• Title/Summary/Keyword: glutathione-s-transferase (GST)

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Molecular Basis of Organospecific Carcinogensis by Chemical Carcinogens-Study with Breast Cancer Specific Carcinogens: DMBA as an Indirect-Acting carcinogen and NMU as a Direct-Acting cancinogen. (화학적 발암원의 조직 특이성 암유발기전 - DMBA와 NMU의 선택적 유암 발생기전을 중심으로 )

  • 박종영;김승원;박상철
    • Environmental Mutagens and Carcinogens
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    • v.9 no.1
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    • pp.1-12
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    • 1989
  • To study the selective organospecific carcinogenesis by the specific chemical carcinogens, the breast cancer induction model by oral administration of 7, 12-dimethylbenzanthracene (DMBA) or by intravenous injection of N-methylni-trosourea (NMU) on female rats was analyzed. In the present experiment, we compared the effexts of ages on the chemical mammary carcinogenesis by studying the metabolic system of the carcinogenic activation, detoxification or DNA damage and repair. The breast tumor incidence was significantly higher in the young rats of 50 days old than in those of one year old rats. As an index of organospecific DNA damage or repair, the in vivo covalent binding index(CBI) of the specific organs by the specific chemical carcinogens was monitored. And for the analysis of carcinogenic activation, the quantity of cytochrome P450`s was determined with the respective type-specific monoclonal antibody, while the detoxication capacity was deduced by the activity monitoring of glutathione S-transferase (GST) and peroxidase. The skin tissues of the mammary region had the highest CBI with both of DMBA and NMU at 50 days of age. And there were contrasting differences in the contents of carcinogenic activation and detoxication system: that is, the content of T.C.D.D.-inducible cytochrome P450 was high, while the activities of GST and peroxidase was low in the mammary skin tissues at tumor prevalent age. These results led us to conclude that the molecular organospecific carcinogenesis, as illustrated with mammary carcinoge-nesis by DMBA and NMU, is operated probably through the differential capacity of the target tissues in the high carcinogenic activation, low detoxication and the low DNA repair function.

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Effect of Dietary Selenium Levels on Antioxidative Defense System and Oxidative Damage of Liver Tissue in Lead Administered Rats (식이 Selenium 함량이 납중독 흰쥐 간조직의 항산화계와 세포 손상에 미치는 영향)

  • 임정교;이순재
    • Journal of the East Asian Society of Dietary Life
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    • v.11 no.4
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    • pp.259-267
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    • 2001
  • This study was to investigate the effect of selenium on hepatic antioxidative defense system and oxidative damage in lead-administered rats. Male Sprague-Dawley rats weighing 140$\pm$5g were divided into one normal group(Se, 0 ppm) and three lead groups according to dietary levels of selenium supplementation: Pb0(Se, 0 ppm), PbS(Se, 0.5 ppm), and PbSS(Se, 1.0 ppm). All experimental groups were fed the experimental diet ad libitum for 4 weeks, and lead groups fed one containing 2,000 ppm lead acetate. Liver superoxide dismutase(SOD) activities in Pb0 group increased compared with other experimental groups. Liver gluthathione peroxidase(GSH-px) activities in Pb0 group decreased compared with normal group, but those of PbS and PbSS groups significantly increased compared with Pb0 group. Glutathione S-transferase(GST) activities decreased in Pb0 group and not significantly different from PbS and PbSS groups compared with normal group. Reduced glutathione(GSH) contents and GSH/GSSG of liver in Pb0 group were lower than those of other groups. Liver vitamin E contents in Pb0 group were about 50% of the normal group, but those of PbSS and PbS increased more than Pb0 group. Liver damage in electron microphotography process decreased in RER, showed an increase in Iysosome and also an increase in swelling of mitochondria. and ordered as follows : PbSS. PbS. and Pb0. It was concluded that high levels of dietary selenium had protective effects on peroxidative damage of hepatic cell accompanied with increased antioxidative defense system in lead-administered rats.

