• 제목/요약/키워드: Glutathione conjugates

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Naphthazarin Derivative (V) : Formation of Glutathione Conjugate and Cytotoxic Activity of 2-or 6-Substituted 5,8-Dimethoxy-1,4-napthoquinones in the Presence of Glutathione-S-transferase, in Rat Liver S-9 Fraction and Mouse Liver Perfusate

  • Zheng, Xiang-Guo;Kang, Jong-Seong;Kim, Hwan-Mook;Jin, Guang-Zhu;Ahn, Byung-Zun
    • Archives of Pharmacal Research
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    • v.23 no.1
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    • pp.22-25
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    • 2000
  • Formation of glutathione (GSH) conjugates with 2- or 6-(1-hydroxymethyl)- and 2-(1-hydroxyethyl)-DMNQ derivatives (DMNQ, 5,8-dimethoxy-1,4-naphthoquone was carried out in phosphate buffer (pH 7.4), in the presence of glutathione-S-transferase (GST), in rat liver S-9 fraction and by perfusion, and the rates of conjugates formation were compared and correlated to cytotoxicity. The GSH conjugates of 6-(1-hydroxyalkyl)-DMNQ derivatives were formed faster than 2-(1-hydroxyalkyl)-DMNQ derivatives under all of the media, implying that steric hindrance was the cause of lowering the rate of conjugate formation of 2-substituted derivatives. For both isomers, addition of GST did not improve the reaction rate, compared with that in buffer, while the reaction in the S-9 fraction and the perfusate was accelerated to a great extent. The catalytic effect of the S-9 fraction and the perfusate contain an effective system relaxing the steric hindrance of 2-(1-hydroxyalkyl)-DMNQ derivatives. Furthermore, a good correlation between the formation of the GSH conjugates and the cytotoxic activity of both naphthazarin isomers suggests that the steric hindrance is a cause of lowering the cytotoxicity of 2-isomers.

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Glutathione Conjugates of 2- or 6-Substituted 5,8-Dimethoxy-1,4-Naphthoquinone Derivatives : Formation and Structure

  • Zheng, Xiang-Guo;Kang, Jong-Seong;Kim, Yong;You, Young-Jae;Jin, Guang-Zhu;Ahn, Byung-Zun
    • Archives of Pharmacal Research
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    • v.22 no.4
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    • pp.384-390
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    • 1999
  • Thirty-four glutathione conjugates of 5,8-dimethoxy-1,4-naphthoquinones (DMNQ) were synthesized and their structure was determined. The yield of GSH conjugate was dependent on size of alkyl group; the longer the size of alkyl group was, the lower was the yield. It was also found that the length of alkyl side chain influenced the chemical shift of quinonoid protons; the quinonoid protons of 2-glutathionyl DMNQ derivatives with R=H to propyl, 6.51-6.59 ppm vs. other ones with R=butyl to heptyl, 6.64-6.68 ppm. this was explained to be due to a folding effect of longer alkyl group. Glutathione (GSH) reacted with DMNQ derivative first to form a 1,4-adduct (2- or 3-glutathionyl-1,4-dihydroxy-5,8-dimethoxynaphthalenes) and then the adduct was autooxidized to 2- or 3-glutathionyl-DMNQ derivatives. Moreover, GSH reduced DMNQ derivatives to their hydrogenated products. It was suggested that such an organic reaction might play an important role for a study of metabolism or toxicity of DMNQ derivative sin the living cells.

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Hepatotoxic Effect of 1-Bromopropane and Its Conjugation with Glutathione in Male ICR Mice

  • Lee Sang Kyu;Jo Sang Wook;Jeon Tae Won;Jun In Hye;Jin Chun Hua;Kim Ghee Hwan;Lee Dong Ju;Kim Tae-Oh;Lee Eung-Seok;Jeong Tae Cheon
    • Archives of Pharmacal Research
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    • v.28 no.10
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    • pp.1177-1182
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    • 2005
  • The hepatotoxic effects of 1-bromopropane (1-BP) and its conjugation with glutathione were investigated in male ICR mice. A single dose (1000 mg/kg, po) of 1-BP in corn oil to mice significantly increased serum activities of alanine aminotransferase and aspartate aminotransferase. Glutathione (GSH) content was dose-dependently reduced in liver homogenates 12 h after 1-BP treatment. In addition, 1-BP treatment dose-dependently increased levels of S-pro-pyl GSH conjugate at 12 h after treatment, as measured by liquid chromatography-electro-spray ionization tandem mass spectrometry. The GSH conjugate was maximally increased in liver at 6 h after 1-BP treatment (1000 mg/kg), with a parallel depletion of hepatic GSH content. Finally, 1-BP induced the production of malondialdehyde in liver. The present results suggest that 1-BP might cause hepatotoxicity, including lipid peroxidation via the depletion of GSH, due to the formation of GSH conjugates in male ICR mice.

