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

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Association Study of Glutathione-S-Transferase M1/T1 Gene Polymorphism with Deficiency-Excess Differentiation-syndrome in Korean Bronchial Asthmatics (한국인 기관지 천식 환자에서 허설변증과 Glutathione-S-Transferase 유전자의 다형성 연구)

  • Yu, Seung-Ryeol;Jeong, Seung-Yeon;Jung, Ju-Ho;Kim, Jin-Ju;Jung, Sung-Ki
    • The Journal of Internal Korean Medicine
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    • v.28 no.3
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    • pp.453-463
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    • 2007
  • Backgrounds : Glutathione-s-transferase (GST) is a kind of phase II metabolism enzyme and plays an important role in the detoxification of various toxic chemicals. It was reported that the genetic polymorphism of GSTM1 and GSTT1 genes may be responsible for asthma development and susceptibility to allergy. Traditional oriental medicine uses a unique diagnostic technique. differentiation-syndrome. to analyze signs and symptoms of patients synthetically. Through differentiation-syndrome. asthma patients can be divided into two groups: the deficiency syndrome group (DSG) and the excess syndrome group (ESG). Objectives : The purpose of this study was to investigate the possible association of GST gene polymorphism with clinical phenotype by differentiation-syndrome of bronchial asthma patients. Materials and Methods : One hundred and ten participants were evaluated by pulmonary function test. Patients with 53 DSG and 31 ESG by differentiation-syndrome were assessed for genetic analysis. GSTM1 and GSTT1 deletion polymorphism was performed by polymerase chain reaction (PCR). Results : GSTM1 gene deletion was detected in 43.4% of individuals in the DSG and in 38.71 % in the ESG. The distribution of GSTM1 polymorphism between DSG and ESG was not significantly different [$x^2$=0.1767, p=0.6742; OR(95% CI)=1.2139(0.4915-2.9979)]. The proportion of GSTT1 null genotypes was 41.51% in the DGS and 45.16% in the ESG. The distribution of GSTT1 polymorphism between DSG and ESG was also not significantly different [$x^2$=0.1065, p=0.7442; OR(95% CI)=0.8618(0.3525-2.1065)]. In the combined analysis of GSTM1 and GSTT1 genes, the frequency of both null type of GSTM1/GSTT1 genes was not significantly different from both positive type of GSTM1/GSTT1 genes[$x^2$=0.0768, p=0.7817; OR(95% CI)=1.2000(0.3303-4.3602)] Conclusions : These results indicate that polymorphism of the GST gene might not be associated with the symptomatic classification of DSG and ESG by differentiation-syndrome in Korean asthmatics.

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Comparison of Liver Damage in Bromobenzene-Daily Treated Rats with Every Other Day Treated Ones (랫드에 있어서 Bromobenzene의 격일 투여 시, 매일 투여한 경우와 간손상 정도의 비교)

  • 이상희;윤종국;조현국
    • Biomedical Science Letters
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    • v.6 no.2
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    • pp.101-107
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    • 2000
  • To evaluate the effect of intervals of bromobenzene treatment on the liver damage, the bromobenzene (400 mg/kg, i.p.) was given to rats at either one day or two days interval at three times. All the experimental animals were sacrificed at 24 hours after the last injection. Liver morphological changes were observed under a light microscopic examination and liver functional changes were determined by the measurement of alaine aminotransferase (ALT) activity and hepatic malondialdehyde (MDA) content. The experimental to examine the cause of liver damage were cytochrome P45O, glutathione (GSH) content and glutathione S-transferase (GST) activities. The results are summarized as follows; Based on the liver morphological and functional findings, the daily bromobenzene-treated rats (ED) showed the more severe liver damage than every other day bromobenzene-treated rats (EOD). The hepatic cytochrome P45O content was higher in EOD group than that in ED group. And the increasing rate of hepatic GST activity and decreasing rate of GSH content to the control were higher in EOD group than that in ED group. In conclusion, the treatment of bromobenzene intermittently to the rats may lead to more reduced liver injury compared with the continuously treated animals when both cases are treated with the same dose and frequency, and it may be caused by the enhancement of bromobenzene metabolism.