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Effect of N-3, N-6 Fatty Acid and d-Limonene Treatment on Membrane Lipid Composition and Protein Kinase C Activity in Experimental Rat Hepatocarcinogenesis (쥐의 간 발암과정에서 N-3, N-6 지방산 섭취 및 d-Limonene 투여가 생체막 지질조성 및 Protein Kinase C 활성도에 미치는 영향)

  • 김미정;김정희
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.8
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    • pp.1328-1336
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    • 2003
  • This study was done to investigate the effects of n-3, n-6 fatty acid and d-limonene on the hepatic membrane lipid composition, protein kinase C (PKC) and glutathione S-transferase (GST) activities in experimental rat hepatocarcinogenesis. Sprague-Dawley female rats were fed with two different types of dietary oil for 20 weeks. Corn oil (CO) and sardine oil (SO) were used at 15% by weight as a source of n-6 and n-3 fatty acid, respectively. One week after feeding, rats were intraperitoneally injected twice with a dose of diethylnitrosamine (DEN, 50 mg/kg body weight) and after 1 week 0.05% phenobarbital (PB) was provided with drinking water. Membrane fractional lipid composition showed that the content of cholesterol was higher in 50 group than CO group and also significantly decreased by d-limonene. The content of phospholipid was increased by carcinogen treatment but not affected by dietary oils or d-limonene. Membrane C/PL molar ratio was significantly decreased by d-limonene or carcinogen treatment in 50 groups but not in CO groups. Fatty acid composition was changed by dietary oils but not by carcinogen treatment or d-limonene. Cytosolic PKC activity was not significantly different by dietary oils, d-limonene or carcinogen treatment. However, membrane PKC activity was significantly increased by carcinogen treatment and decreased by d-limonene. Cytosolic GST activity was affected by d-limonene or carcinogen treatment in all dietary groups. These data indicate that dietary oils, d-limonene and carcinogen treatment can not change much membrane phospholipid composition. But membrane C/PL molar ratio was changed by carcinogen treatment and d -limonene although the effect was different between dietary oils. Therefore, it is suggested that different dietary oils and d-limonene can somewhat modulate the changes of membrane fluidity and activities of membrane bound enzymes like membrane associated PKC during carcinogenesis.

Safening Mode of Action of 1, 8-Naphthalic Anhydride on Corn and Soybean Against Herbicide Bensulfuron and Imazaquin (제초제(除草劑) bensulfuron과 imazaquin에 대한 1, 8-naphthalic anhydride(NA)의 옥수수와 콩에 대한 약해경감작용기구(藥害輕減作用機構))

  • Hwang, I.T.;Choi, J.S.;Kim, J.S.;Cho, K.Y.;Chun, J.C.
    • Korean Journal of Weed Science
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    • v.14 no.1
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    • pp.8-15
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    • 1994
  • The mode of safening action and potency of the 1, 8-naphthalic anhydride(NA) were investigated in corn(Zea mays) and soybean(Glycine max) treated with herbicide bensulfuron[2-{{{{{(4,6-dimethoxy-2-pyrimidinyl)amino}carbonyl}amino}sulfonyl}methyl}benzoic acid] and imazaquin[2-{4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl} 3-quinolinonecarboxylic acid]. Seed dressing with 0.2%(w/w) NA showed successful protection in corn against injury from herbicide bensulfuron and imazaquin but not in soybean. Safening factors of NA against bensulfuron and imazaquin were 10.2 and 5.0, respectively, in corn, while they were both 1.3 in soybean. In vivo, Glutathione-S-transferase(GST) activity of NA-treated corn and soybean increased 1.8-and 1.3-fold, respectively, but the activity was not affected by the herbicides in vitro. Acetolactate synthase(ALS) levels of NA-treated corn was increased 1.3-fold, but not changed in soybean. Tolerance of ALS activity to the herbicides was slightly greater in ALS obtained from NA-treated corn than that from the untreated, whereas the difference was not found in soybean. A significant increase of ACCase due to NA occurred in corn, but not in soybean. The herbicides did not affect in vitro ACCase activity.