Role of Glutathione Conjugation in 1-Bromobutane-induced Immunotoxicity in Mice

  • Lee, Sang-Kyu;Lee, Dong-Ju;Jeon, Tae-Won;Ko, Gyu-Sub;Yoo, Se-Hyun;Ha, Hyun-Woo;Kang, Mi-Jeong;Kang, Won-Ku;Kim, Sang-Kyum;Jeong, Tae-Cheon
    • Toxicological Research
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    • v.26 no.2
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    • pp.101-108
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    • 2010
  • Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.

Effect of safener fluxofenim on crop injury of chloroacetanilides and enzyme activity of glutathione S-transferase in grain sorghum seedlings (수수유묘에 있어서 fluxofenim의 약해경감효과와 glutathione S-transferase 효소활성)

  • Hwang, In-Taek;Wu, Jingrui;Hatzios, Kriton K.
    • The Korean Journal of Pesticide Science
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    • v.2 no.1
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    • pp.97-103
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    • 1998
  • Effects of safener fluxofenim was investigated for crop injury of acetanilide's upland herbicides and for enzyme activity of glutathione S-transferase (GST) in grain sorghum. Bioassay with etiolated grain sorghum [Sorghum bicolor (L.) Moench. cv. 'G522DR'] seedlings grown in agar containing metolachlor or alachlor showed that they are strong inhibitors on root growth of grain sorghum ($GI_{50}=4.5{\mu}M$ for metolachlor and $6.2{\mu}M$ for alachlor). The safener fluxofenim applied by seed soaking protected growth of grain sorghum from crop injury of metolachlor or alachlor at the concentrations of 1 to 10 ${\mu}M$. There was a significant increase in glutathione-herbicide conjugates in root tissues of fluxofenim-treated seedlings. Activities of $GST_{-metolachlor}$ and $GST_{-CDNB}$ were increased by 82% and 70%, respectively, in the cytosolic fraction of roots with fluxofenim treatment.

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Studies on the Selectivity of Herbicide Alachlor;I. Phytotoxicity and Glutathione Conjugation (제초제 Alachlor의 선택성에 관한 연구;I. 약해와 글루타치온 Conjugation 반응)

  • Park, Chang-Kyu;Hwang, Eul-Chul
    • Korean Journal of Environmental Agriculture
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    • v.6 no.1
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    • pp.44-49
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    • 1987
  • Present work has been initiated to see if inherent biochemical difference among plants is, in any way, related to the observed selectivity characteristics of preemergence herbicide, alachlor. Application of aqueous solution of alachlor onto three intact plants, soybean, chinese cabbage and barnyard grass resulted in phytotoxicity responses in the testt plants in varying degree. Examination of glutathione (and homoglutathione) contents of the test plants indicated that the phytotoxicity is inversely proportional to the peptide contents of the test plants. It was also noted that four to five water soluble metabolites are readily formed in intact seedling treated with labelled alachlor and glutathionealachlor and homoglutathionealachlor conjugates were tentatatively identified as major metabolites. It is concluded that conjugation reaction involving glutathiones and xenobiotic alachlor, a typical phase II reaction, acts as detoxification reaction in the three test plants and this would, in turn, contribute to observed selectivity of alachlor.

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Effect of Phytochelatin Synthase Expression on Degradation of Fungicide Tolclofos-methyl in Mutant Plant and Transformed yeast (돌연변이 식물 및 형질전환된 효모에서 phytochelatin synthase 발현이 살균제 tolclofos-methyl 분해에 미치는 영향)

  • Yoon, Ha-Im;Kim, Jang-Eok;Shin, Jae-Ho;Kim, Jeong-Hoe;Lee, Sang-Man
    • Korean Journal of Environmental Agriculture
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    • v.28 no.4
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    • pp.409-411
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    • 2009
  • Phytochelatins (PCs) are small-sized peptides synthesized by PC synthase (PCS) using glutathione (GSH) as a substrate, and they play an important role in the detoxification of toxic heavy metals in plants, fission yeast, and other living organisms. Recently, it has been suggested that PCS is also involved in degradation of some xenobiotics including monobromobimane. PCS cleaves the Gly residue from GSH-xenobiotics conjugates resulting in ${\gamma}$-Glu-Cys-xenobiotics, and this is to degraded further. Therefore, our research is focus on whether PCS is also involved in degradation of tolclofos-methyl, an important pesticide which has been used in ginseng cultivated areas. Heterologous expression of Arabidopsis PCS confers tolerance to tolclofos-methyl in yeast. Furthermore, PCS-deficient Cad1-3 Arabidopsis mutant showed high sensitivity to tolclofos-methyl compared with wild-type plants. These results imply that PCS is involved in degradation of tolclofos-methyl as other xenobiotics.