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Different Physiological Activity of Selected Rice Cultivars to Diphenylether Herbicide, Oxyfluorfen - V. Different Content of Antioxidant and GST Activity (Oxyfluorfen에 대한 내성(耐性) 및 감수성(感受性) 벼품종(品種)의 생리활성(生理活性) 기구(機構) - V. 항산화제(抗酸化劑) 함량(含量) 및 GST 활성(活性))

  • Kuk, Y.I.;Guh, J.O.;Park, R.D.
    • Korean Journal of Weed Science
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    • v.16 no.4
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    • pp.327-336
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    • 1996
  • This study was conducted to investigate the content of antioxidant and GST activity of the oxyfluorfen-tolerant and -susceptible rice cultivars with barnyardgrass, a typical susceptible weed in accordance by oxyfluorfen treatment. The content of vitamin C was higher in the tolerant rice cultivar than in the susceptible rice cultivar and barnyardgrass. The contents of vitamin E, carotenoid, glutathione(GSH, GSSG, total glutathione) were not different between the tolerant and susceptible plants. In the case of the content of vitamin C due to the treatment of oxyfluorfen, the tolerant rice cultivars, Hawon and Baru decreased less than the susceptible rice cultivars and barnyardgrass. After the treatment of oxyfluorfen the contents of vitamin E and GSH in the tolerant rice cultivars were higher than in the susceptible rice cultivars or barnyardgrass. But in the content of carotenoid was greater in the tolerant rice cultivars than in the susceptible rice cultivars but they didn`t have any difference in comparison with the susceptible barnyardgrass. And there was no difference in the content of GSSG between the tolerant and susceptible plants. When CDNB or oxyfluorfen were used as substrate, the GST activity, was higher in the tolerant rice cultivars than in the susceptible rice cultivars or batnyardgrass. After the treatment of oxyfluorfen the GST activity was not induced in the rice, but was induced in the barnyardgrass. Even after the treatment of acifluorfen, bifenox and oxadiazon the GST activity was not induced in the rice cultivars.

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Protective Effect of Curcumin and Aqueous Extract of Onchengyeum on CCI4-induced Hepatotoxicity

  • SEUNG Keum Ran;JUNG Ki Hwa
    • Biomolecules & Therapeutics
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    • v.13 no.4
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    • pp.232-239
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    • 2005
  • An aqueous extract of oriental herbal composition named Onchengyeum and curcumin, an antioxidant isolated from turmeric (Curcuma Zonga L.) reduced hepatotoxicity induced by carbon tetrachloride ($CCI_4$). Improved liver function was observed by measuring the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine (CRE), total cholesterol (T-CHO), triglyceride (TG), low density lipoprotein cholesterol (LDL-CHO), high density lipoprotein cholesterol (HDL-CHO), total protein (TP), albumin (ALB) and total bilirubin (BIL) in serum. Hepatic parameters monitored were levels of cholesterol (CHO), triglyceride (TG), and malondialdehyde (MDA) and activities of cytochrome P450 (CYP), NADPH-CYP reductase, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx). The histopathological examination showed that the treatment of Onchengyeum and curcumin relieved the ballooning degeneration of hepatocytes which had been generated by $CCI_4$. The results suggested that hepatoprotective effects of Onchengyeum and curcumin possibly are due to their promising antioxidative activity.

Protective Effect of Sachungwhan against CCl4-induced Hepatotoxicity

  • Koo, Ja-Young;Jung, Ki-Hwa
    • Biomolecules & Therapeutics
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    • v.14 no.4
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    • pp.207-215
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    • 2006
  • Sachungwhan reduced hepatotoxicity induced by carbon tetrachloride($CCl_4$). Improved liver function was observed by measuring the activities of aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), blood urea nitrogen(BUN), creatinine(CRE), total cholesterol(TCHO), triglyceride(TG), low density lipoprotein cholesterol(LDL-CHO), high density lipoprotein cholesterol(HDL-CHO), total protein(TP), albumin(ALB) and total bilirubin(BIL) in serum. Hepatic parameters monitored were levels of cholesterol(CHO), triglyceride(TG), malondialdehyde(MDA), content of cytochrome P450(CYP), level of glutathione(GSH), and activities of NADPH-CYP reductase, superoxide dismutase(SOD), catalase(CAT), glutathione S-transferase(GST), glutathione reductase(GR), glutathione peroxidase(GPx). The histopathological examination showed that the treatment of Sachungwhan relieved the ballooning degeneration of hepatocytes which had been generated by $CCl_4$. The results suggested that hepatoprotective effects of Sachungwhan possibly are due to their promising antioxidative activity.

