• Title/Summary/Keyword: CYP1A2

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Vitamin E in vivo Studies on the Activity of Antioxidant Enzymes and CYP2E1 Expression in High PUFA-treated Brains (고도 불포화지방산으로 산화스트레스가 유도된 흰쥐의 뇌에서 비타민 E의 항산화효소 활성 및 CYP2E1 발현에 미치는 효과)

  • Choi, Mun-Ji;Kim, Hyun-Kyung;Lee, Myoung-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.8
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    • pp.1106-1111
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    • 2012
  • It is shown that the risk of chronic disease is increased not only by the concentration of fat in the diet but also by the composition of dietary fatty acids. We investigated the anti-oxidant effects of vitamin E on dietary polyunsaturated fatty acid-fed mice. Ninety male Sprague-Dawley rats were randomly divided into 9 groups: a normal diet group (C), 4 dietary polyunsaturated fatty acid diet groups (OA, LA, LNA, DHA), and 4 dietary polyunsaturated fatty acid diet with 0.05% vitamin E groups (OAE, LAE, LNAE, DHAE). The food efficiency in the dietary polyunsaturated fatty acid diet groups was higher than in the normal diet groups. The concentration of malondialdehyde (MDA) was significantly increased by LA and DHA fatty acids. Vitamin E significantly decreased LA and LHA-induced lipid peroxidation. The activity of superoxide dismutase and glutathione peroxidase was increased in the dietary polyunsaturated fatty acid diet groups compared to the control group, while these were decreased by supplements with vitamin E, except in the OAE group. Also, the protein expression of CYP2E1 was significantly increased in only the LNA group, while these were decreased by supplements with vitamin E. These results taken together indicate that vitamin E may have positive effects on a dietary polyunsaturated fatty acid diet-induced oxidative stress in brain tissue.

Analysis of Nitrosation Inhibition and Antioxidant Effect by Phyto-Extract Mixture (식물추출 혼합제재인 phyto-extract mixture의 니트로세이션 억제능과 항산화능 분석)

  • Kim, Ji-Hoon;Shin, Mi-Jung;Cho, Hee-Jae;Lee, Sang-Won;Jeong, Jong-Moon
    • Korean Journal of Food Science and Technology
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    • v.33 no.6
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    • pp.656-663
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    • 2001
  • The most representative nitrosamine derived from nicotine, nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK), has been reported to cause lung cancer in A/J mice. It has been also demonstrated that NNK-induced lung tumorigenesis involves $O^6-methylguanine(O^6MeG)$ formation, leading to $GC\;{\rightarrow}\;AT$ transitional mispairing during DNA replication. Our in vitro experiment, modified from the method of DBA assay, examined the ability of phyto-extract mixture to inhibit the metabolism of nicotine to nitrosamines. The production of nitromorpholine from morpholine was inhibited about 75% at the concentration of 20 mg/mL of phyto-extract mixture, which was lower than vitamine C and green tea powder. NNK, which is a pro-carcinogen in laboratory animals, is hydroxylated primarily in liver and lung by CYP 1A2, 2A6 and 3A4. A critical phase. of NNK activation is its change to an unstable metabolite methyl-diazohydroxide via CYP-mediated ${\alpha}-hydroxylation$; and then it provides a methyl group to the DNA to form DNA adducts which can easily induce mutations. $Aroclor^R$ 1254 was used to induce CYPs in the liver of a Sprague-Dawley rat. The ability of various test samples to inhibit CYPs that participate in NNK activation was evaluated, following the removal of the liver from the rat. Microsomal CYPlA2 catalyzing the conversion of NNK into strong carcinogenic chemicals was inhibited more efficiently by phyto-extract mixture than green tea powder. These results indicate that phyto-extract mixture can be used to reduce $O^6MeG$ DNA adducts for chemoprevention.