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Rubus coreanus Extract Attenuates Acetaminophen Induced Hepatotoxicity; Involvement of Cytochrome P450 3A4

  • Lee, Young-Ik;Whang, Kyung-Eun;Cho, Jin-Sook;Ahn, Byung-Min;Lee, Sang-Bum;Dong, Mi-Sook;Kim, Tae-Hyun
    • Biomolecules & Therapeutics
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    • v.17 no.4
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    • pp.455-460
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    • 2009
  • Foods of plant origin, especially fruits and vegetables, have attracted attention because of their potential benefits to human health. In this report, Rubi Fructus (RF), the dried unripe fruit of Rubus coreanus Miq (Rosaceae) and ellagic acid (EA) purified from RF were used to test their potential hepatoprotective effect against acetaminophen (AAP)-induced hepatotoxicity in rats. RF extract (RFext) and EA reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum and the content of lipid peroxide in liver by AAP administration, while the increment of the cellular glutathione (GSH) content and the induction of glutathione S-transferase (GST) and glutathione peroxidase (GSH-PX) which were decreased by AAP administration. RFext and EA from RFext did not affect the two major form of cytochrome P450s, cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A2 (CYP1A2), but downregulated the cytochrome P450 3A4 (CYP3A4) related to the conversion of AAP to N-acetyl-P-benzoquinone imine (NAPQI). These results suggest that RFext and EA from RF exhibit a hepatoprotective effect not only by increasing antioxidant activities but also by down-regulating CYP3A4 in the AAP-intoxicated rat.

The Expression and Functional Analysis of Recombinant Alcohol Dehydrogenase (재조합 alcohol dehydrogenase의 발현 및 기능분석)

  • Kong, Kwang-Hoon;Shim, Eun-Jung;Park, Hee-Joong;Kim, Eun-Ho;Cho, Sung-Hye;Park, Sung-Woo;Kim, Young-Mann
    • Analytical Science and Technology
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    • v.12 no.6
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    • pp.565-570
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    • 1999
  • The alcohol dehydrogenase (ADH) gene from Bacillus stearothermopilus was amplified by the polymerase chain reaction. The amplified DNA was inserted into the expression vector pGEX-KG, and expressed it as a fusion protein with glutathione S-transferase (GST) in E. coli. The recombinant ADH was produced by induction with 1 mM isopropyl-${\beta}$-D-thiogalactopyranoside at $37^{\circ}C$ and purified by glutathione affinity chromatography. The recombinant ADH exhibited high substrate specificity for ethanol. The activity of the recombinant ADH proceeded optimally at pH 9.0 and $70^{\circ}C$. The recombinant ADH was highly stable against high temperature. This thermostable alcohol dehydrogenase can be used for the enzymatic determination of alcohol and for the industrial production of alcohol.

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Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats

  • Jang, Han I;Do, Gyeong-Min;Lee, Hye Min;Ok, Hyang Mok;Shin, Jae-Ho;Kwon, Oran
    • Nutrition Research and Practice
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    • v.8 no.3
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    • pp.272-277
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    • 2014
  • BACKGROUND/OBJECTIVES: This study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats. MATERIALS/METHODS: Sprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection. RESULTS: Although no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC). CONCLUSIONS: Based on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity.

A 43 kD Protein Isolated from the Herb Cajanus indicus L Attenuates Sodium Fluoride-induced Hepatic and Renal Disorders in Vivo

  • Manna, Prasenjit;Sinha, Mahua;Sil, Parames C.
    • BMB Reports
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    • v.40 no.3
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    • pp.382-395
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    • 2007
  • The herb, Cajanus indicus L, is well known for its hepatoprotective action. A 43 kD protein has been isolated, purified and partially sequenced from the leaves of this herb. A number of in vivo and in vitro studies carried out in our laboratory suggest that this protein might be a major component responsible for the hepatoprotective action of the herb. Our successive studies have been designed to evaluate the potential efficacy of this protein in protecting the hepatic as well as renal tissues from the sodium fluoride (NaF) induced oxidative stress. The experimental groups of mice were exposed to NaF at a dose of 600 ppm through drinking water for one week. This exposure significantly altered the activities of the antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and the cellular metabolites such as reduced glutathione (GSH), oxidized glutathione (GSSG), total thiols, lipid peroxidation end products in liver and kidney compared to the normal mice. Intraperitoneal administration of the protein at a dose of 2 mg/kg body weight for seven days followed by NaF treatment (600 ppm for next seven days) normalized the activities of the hepato-renal antioxidant enzymes, the level of cellular metabolites and lipid peroxidation end products. Post treatment with the protein for four days showed that it could help recovering the damages after NaF administration. Time-course study suggests that the protein could stimulate the recovery of both the organs faster than natural process. Effects of a known antioxidant, vitamin E, and a non-relevant protein, bovine serum albumin (BSA) have been included in the study to validate the experimental data. Combining all, result suggests that NaF could induce severe oxidative stress both in the liver and kidney tissues in mice and the protein possessed the ability to attenuate that hepato-renal toxic effect of NaF probably via its antioxidant activity.