Protective Effect of Whagan-Jeon (huaganjian) on Acetaminophen-induced Hepatotoxicity (화간전이 아세트아미노펜에 의한 간독성에 미치는 영향)

  • 박철수;김기열;이채중;안중환;김종대;남경수
    • The Journal of Korean Medicine
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    • v.23 no.3
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    • pp.33-42
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    • 2002
  • Objective : This study was performed to investigate the activity of Whagan-Jeon (huaganjian) in protection against acetaminophen (AAP)-induced hepatotoxicity and the possible mechanisms in vivo. Methods : The following were performed : Serum ALT, depletion of hepatic glutathione (GSH) levels, the microsomal p. nitrophenol hydroxylation activity, microsomal aniline hydroxylation activity, genomic DNA fragmentation and its reversal, hepatic glutathione-S-transferase (GST) activity, and hepatic NAD(P)H:quinone oxidoreductase (QR) activity Results : Whagan-Jeon (huaganjian) protected against AAP-inducedhepatotoxicity by the increase of GSH levels, inhibition of P450 2E1-specific metabolic activities, attenuation of hepatic DNA damage, and induction of GST and QR activities in vivo. Conclusions : In conclusion, Whagan-Jeon (huaganjian) was effective in protection against AAP-induced hepatoxicity.

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Production and characterization of a monoclonal anti-glutathione-S-transferase(GST) antibody

  • You, Je-Kyung;Shin, Chan-Young;Park, Kyu-Hwan;Ko, Kwang-Ho
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.93-93
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    • 1997
  • Analysis of protein is often frustrated by the inability to isolate large amounts of purified protein from a native source. To overcome this problem, fusion protein expression systems such as pGEX system have been widely used. Using pGEX system, the desired protein could be easily obtained in a large amount in E. coli, and then the fusion protein could be used for the study of the function of the given protein. To analyze and purify the GST fusion protein, anti-GST antibody could be used as one of the system of choice. However, the production and characterization of monoclonal anti-GST antibody has not been studied extensively yet. To produce monoclonal anti-GST antibody, GST was purified from E. coli transformed with pGEX-cs, one of the pGEX system and was used as an antigen. The monoclonal antibody was produced by fusion of the immunized spleen cells with SP2-0 myeloma cells. The antibody was characterized by ELISA, western blotting, etc. The monoclonal antibody produced in this study (mAb-GSTA) showed strong and specific immunoreactivity against not only GST but also GST-fusion proteins. Also, mAb-GSTA was successfully used for the immunoaffinity purification of the GST ${\beta}$-Rc.-third intracellular-loop fusion protein. The results of the present study suggest that mAb-GSTA may be used for the identification and purification of GST fusion proteins.

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Effects of lymphocyte DNA damage levels in Korean plant food groups and Korean diet regarding to glutathione S-transferase M1 and T1 polymorphisms (건강한 성인의 glutathione S-transferase M1과 T1 유전자 다형성에 따른 한식에서의 식물성 식품군과 한식의 DNA 손상 감소 효과)

  • Kim, Hyun-A;Lee, Min-Young;Kang, Myung-Hee
    • Journal of Nutrition and Health
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    • v.50 no.1
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    • pp.10-24
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    • 2017
  • Purpose: GST (glutathione S-transferase) M1 and T1 gene polymorphisms are known to affect antioxidant levels. This study was carried out to evaluate genetic susceptibility by measuring the effect of DNA damage reduction in the Korean diet by vegetable food according to GST gene polymorphisms using the ex vivo method with human lymphocytes. Methods: Vegetable foods in the Korean diet based the results of the KNHANES V-2 (2011) were classified into 10 food groups. A total of 84 foods, which constituted more than 1% of the total intake in each food group, were finally designated as a vegetable food in the Korean diet. The Korean diet applied in this study is the standard one-week meals for Koreans (2,000 Kcal/day) suggested by the 2010 Dietary Reference Intakes for Koreans. Ex vivo DNA damage in human lymphocytes was assessed using comet assay. Results: In the Korean food group, the DNA damage protective effect of GSTM1 and GSTT1 was found to be greater in mutant type and wild-type, respectively. and the DNA damage protective effect according to the combined genotype of GSTM1 and GSTT1 was different depending on the food group. On the other hand, in Korean Diet, the DNA damage protective effect appeared to be larger in GSTM1 wild-type than in mutant type and was found to not be affected by GSTT1 genotype. Conclusion: These results can be used as basic data to demonstrate the superiority of the antioxidant function of Korean dietary patterns and food groups. Furthermore, it may be a starting point to begin research on customized antioxidant nutrition according to individual genes.

