• Title/Summary/Keyword: Drug metabolizing enzymes

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Current Pharmacogenetics in Psychiatry (정신의학에서의 약물유전학 현황)

  • Kim, Il Bin;Lee, Yu Sang
    • Korean Journal of Biological Psychiatry
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    • v.28 no.1
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    • pp.1-6
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    • 2021
  • Pharmacogenetics is opening a new era of precision medicine in psychiatry. Drug-metabolizing enzymes are characterized by genetic polymorphisms, which render a large portion of variability in individual drug metabolism. Dose adjustment based on pharmacogenetics knowledge is a first step to translate pharmacogenetics into clinical practice. However, diverse factors including cost-effectiveness should be addressed to provide clinical recommendation. To address current challenges in pharmacogenetics testing in psychiatry, this review provides an update regarding genotyping (SNP analysis, array, and next-generation sequencing), genotype-phenotype correlations, and cost-effectiveness. The current updates on pharmacogenetics in psychiatry will provide guidance for both clinician and researchers to have a consensus in harmonizing efforts to advance the pharmacogenetics field in a part of precision medicine in psychiatry.

Nrf2 and Keap1 Regulation of Antioxidant and Phase II Enzyme Genes

  • Yamamoto, M.
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.24-42
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    • 2002
  • Antioxidant responsive element (ARE) mediates the transcriptional activation of the genes encoding phase II drug metabolizing enzymes and antioxidative stress genes. The ARE consensus sequence shows high similarity to NF-E2 binding sequence, a cisacting erythroid gene regulatory element.(omitted)

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Genetic Polymorphisms in Drug Transporters and Regulatory Xenobiotic Receptors in Korean Population

  • Lee, Sang-Seop;Shin, Jae-Gook
    • Proceedings of the Korea Environmental Mutagen Society Conference
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    • 2004.05a
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    • pp.27-29
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    • 2004
  • Drug transporters play an essential role in the absorption, distribution and elimination of clinical drugs, nutrients and toxicants. The importance of the transporters is exampled by therapeutic failure in cancer chemotherapy that is mainly caused by the overexpression of multidrug resistance (MDR)-related transporters. In addition, the transporters may involve in drug-drug interactions that lead to serious adverse drug responses and some transporters also contribute to inter-individual variation in drug responses. As an effort to understand the mechanism underlying the inter-individual variation of transporters activity, genetic and environmental factors influencing the expression or function of the transporters have extensively explored through last decade. Among them, genetic polymorphism of drug transporter encoding genes has generated much interest since the discovery of functional single nucleotide polymorphisms (SNP) of MDR1 gene. Besides drug transporters, xenobiotic receptors also modulate drug disposition by regulating the transcription of drug metabolizing enzymes and drug transporters. Among many xenobiotic receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two most well characterized since these receptors show wide substrate specificities and regulate the expression of various enzymes involved in drug disposition. Recently, several functional genetic polymorphisms were reported in PXR coding gene. In the present study, genetic polymorphisms of two drug transporters, MDR1 and BCRP, and two xenobiotic receptors, PXR and CAR, were investigated in Korean population.

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Genetic Polymorphisms in Drug Transporters and Regulatory Xenobiotic Receptors in Korean Population

  • Lee, Sang-Seop;Shin, Jae-Gook
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2004.05a
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    • pp.27-29
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    • 2004
  • Drug transporters play an essential role in the absorption, distribution and elimination of clinical drugs, nutrients and toxicants. The importance of the transporters is exampled by therapeutic failure in cancer chemotherapy that is mainly caused by the overexpression of multidrug resistance (MDR)-related transporters. In addition, the transporters may involve in drug-drug interactions that lead to serious adverse drug responses and some transporters also contribute to inter-individual variation in drug responses. As an effort to understand the mechanism underlying the inter-individual variation of transporters activity, genetic and environmental factors influencing the expression or function of the transporters have extensively explored through last decade. Among them, genetic polymorphism of drug transporter encoding genes has generated much interest since the discovery of functional single nucleotide polymorphisms (SNP) of MDRl gene. Besides drug transporters, xenobiotic receptors also modulate drug disposition by regulating the transcription of drug metabolizing enzymes and drug transporters. Among many xenobiotic receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two most well characterized since these receptors show wide substrate specificities and regulate the expression of various enzymes involved in drug disposition. Recently, several functional genetic polymorphisms were reported in PXR coding gene. In the present study, genetic polymorph isms of two drug transporters, MDR1 and BCRP, and two xenobiotic receptors, PXR and CAR, were investigated in Korean population.