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Effect of Benzo[a]pyrene on Genes Related to the Cell Cycle and Cytochrome P450 of Saccharomyces cerevisiae

  • Lee, Hyun-Joo;Gu, Man-Bock
    • Journal of Microbiology and Biotechnology
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    • v.13 no.4
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    • pp.624-627
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    • 2003
  • Benzo[a]pyrene (B[a]P) is an environmental pollutant that has been implicated in carcinogenesis. Saccharomyces cerevisiae was treated with B[a]P, and the responses of its cytochrome P450 (CYP) enzyme and DNA-damage checkpoint genes were examined through gene expression profiles using a reverse transcription polymerase chain reaction (RT-PCR). The DNA-damage checkpoint genes tested were the chk1 and pds1 genes, involved in a metaphase arrest, the swi6 gene targeted by G1 arrest, the pol2 gene related to S phase arrest, and the cln2 gene encoding a cyclin protein, all of which are based on rad9 and rad24. Among these genes, no noticeable effect was found when the cells were exposed to various concentrations of B[a]P. However, the transcriptional activity of CYP51 was significantly different when the cells were exposed to B[a]P. Accordingly, the present results indicate that cytochrome P450 plays a more significant role than DNA-damage checkpoint genes in the response of S. cerevisiae to B[a]P.

Time-dependent Effects of Bisphenol Analogs on Ecdysteroid Pathway Related Genes in the Brackish Water Flea Diaphanosoma celebensis (Bisphenol 구조 유사체가 기수산 물벼룩 Ecdysteroid 경로에 미치는 영향)

  • In, Soyeon;Lee, Young-Mi
    • Journal of Marine Life Science
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    • v.6 no.2
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    • pp.73-79
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    • 2021
  • Bisphenol A is a representative endocrine disruptor and continuously detected in aquatic environment due to wide use, resulting in adverse effects on growth, development, and reproduction in diverse organisms as well as human. Structural analogs have been developed to substitute BPA are also suspected to have endocrine disrupting effects. In the present study, the time-dependent expression patterns of ecdysteroid synthesis (nvd, cyp314a1), receptors (EcRA, EcRB, USP, ERR), and downstream signaling pathway - related genes (HR3, E75, Vtg, VtgR) were investigated using quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) in the brackish water flea Diaphanosoma celebensis exposed to Bisphenol analogs (BPs; BPA, BPF, and BPS) for 6, 12, and 24 h. As results, the expression of nvd, cyp314a1, EcRs, USP, ERR and E75 mRNA was upregulated at 6 h exposure to BPF, which is earlier than BPA and BPS (12 h). On the other hand, HR3, E75 and VtgR mRNA levels were elevated at 6 h earlier at BPS and BPF than at BPA (12 h), but Vtg mRNA level was slightly changed within 24 h. These findings suggest that like BPA, BPF and BPS can also modulate the transcription of ecdysteroid pathway - related genes with different mechanisms, and have a potential as endocrine disruptors. This study will provide a better understanding the molecular mode of action of bisphenols on ecdysteroid pathway in the brackish water flea.

Drug Interaction Between Verapamil and Pioglitazone Long-term Administered to Rats (흰쥐에서 베라파밀과 장기투여된 피오그리타존과의 약물상호작용)

  • Choi, Dong-Hyun;Kim, Hyun-Yong;Choi, Jun-Shik
    • Korean Journal of Clinical Pharmacy
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    • v.18 no.1
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    • pp.6-10
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    • 2008
  • This study investigated the effect of long-term administration of pioglitazone on the pharmacokinetics of verapamil in rats. Pharmacokinetic parameters of verapamil were determined after oral administration of verapamil (9 mg/kg) in rats coadministered pioglitazone (0.5 mg/kg) or pretreated with pioglitazone (0.5 mg/kg) for 3 and 9 days. Compared to oral control group, the presence of pioglitazone significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) of verapamil by 48.6% (coad), 61.1% (3 days) and 56.5% (9 days), and the peak concentration($C_{max}$) by 65.1% (coad), 76.8% (3 days) and 66.4% (9 days). The absolute bioavailability (AB%) of verapamil was significantly (p<0.05) higher by 6.2% (coad), 6.7% (3 days), 6.5% (9 days) compared to control (4.2%), and presence of pioglitazone was no significant change in the terminal half-life ($t_{1/2}$) and the time to reach the peak concentration($T_{max}$) of verapamil. Our results indicate that pioglitazone significantly enhanced oral bioavailability of verapamil in rats, implying that presence of pioglitazone could be effective to inhibit the CYP3A4-mediated metabolism of verapamil in the intestine. Drug interactions should be considered in the clinical setting when verapamil is coadministrated with pioglitazone.

