytochrome enzymes. Fluoxetine and paroxetine, 2D6 inhibitors interfere with metabolism, but 9-hydroxyrisperidone has similar biological activity as parental drug, so it has little affect on the outcome. Olanzapine shows minimal capacity to inhibit cytochrome P450 isoenzymes and shows minimal chance of drug interaction. It is eliminated principally by the hepatic P450 1A2 and 2D6 cytochrome enzymes.

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뱀장어(Anguilla japonica)에서 Cytochrome P450 1 gene 클로닝 및 benzo[a]pyrene 노출에 따른 발현 분석 (Cytochrome P450 1 gene in Eel, Anguilla japonica: cloning and expression patterns after exposure to benzo[a]pyrene)

  • 조현호;김주안;이승현;정준기
    • 한국어병학회지
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    • 제33권2호
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    • pp.153-161
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    • 2020
  • Cytochrome P450(CYP) gene is involved in the biotransformation of drugs and environmental pollutants. In this study, we analyzed the nucleotide sequence of the Anguilla japonica CYP1(AjCYP1) family gene and examined the relative expression of AjCYP1A, AjCYP1B and AjCYP1C1 in response to the exposure to environmental pollutants. After exposure to B[a]P 20mg/kg bw, the expression of AjCYP1 family gene increased over time. Among four tissues examined (liver, spleen, gill and kidney), AjCYP1 family gene was expressed significantly in the kidney. Compared with the control group, AjCYP1A was expressed about 5-fold at 48 hr, AjCYP1B about 6-fold at 24 hr, and AjCYP1C1 about 4-fold at 24 hr. However, after exposure to B[a]P 200mg/kg bw, AjCYP1A did not change in all tissues. On the other hand, AjCYP1B was expressed at about 4-fold at 24 hr in the spleen and 4-fold at 48 hr in the gill. Finally AjCYP1C1 was expressed 3.7-fold and 4.3-fold in the spleen and kidneys at 48 hr, respectively. Taken together, our results suggest that the expression of AjCYP1 gene in eel tissues might be used as a useful tool to assess the exposure to environmental pollutants in aquaculture system.