• Title/Summary/Keyword: Cytochrome P-450 3A4

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

  • 김성오
    • Journal of environmental and Sanitary engineering
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    • v.10 no.3
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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
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.05a
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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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Effects of Yuldahanso-tang and Chungsimyonja-tang on Cytochrome P450 Activities (열다한소탕과 청심연자탕의 Cytochrome P450 활성 연구)

  • Jin, Seong-Eun;Ha, Hye-Kyung;Shin, Hyeun-Kyoo
    • Journal of Sasang Constitutional Medicine
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    • v.24 no.4
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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
    • Proceedings of the PSK Conference
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    • 2003.04a
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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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Comparative liver drug metabolizing enzymes activities between Korean native cattle and swine (한우와 돼지에서 간의 약물 대사효소의 활성 비교)

  • Lee, Gwan-bok;Yun, Hyo-in;Park, Seung-chun;Kim, Min-kyu;Lee, Rae-kyung;Cho, Joon-hyung;Lee, Dong-woo
    • Korean Journal of Veterinary Research
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    • v.38 no.1
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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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Changes of Hepatic Microsomal Cytochrome P450 Monooxygenase System in Nile tilapia, Oreochromis niloticus Exposed to PCBs (PCBs노출에 의한 틸라피아, Oreochromis niloticus의 간 cytochrome P450 효소계의 변화)

  • KANG Ju-Chan;CHO Kyu-Seok
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.34 no.3
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    • pp.194-198
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    • 2001
  • The study was conducted to investigate the changes of hepatic cytochrome P450 monooxygenase system induced by dietary administration of polychlorinated biphenyls (PCBs) in the tilapia, Oreochromis niloticus. Tilapia were fed pellet with PCBs (Aroclor 1254) 0.05, 0.25 and 0.50 mg/kg body weight/day for 30 days. The dietary administration of PCBs (0.05 mg/kg) induced a significantly increased the concentration of cytochrome P450 and the activity of 7-ethoxyresorufin-O-deethylase (EROD) in the hepatopancreas at 30 days, while the augmentation of both responses was found at 20 days with a higher administration of PCBs-diet (0.25 mg/kg). However, hepatic 7-penthoxyresorufin-O-dealkylase (PROD) activity did not show any noticeable changes with the PCBs-diet 0.05-0.5 mg/kg range compared to control group during the experimental periods of 30 days in the tilapia. These results indicate that tilapia fed PCBs at the concentration of more than 0.05 mg/kg for 30 days are affected by PCBs in terms of cytochrome P450 concentration and EROD activity in the hepatopancreas.

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Drug Interaction in New Antipsychotics (새로운 항정신병약물의 약물상호작용)

  • Kim, Yong Sik;Kang, Ung Gu;Roh, Myoung Sun
    • Korean Journal of Biological Psychiatry
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    • v.7 no.1
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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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Cytochrome P450 1 gene in Eel, Anguilla japonica: cloning and expression patterns after exposure to benzo[a]pyrene (뱀장어(Anguilla japonica)에서 Cytochrome P450 1 gene 클로닝 및 benzo[a]pyrene 노출에 따른 발현 분석)

  • Jo, Hyun Ho;Kim, Ju An;Lee, Seung Hyun;Chung, Joon Ki
    • Journal of fish pathology
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    • v.33 no.2
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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.