• Title/Summary/Keyword: Epoxide hydrolase

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Effects of Holotrichia on damages of liver tissue induced by bromobenzene in rats (제조가 Bromobenzene에 의(依)한 흰쥐의 간손상(肝損傷)에 미치는 영향(影響))

  • Han, Jeong-Hoon;Shin, Hyeon-Chul;Yoon, Cheol-Ho;Kim, Jong-Dae;Jeong, Ji-Cheon;Shin, Uk-Seob
    • The Journal of Korean Medicine
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    • v.19 no.1
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    • pp.49-65
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    • 1998
  • Holotrichia was tested for the effects on damages of liver tissue induced by bromobenzene. Holotrichia was treated firstly into samples, and then bromobenzene intoxicated animal models were set with them. In vitro, the level of lipid peroxide in tissue of liver proportinally decreased with the level of concentration of extract prepared from Holotrichia It was much more decreased, when lipid peroxidation was induced with ferrous iron ($Fe&{+2}$). In vivo, after the extract was administered to the animal model for twenty days, the level of lipid peroxide in liver decreased compared to that of bromobenzene-treated group. The enzyme activities of epoxide hydrolase and glutathione S-transferase in liver highly increased in Holotrichia pre-medicating group compare with the group treated with only bromobenzene. And we can get the same results in the enzyme activities of superoxide dismutase, catalase and glutathione peroxidase. The level of glutathione followed by Holotrichia pre-medicationg administration, increased as highly as normal group in compare with the group treated with only bromobenzene. Also, the enzyme activities of AL T, AST and $\{gammer}-GTP$ in liver considerably decreased. In conclusion, Holotrichia recovers the damage of liver due to bromobenzene intoxication by the increased activities of lipid peroxidation and bromobenzene scavenging enzymes.

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Effects of the Protein Kinase A Inhibitor KT5720 on Glucagon-Mediated Decrease in Expression of Antioxidant Enzymes (Protein kinase A 억제제인 KT5720이 글루카곤 매개성 항산화 효소의 발현감소에 미치는 영향)

  • Oh Soo-Jin;Jo Jae-Hoon;Park Chang-Sik;Kim Sang-Kyum;Kim Bong-Hee
    • Environmental Analysis Health and Toxicology
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    • v.21 no.3 s.54
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    • pp.245-253
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    • 2006
  • We reported previously that glucagon decreased alpha- and pi-class glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEN) protein levels in primary cultured rat hepatocytes. The present study examines the effects of Protein kinase A (PKA) inhibitor, KT5720, on the glucagon-mediated decrease in expression of GSTs and mEN. To assess cell viability. lactate dehydrogenase release and MTT activity were examined in hepatocytes treated KT5720. Cell viability was significantly decreased in a concentration dependent manner after incubation with KT5720 at the concentrations of 1 $\mu$M or above for 24 h, which was inhibited by the cytochrome P450 inhibitor SKF-525A. In contrast, another PKA inhibitor H89 (up to 25 $\mu$M) was not toxic to hepatocytes. The glucagon-mediated decrease in expression of alpha- and pi-class GSTs and mEH was completely inhibited by 25 $\mu$M H89 and attenuated by 0.1 $\mu$M KT5720. This study demonstrates that KT5720 may cause cytotoxicity in rat hepatocytes through cytochrome P450-dependent bioactivation. The present study implicates PKA in mediating the inhibitory effect of glucagon on expression of alpha- and pi- class GSTs and mEH.

Studies on Synthetic 1,2-Benzothiazine Anti-inflammatory Agents: Pharmacological Effect and the Expression of Xenobiotic-metabolizing Enzymes (1,2-Benzothiazine계열 새로운 항염진통제에 대한 약리작용 및 대사효소발현 유형의 연구)

  • 김상건;조주연;권순경;이은방
    • YAKHAK HOEJI
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    • v.44 no.4
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    • pp.300-307
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    • 2000
  • Expression of xenobiotic-metabolizing enzymes can be altered by xenobiotics, which represents changes in the production of reactive metabolic intermediates as well as toxicities in tissues. Metabolic intermediates derived from xenobiotics are considered to produce the reactive oxygen species including drug free radicals and hydroxyl free radicals, which would be ultimately responsible for drug-induced toxicities. The effects of 1,2-benzothiazine anti-inflammatory agents on the expression of xenobiotic-metabolizing enzymes including major cytochrome P450s, microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) were studied in the liver with the aim of providing the part of information on potential production of reactive metabolites and hepatotoxicity by the agents. The synthetic compounds 24, 36 and 39 exhibited anti-inflammatory effects in rats as assessed by the Randall-Selitto method. The anti-inflammatory effect was detected as early as at 30 min after gavaging the agents with the ED5O being noted at 80 mg/kg, which was comparable to that of ibuprofen. Treatment of rats with each compound (100 mg/kg, 3d) resulted in no significant induction in the immunochemically-detectable cytochromes P45O 1A1/2, P450 2B1/2, P45O 2 Cl1 and P45O 2El. Changes in the mEN expression were also minimal, as evidenced by both Western blot and Northern blot analyses. Hepatic GST expression was slightly increased by the agents: GST Ya protein and mRNA expression was ~1.5-fold increased after treatment with compounds 24 and 39, whereas GST Yb1/2 and Yc1/2 mRNA levels were elevated 2- to 3-fold. In summary the effects of the synthetic 1,2-benzothiazines on the expression of major P45O, mEH and G57 were not significant, providing evidence that metabolic activation of the agents, potential drug interaction and hepatotoxicity would be minimal.