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Protective Effects of Methanol Extract and Alisol B 23-acetate of Alisma orientale on Acetaminophen-Induced Hepatotoxicity in Rats

  • Yang, Ki-Ho;Choi, Seong-Hee;Park, Jong-Cheol
    • Natural Product Sciences
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    • v.18 no.2
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    • pp.121-129
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    • 2012
  • Hepatoprotective effects of methanol extract and alisol B 23-acetate of Alisma orientale were studied in acetaminophen (APAP)-treated rats. APAP increased hepatic content of lipid peroxide, which was suppressed by methanol extract and alisol B 23-acetate. The liver of rats treated with APAP had higher P-450, aminopyrine N-demethylase and aniline hydroxylase activities than those of normal control rats. The increases in hepatic drug metabolizing enzymes by the i.p. injection of APAP were significantly alleviated by the administration of methanol extract or alisol B 23-acetate. The injection of APAP also resulted in a substantial reduction of hepatic glutathione content and glutathione S-transferase activity, and the decreases were partially, but significantly, restrained by the oral administration of methanol extract prior to the i.p. injection of APAP. Hepatic activities of glutathione reductase (GR) and ${\gamma}$-glutamylcystein synthetase ${\gamma}$-GCS) were also decreased significantly in APAP-treated rats. The decreases in hepatic GR and ${\gamma}$-GCS activities by APAP injection were improved partially, but significantly, with administration of methanol extract of A. orientale. Treatment with alisol B 23-acetate also improved the hepatic ${\gamma}$-GCS activity significantly, but not GR.

Activity Changes in Phase II Drug-metabolizing Enzymes UDP-Glucoronosyl Transferase and Glutathione S-Ttansferase to Crude Oil Exposure in Mussel and Rockfish (원유의 노출이 담치와 조피볼락의 phase II 약물대사효소 UDP-glucoronosyl transferase 및 glutathione S-transferase의 활성에 미치는 영향)

  • Park Kwan-Ha;Kim Ju-Wan;Park Eum-Mi;Lim Chul-Won;Choi Min-Soon;Choe Sun-Nam;Hwang In-Young;Kim Jung-Sang
    • Environmental Analysis Health and Toxicology
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    • v.21 no.2 s.53
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    • pp.103-113
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    • 2006
  • This study examined effects of crude oil on the phase II drug-metabolizing enzymes UDP-glucuronosyl transferase (UDPGT) and glutathione S-transferase (GST) in mussel Mytilus edulis and rockfish Sebastes schlegeli, a representative bivalve and a culture fish, respectively. This work also intended indirectly to evaluate the post impact recovery from the massive oil tanker spillage accidents occurred during the summer of 1995 in the sea area off Yosu City, Chonnam. For these, enzyme activities of UDPGT and GST were examined in the fish and mussel following laboratory exposure to fresh crude oil, weathered oil, field-obtained oil residues, or in the field biota samples. Decreased GST activity was observed in rock fish following exposure to oil-soluble fraction (OSF) of fresh oil. A similar diminished GST activity was also observed after OSF of artificially weathered oil. OSF of field oil residues retrieved from the spillage area approximately 1 year later also exerted a slight inhibition of GST to rockfish. There was neither a change in UDPGT in rockfish, nor were there changes in mussel in both enzymes to any oil fractions. We could not observe any difference in the two enzymes either in rockfish or mussel sampled from the field during $1.5{\sim}2.0$ years post spillage, indicating that their enzyme systems might had been recovered by the sampling time. In conclusion, it seems that the inhibition of GST activity in rockfish is a biomarker response to crude oil exposure. The results, however, must be interpreted with care, as the inhibition nay reflect various factors such as oil concentration, duration and water temperature.

THE ALTERATION OF OXIDATIVE DAMAGE AND ACTMTIES OF METABOLIZING ENZYMES IN RATS TREATED WITH PEROXISOME PROLIFERATORS

  • Sea, Kyung-Won;Kim, Kyu-Bong;Kim, Yun-Jung;Suh, Soo-Kyung;Kim, Jong--Min;Park, Chang-Won;Kim, Jong-Won;Kim, Kwang-Jin;Choi, Ju-Young;Kim, Joo-Il;Lee, Kyung-Tae;Lee, Sun-Hee
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.116-117
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    • 2001
  • The phthalates have been shown to produce hepatic peroxisome proliferation and certain peroxisome proliferators (PPs) are also known to increase the incidence of liver tumors in rodents. In this study we investigated the correlation between oxidative injury, changes in peroxisomal and microsomal enzymes and tumor formation in PP-treated rats.(omitted)

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Effect of the Constituents of Angelicae gigantis Radix on Hepatic Drug Metabolizing Enzymes (참당귀근 성분이 간의 약물대사효소에 미치는 효과)

  • Han, Jung-Mee;Lee, Ihn-Ran;Shin, Kuk-Hyun
    • Korean Journal of Pharmacognosy
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    • v.27 no.4
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    • pp.323-327
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    • 1996
  • The ether soluble fraction of the roots of Angelicae gigantis Radix caused a significant prolongation of hexobarbital(HB) induced sleeping time in mice. Through systematic fractionation of the ether fraction monitored by bioassays, two pyranocoumarins, decursinol angelate and decursin were isolated as active principles. Decursin, as a main component, exhibited significant prolongation of HB-induced hypnosis as well as significant inhibition of hepatic microsomal drug metabolizing enzyme(DME) activities at relatively high dose which indicated that it is a weak DME inhibitor.

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