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Assessment of Flavin-containing Monooxygenase (FMO) Activity by Determining Urinary Ratio of Theobromine and Caffeine in a Korean Population after Drinking a Cup of Coffee

  • Chung, Woon-Gye;Kang, Ju-Hee;Roh, Hyung-Keun;Lee, Kyung-Hoon;Park, Chang-Shin;Cha, Young-Nam
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.2
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    • pp.207-213
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    • 1999
  • To examine individual variation in drug metabolism catalyzed by flavin-containing monooxygenase (FMO), 179 Korean volunteers' urinary molar concentration ratio of theobromine (TB) and caffeine (CA) was determined. Their urine was collected for 1 hr (between 4 and 5 hrs) after they drank a cup of coffee containing 115 mg CA and analyzed by an HPLC system. The lowest TB/CA ratio obtained was 0.40, the highest ratio was 15.17 (38-fold difference), and the median ratio for all subjects was 1.87. The mean was 2.66 with 2.36 S.D.. In 134 nonsmokers, the mean ratio was $2.35{\pm}1.93,$ that of 51 males was $2.30{\pm}2.26$ and 83 females was $2.37{\pm}1.85,$ respectively. There was no significant gender difference in the obtained TB/CA ratio (Mann-Whitney test; p=0.518). There were no smokers among the 83 female volunteers. In the remaining 96 male subjects, the ratio obtained in 51 nonsmokers was $2.30{\pm}2.06$ and that of 45 smokers was $3.62{\pm}3.19.$ This indicated that the TB/CA ratio was increased significantly in smokers (p=0.007). However, when the TB/CA ratios (FMO activity) obtained in all 179 Korean volunteers are compared with the urinary concentration ratios of paraxanthine (PX) plus 1,7-dimethylurate (17U) to CA (CYP1A2 activity), there was a weak but significant correlation (Pearson's correlation coefficient test; $r^2=0.28,$ p<0.0001). This indicates that, although the urinary TB/CA ratio mostly represents FMO activity, minor contribution by CYP1A2 activity cannot be ignored. In conclusion, the FMO activity measured by taking the urinary TB/CA ratio from normal healthy Korean volunteers shows marked individual variations without significant gender differences and the increased TB/CA ratio observed in cigarette smokers may have been caused by the increased CYP1A2 activity.

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In vitro and In vivo Responses of Hepatic Xenobiotic Metabolizing Enzymes in Flounder (Paralichthys olivaceus) Exposed to Formalin (Formalin에 노출시킨 넙치 (Paralichthys olivaceus) 간장 약물대사효소의 in vivo 및 in vitro 반응)

  • Lee, Ji-Seon;Ha, Jin-Hwan;Lee, Kyoung-Seon;Jeon, Joong-Kyun
    • Korean Journal of Environmental Biology
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    • v.24 no.2 s.62
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    • pp.195-200
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    • 2006
  • The response of hepatic mixed function oxygenase (MFO) system was investigated in olive flounder exposed to formalin. Hepatic microsome of olive flounder incubated in vitro with formalin demonstrated the induction of cytochrome P450 (CYP), ethoxyresorufin deethylase (EROD), cytochrome P450 reductase (P450R) and cytochrome b5 reductase (b5R) activity. In addition, olive flounder was exposed to 100, 300 and 500 ppm of formalin for 1 h and then transferred to a flow-through type of 1000 L aquarium. Hepatic MFO enzyme activity was determined for 72 h. As the result, hepatic CYP, P450R and EROD activities increased following exposure of formalin, but b5R and GST showed no significant change. These results imply that CYP and P450R can be considered as main hepatic enzymes involving in detoxification of formalin.