Induction of Microsomal Epoxide Hydrolase, rGSTA2, rGSTA3/5, and rGSTM1 by Disulfiram, but not by Diethyldithiocarbamate, a Reduced Form of Disulfiram

  • Kim, Sang-Geon;Kim, Hye-Jung
    • Toxicological Research
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    • v.13 no.4
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    • pp.339-347
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    • 1997
  • Disulfiram (DSF) and diethyldithiocarbamate (DDC), a reduced form of DSF, protect the liver against toxicant-induced injury through inhibition of cytochrome P450 2E1. The effect of DSF and DDC on the levels of major hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) expression was comparatively studied, given the view that these enzymes are involved in terminal detoxification events for high energy intermediates of xenobiotics. Treatment of rats with a single dose of DSF (20-200 mg/kg, po) resulted in 2- to 15-fold increases in the mEH mRNA level at 24 hr with the ED$_{50}$ value being noted as 60 mg/kg. The mEH mRNA level was elevated ~15-fold at 24 hr after treatment at the dose of 100 mg/kg, whereas the hepatic mRNA level was rather decreased from the maximum at the dose of 200 mg/kg, indicating that DSF might cause cytotoxicity at the dose. In contrast to the effect of DSF, DDC only minimally elevated the mEH mRNA level at the doses employed. DSF moderately increased the major GST mRNA levels in the liver as a function of dose, resulting in rGSTA2, rGSTA3/5 or rGSTM1 mRNA levels being elevated 3- to 4-fold at 24 hr post-treatment, whereas the rGSTM2 mRNA level was not altered. DDC, however, failed to stimulate the mRNA levels for major GST subunits, indicating that the reduced form of DSF was ineffective in stimulating the GST the expression. The effect of other organosulfides including aldrithiol, 2, 2'-dithiobis(benzothiazole) (DTB), tetramethylthiouram disulfide (TMTD) and allyl disulfide (ADS) on the hepatic mEH and GST mRNA expression was assessed in rats in order to further confirm the increase in the gene expression by other disulfides. Treatment of rats with aldrithiol (100 mg/kg, po) resulted in a 16-fold increase in the mEH mRNA level at 24 hr post-treatment. DTB, TMTD and ADS also caused 5-, 9- and 12-fold increases in the rnRNA level, respectively, as compared to control. Thus, all of the disulfides examined were active in stimulating the mEH gene in the liver. The organosulfides significantly increased the rGSTA2, rGSTA3, rGSTA5 and rGSTM1 mRNA levels at 24 hr after administration. In particular, aldrithiol was very efficient in stimulating the rGSTA and rGSTM genes among the disulfides examined. These results provide evidence that DSF and other sulfides effectively stimulate the mEH and major GST gene expression at early times in the liver and that DDC, a reduced form of DSF, was ineffective in stimulating the expression of the genes, supporting the conclusion that reduced form(s) of organosulfur compound(s) might be less effective in inducing the mEH and GST genes through the antioxidant responsive element(s).

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Pathological Changes in Rats Fed petasites japonicus Maxim II. Immunohistochemical Localization of Cytochrome P4502E1 and GST-P in Liver

  • Jee, Young-Heun;Lee, Cha-Soo;Jeong, Kyu-Shik
    • Korean Journal of Veterinary Pathology
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    • v.1 no.1
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    • pp.33-39
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    • 1997
  • We investigated metabolism and carcinogenesis in livers of Sprague-Dawley rats fed juices and pelleted diets containing Korean native plants petasites japonicus Maxim by evaluating cell localization and expression of cytochrome P450s and GST-P. Anti-cytochrome P450s application in liver sections revealed three to four times increased expression of cytochrome P450E1 immunoreactivity in degenerative hepatocytes when compared to histologically normal hepatocytes. Anti-GST-P in showed positive pren plastic foci as well as in individual hepatocytes randomly scattered throughout all liver sections examined. Additionally GST-P was evident in proliferative endothelial cells and biliary epithelial cells in exposed rat livers. These results suggested that the increased level of cytochrome P4502E1 in affected hepatocytes was a direct consequence of Petasites japonicus toxicity. Further immunoreactivity to anti-GST-P in hepatocytes endothelial cells and biliary epithelial cells indicated a possible preneoplastic effects of Petasites japonicus in Sprague-Dawley rat.

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