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Production of Chiral Phenyl Oxirane by Rhodosporidium toruloides in Hollow-fiber Reactor (Rhodosporidium toruloides를 이용한 Hollow-fiber 반응기에서의 광학활성 Phenyl Oxirane 생산)

  • 김희숙;박성훈;이은열
    • Journal of Life Science
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    • v.13 no.6
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    • pp.788-793
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    • 2003
  • Production of chiral phenyl oxirane by Rhodosporidium toruloides SJ-4 was investigated. Racemic phenyl oxirane was kinetically resolved by enantioselective hydrolysis reaction by epoxide hydrolase of R. toruloides in two-phase hollow-fiber reactor system. Dodecane with high concentration of the racemic substrate passed through the lumen side and cell suspension was recirculated through the shell side of the hollow fiber reactor For the removal of phenyl-1, 2-ethandiol to reduce the product inhibition to biocatalysts, another hollow-fiber reactor was employed to extract the diol. Racemic phenyl oxirane up to 300 mM was enantioselectively resolved with high enantiopurity (>99% ee) in hollow-fiber reactor system.

Anti-HIV and Antihepatotoxic Constituents from Medicinal Plant Resources

  • Park, Jong-Cheol;Park, Ju-Gwon;Hur, Jong-Moon;Hwang, Young-Hee;Jung, Deuk-Young
    • Plant Resources
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    • v.4 no.3
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    • pp.196-199
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    • 2001
  • Medicinal plants were screened for the inhibitory effects on human immunodeficiency virus type 1 pretense. Of the extracts tested, the strong inhibitory effects were observed in the acetone extracts of the pericarp of Camellia japonica. Camelliatannin H from the pericarp of C. japonica showed a potent inhibitory activity on HIV-1 pretense. Effects of the extract and compound from leaves of Zanthoxylum piperitum on the enzyme activities were investigated in the liver of bromobenzene-treated rats. The methanol extract and protocatechuic acid isolated from Z. pipetitum reduced the activity of aniline hydroxylase that increased by bromobenzene, while did not affect the activities of aminopyrin N-demethylase and glutathione S-transferase. The extract and protocatechuic acid recovered significantly the activity of epoxide hydrolase decreased by bromobenzene.

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THE MICROSOMAL EPOXIDE HYDROLASE(MEPHXS) POLYMORPHISMS AND THE ASSOCIATION OF MICRONUCLEI(MN) IN THE BENZENE-EXPOSED WORKERS

  • Kim, Tae-Yon;Kwon, Seul-A;Kim, Jin-Sik;Kim, Su-Young;Lee, Young-Jun;Chung, Eun-Jung;Paek, Do-Myung;Park, Jung-Keun;Chung, Hai-Won
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.134-134
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    • 2002
  • In order to investigate whether genetic polymorphisms in the mEH exon3 (Tyr139His), exon4 (His113Arg) interact with the formation of MN in benzene exposed workers, the PCR-RFLP based genotyping of 76 exposed and 115 controls were performed and cytokinesis-block micronucleus (CBMN) analysis of 56 exposed and 53 controls was employed.(omitted)

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Anti-HIV and Antihepatotoxic Constituents from Medicinal Plant Resources

  • Park, Jong-Cheol;Park, Ju-Gwon;Hur, Jong-Moon;Hwang, Young-Hee;Jung, Deuk-Young
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2001.11a
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    • pp.68-73
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    • 2001
  • Medicinal plants were screened for the inhibitory effects on human immunodeficiency virus type 1 pretense Of the extracts tested, the strong inhibitory effects were observed in the acetone extracts of the pericarp of Camellia japonica. Camelliatannin H from the pericarp of C. japonica showed a potent inhibitory activity on HIV- 1 pretense. Effects of the extract and compound from leaves of Zanthoxylum piperitum on the enzyme activities were investigated in the liver of bromobenzene-treated rats. The methanol extract and protocatechuic acid isolated from Z. piperitum reduced the activity of aniline hydroxylase that increased by bromobenzene, while did not affect the activities of aminopyrin N-demethylase and glutathione S-transferase The extract and protocatechuic acid recovered significantly the activity of epoxide hydrolase decreased by bromobenzene.

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Anti-lipid Peroxidative Principles from the Stem Bark of Kalopanax pictus Nakai

  • Choi, Jong-won;Han, Youn-Nam;Lee, Kyung-Tae;Park, Kun-Yong;Kwak, Tae-Soon;Kwon, Sang-Hyuk;Park, Hee-Juhn
    • Archives of Pharmacal Research
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    • v.24 no.6
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    • pp.536-540
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    • 2001
  • Hepatic lipid peroxide contents were examined in bromobenzene-treated rats firstly after the oral administration of MeOH extract of Kalopanax pictus stem bark its n-BuOH fraction, EtOAc fraction and an alkaline hydrolysate of the n-BuOH fraction, and secondly after the intraperitoneal administration of hederagenin monodesmosides and bisdesmosides. Two hederagenin monodesmosides, kalopanaxsaponin A (KPS-A) and sapindoside C, exhibited significant anti-lipid peroxidation effects after intraperitoneal administration at doses of $10-30{\;}{\mu}mole/kg$, whereas their bisdesmosides did not exhibit any significant activity. These results suggest that it is the hederagenin monodesmosides that are responsible for anti-lipid peroxidation in vivo. The activity of KPS-A was established by the observation of decreased aminopyrine N-demethylase activity and increased epoxide hydrolase activity.

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