• Title/Summary/Keyword: metabolizing enzymes

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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.

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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Effects of amprolium hydrochloride on expression of drug metabolizing enzyme genes in olive flounder Paralichthys olivaceus (Amprolium hydrochloride가 넙치 Paralichthys olivaceus의 약물대사 유전자 발현에 미치는 영향)

  • Sang Hyup Park;Chang Han Kim;Jeong-wan Do;Hye-Sung Choi;Yi Kyung Kim
    • Journal of fish pathology
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    • v.36 no.2
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    • pp.337-348
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    • 2023
  • This study was undertaken to evaluate the effect of amprolium hydrochloride on detoxification process of olive flounder Paralichthys olivaceus. A series of two experiment was performed based on the LD50 value obtained for amprolium. First, thirty flounder (average weight 230.27 g; average length 27.99 cm) was randomly allocated into five groups. Treatment was carried out using intra-muscular injection of amprolium at the dose levels of 4, 8, 16, and 32 mg/kg body weight. At 8, 24 and 48 h post injection, liver and kidney were collected for expression assay of drug metabolizing enzymes and pro-inflammatory cytokine genes. We found that the interleukin-1β (IL-1β) mRNA level were induced at 32 mg/kg and CYP1A genes showed the opposite pattern, while UDP-glucuronosyl-transferase (UGT1A7) and GST were significantly reduced in the liver. Moreover, the suppression of drug metabolizing enzymes and cytokine gene in the kidney was observed after treatment. Another treatment was carried out using intramuscular injection with 4, 8, 16, and 32 mg/kg and 60, 80, 100, 120 mg/kg body weight. At 6 days post injection, liver was collected. The IL-1β expression was markedly induced in the experimental group treated with 4 mg/kg. In addition, glutathione S-transferase (GST) mRNA level was higher in the group with 4 mg/kg. In conclusion, our data suggests that amprolium seem to cause direct or indirect physical, or biological toxicity of flounders, although this drug is considered one of the safest synthetic anticoccidial drugs of the livestock industry.

Studies on Drug-metabolizing Enzymes

  • Tatsumi, Kiyoshi
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.36-41
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    • 1996
  • Drugs mean not only medicines but also poisons, pesticides, food additives, cosmetics, cleaning agents, environmental pollutants and so on, which are normally considered foreign to the body, It is important to know what happens to these drugs when they get into the body. In the past the metabolic changes of drugs had been referred to as “detoxication mechanism”, but since there are many instances in which drugs are converted in the body to more active substances. Thus, metabolism of drugs is responsible for activation and inactivation of the drugs in the body. The major reactions in drug metabolism are oxidation, reduction, hydrolysis and conjugation. Of these four areas, most of the attention had been focused on the oxidation. Therefore, in contract of ample literatures on drug-oxidizing enzymes, there were relatively few reports on drug-reducing enzymes. In recent years, however, the reduction has received an increasing interest due to its pharmacological or toxicological significance. The present lecture is organized keeping with a focus on drug-reducing enzymes which have been explored by us and by other groups.

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Effect of Ascorbic Acid on the Activities of Ethanol Metabolizing Enzymes (Ascorbic acid가 에탄올 대사효소에 미치는 영향)

  • Kim Yong-Sik
    • The Korean Journal of Pharmacology
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    • v.20 no.1 s.34
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    • pp.47-54
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    • 1984
  • Effect of ascorbic acid on various hepatic ethanol metabolizing enzymes including alcohol dehydrogenase(ADH), the microsomal . ethanol oxidizing system(MEOS), and catalase was quantitatively evaluated in liver microsomal and cytosolic preparation from Sprague-Dowley rats. In present study, ADH activities were no changed significantly by ascorbic acid. The MEOS activity, dependent on NADPH and $O_2$, was affected by azide (inhibitor of catalase) or exogenous catalase. In the presence of ascorbic acid, ethanol oxidation by rat liver microsomal preparation reacted with NADPH-generating system was increased by up to 22.5%, but decreased when liver microsome was reacted with $H_2O_2$ generated by xanthine and xanthine oxidase. Increase in the activity of the MEOS in the presence of ascorbic acid was greater in liver microsomal preparation pretreated with azide. Also ascorbic acid oxidized ethanol nonenzymatically. This ethanol oxidation induced by ascorbic acid was inhibited by OH radical scavengers (thiourea, sodium benzoate), but was not much affected by superoxide dismutase. From these results it was suggested that ascorbic acidcould interact directly with the MEOS, then promote the oxidation of ethanol. And, to some extent, ${\cdot}OH$-radicals or other radicals generated during the spontaneous autooxidation of ascorbic acid may be responsible for the production of acetaldehyde from ethanol.

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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.