Changes of Antioxidant Enzyme Activity in Bagrid Catfish, Pseudobagrus fulvidraco Exposed to Diethylhexyl Phthalate (Diethylhexyl Phthalate에 노출된 동자개, Pseudobagrus fulvidraco의 항산화 효소활성의 변동)

  • KEUM Yoo-Hwa;JEE Jung-Hoon;KOO Ja-Geun;KANG Ju-Chan
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.38 no.5
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    • pp.304-308
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    • 2005
  • The effects of diethylhexyl phthalate (DEHP) on various oxidative stress responses in liver, kidney and gill tissues of freshwater bagrid catfish Pseudobagrus fulvidraco were investigated under laboratory conditions. Bagrid catfish were intraperitoneally injected with sunflower seed oil containing nominal concentrations of 0, 300 or 900mg DEHP per kilogram of body weight for 3 days and the effects after last injection were assessed in liver, kidney and gill tissues of the exposed organisms. The oxidative stress responses of fish were evaluated by analyzing the level of glutathione (GSH), as well as the activities of antioxidant enzymes such as glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR). After exposure to the DEHP, there were significant decrease in GR, GPx activity and GSH content in liver of fish exposed to 900 mg DEHP per kilogram of body weight compared to the control group. Compared with the control group, significant decreases in renal GPx and GR activity were observed in the DEHP treatment groups (900 mg $kg^{-1}$ bw). However, no significant difference was observed in any oxidative stress responses in gills between the DEHP-treated and the untreated group of fish. The findings of the present investigation show that DEHP induce oxidative stress and the liver was the most affected organ followed by the kidney and gills. Furthermore, the changes of GPx and GR activities may be important indicators of oxidative stress responses but additional study is required to confirm the oxidative stress of DEHP.

Taurine Regulates Mitochondrial Function During 7,12-Dimethyl Benz[a]anthracene Induced Experimental Mammary Carcinogenesis

  • Vanitha, Manickam Kalappan;Priya, Kalpana Deepa;Baskaran, Kuppusamy;Periyasamy, Kuppusamy;Saravanan, Dhravidamani;Venkateswari, Ramachandran;Mani, Balasundaram Revathi;Ilakkia, Aruldass;Selvaraj, Sundaramoorthy;Menaka, Rajendran;Geetha, Mahendran;Rashanthy, Nadarajah;Anandakumar, Pandi;Sakthisekaran, Dhanapal
    • Journal of Pharmacopuncture
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    • v.18 no.3
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    • pp.68-74
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    • 2015
  • Objectives: The present study was undertaken to determine the modulatory effect of taurine on the liver mitochondrial enzyme system with reference to mitochondrial lipid peroxidation (LPO), antioxidants, major tricarboxylic acid cycle enzymes, and electron transport chain enzymes during 7,12-dimethyl benz[a]anthracene (DMBA) induced breast cancer in Sprague-Dawley rats. Methods: Animals in which breast cancer had been induced by using DMBA (25 mg/kg body weight) showed an increase in mitochondrial LPO together with decreases in enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), non-enzymic antioxidants (reduced glutathione (GSH), vitamin C, and vitamin E), in citric acid cycle enzymes (isocitrate dehydrogenase (ICDH), alpha ketoglutarate dehydrogenase (alpha KDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH)), and in electron transport chain (ETC) complexes. Results: Taurine (100 mg/kg body weight) treatment decreased liver mitochondrial LPO and augmented the activities/levels of enzymic, and non-enzymic antioxidants, tricarboxylic acid cycle enzymes and ETC complexes. Conclusion: The results of our present study demonstrated the chemotherapeutic efficacy of taurine treatment for DMBA-induced breast carcinomas.