Identification of Glutathione Conjugates of 2, 3-Dibromopropene in Male ICR Mice

  • Lee Sang Kyu;Baik Seo Yeon;Jeon Tae Won;Jun In Hye;Kim Ghee Hwan;Jin Chun Hua;Lee Dong Ju;Kim Jun Kyou;Yum Young Na;Jeong Tae Cheon
    • Archives of Pharmacal Research
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    • v.29 no.2
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    • pp.172-177
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    • 2006
  • Hepatotoxic potential of 2, 3-dibromopropene (2, 3-DBPE) and its conjugation with glutathione (GSH) were investigated in male ICR mice. Treatment of mice with 20, 50, and 100 mg/kg of 2, 3-DBPE for 24 h caused elevation of serum alanine aminotransferase and aspartate aminotransferase activities. The hepatic content of GSH was not changed by 2, 3-DBPE. Meanwhile, the GSH content was slightly reduced when mice were treated with 2, 3-DBPE for 6 h and significantly increased 12 h after the treatment. Subsequently, a possible formation of GSH conjugate of 2, 3-DBPE was investigated in vivo. After the animals were treated orally with 20, 50, and 100 mg/kg of 2, 3-DBPE, the animals were subjected to necropsy 6, 12, and 24 h later. A conjugate of S-2-bromopropenyl GSH was identified in liver and serum treated with 100 mg/kg of 2, 3-DBPE by using liquid chromatography-electrospray ionization tandem mass spectrometry. The protonated molecular ions $[M+H]^+$ of S-2-bromopropenyl GSH were observed at m/z 425.9 and 428.1 in the positive ESI spectrum with a retention time of 6.35 and 6.39 min, respectively. In a time-course study in livers following an oral treatment of mice with 100 mg/kg of 2, 3-DBPE for 6, 12, and 24 h, the 2, 3-DBPE GSH conjugate was detected maximally 6 h after the treatment. The present results suggested that 2, 3-DBPE-induced hepatotoxicity might be related with the production of its GSH conjugate.

Effects of Ginseng Saponins on Morphine 6-Dehydrogenase

  • 김학성;정인숙;이명구;오기완
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.304-304
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    • 1994
  • The possible mechanisms of ginseng saponins on the inhibition of development of morphine tolerance and physical dependence were investigated in the aspects of morphine metabolism by morphine 6-dehydrogenase. Administration of morphine causes a reduction of non-protein sulfhydryl contents in liver, because morphinone is metabolized from morphine by morphine 6-dehydrogenase conjugates with sulfhydryl compounds. However, ginseng saponins inhibited the activity of morphine 6-dehydrogenase which catalized the production of morphinone from morphine. In addition, ginseng' saponins inhibited the reduction of non-protein sulfhydryl levels by Increasing the level of hepatic glutathione. These results suggest that the dual action of the above plays an important role in the inhibition of development of morphine tolerance and physical dependence. On the other hand, it was observed that less polar components of ginseng saponins with parent structures were more active components in vitro.

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Effects of Ginseng Saponins on Morphine 6-Dehydrogenase

  • Kim, Hack-Seang;Jeong, In-Sook
    • Korean Journal of Pharmacognosy
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    • v.25 no.2
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    • pp.160-166
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    • 1994
  • The possible mechanisms of ginseng saponins on the inhibition of the development of morphine tolerance and physical dependence were investigated in the aspects of morphine metabolism by morphine 6-dehydrogenase. The administration of morphine causes a reduction of non-protein sulfhydryl contents in the liver, because morphinone metabolized from morphine by morphine 6-dehydrogenase conjugates with sulfhydryl compounds. However, ginseng saponins inhibited the activity of morphine 6-dehydrogenase which catalyzed the production of morphinone from morphine. In addition, ginseng saponins inhibited the reduction of non-protein sulfhydryl levels by increasing the level of hepatic glutathione. These results suggest that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and physical dependence. On the other hand, it was observed that less polar components of ginseng saponins with parent structures were more active components in vitro.

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