• 대한한의학방제학회지
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• 제11권2호
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• pp.135-146
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• 2003

Objectives : Wolguk-whan has been used as a prescription of natural drug for the treatment of stress digestive system disease. Recently, we reported that Wolguk-whan methnol extract (WGWM) exerted a significant protective effect against oxidative damage to the liver of ICR mice. This study was purposed to investigate the effects of Wolguk-whan water extract (WGWW) on liver injury induced by oxidative stress. Methods : In order to investigate the effects of WGWW on acute liver injury, ICR mice were pretreated with WGWW for 6days, starved for 24hrs, and administerated acetamirtophen(500mg/kg, i.p.). In the liver homogenates, lipid peroxide and glutathione(GSH) levels were measured. In addition, activities of hepatic enzyme, such as catalase, glutathione peroxidase(GSH-Px), glutathione S-transferase(GST) were measured in the hepatic mitochondrial and cytosolic fractions. Results : In vivo administeration of WGWW showed effective inhibition of acetaminophen induced lipid peroxidation, and showed elevations of GSH level, catalase, GSH-Px, GST activities. Conclusions : These results suggested that WGWW might suppress the formation of oxidative metabolites, and prevent acetaminophen induced hepatotoxicity.

• Food Science and Biotechnology
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• 제18권1호
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• pp.234-238
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• 2009

Effects of ginseng on in vivo antioxidant capacities with age were studied in rats. All rats were reared in the conventional system. Ginseng-treated rats were supplied with ginseng water extracts (25 mg/kg/day) continuously from 6 weeks of age to spontaneous death. None of the rats showed any discernible adverse effects of treatment with ginseng-containing water. There was no significant difference in body weight (BW) gains with age between treated and control groups. However, ginseng extracts did cause a decrease in the level of serum low density lipoprotein (LDL)-cholesterol, glucose, and thiobarbituric acid reactive substances (TBARS) in the treated rats. The activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase in liver cytosol decreased with age in the control group. However, these enzyme activities were well maintained in the ginseng-treated rats and, especially, catalase and glutathione peroxidase activities were consistently higher than in control rats. The levels of total sulfhydryl group (T-SH) and glutathione reductase (GR) were unchanged, and glutathione-s-transferase (GST) activity gradually decreased with age in both groups. There were no differences in T-SH, GR, or GST between the control and treatment groups. These results indicate that long-term administration of ginseng retards age-related deterioration in some biochemical parameters such as cholesterol, glucose, and lactate dehydrogenase in serum and it has an enhancing effect on antioxidant capacity in the liver.

• Korean Journal of Acupuncture
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• 제20권4호
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• pp.41-52
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• 2003

Objectives : Circii Herba has been used as a natural drug for the treatment of stress digestive system disease. The aim of this study is to investigate the role of Circii Herba aqua-acupuncture solution (CHAS) in experimental oxidative liver injury. Methods : In order to investigate the effects of CHAS on acute liver injury, male ICR mice were pretreated with CHAS(0.2 ml/mouse/day) at the loci of BL18 and CV12 for 6days, starved for 24hrs, and administerated acetaminophen(500 mg/kg, i.p.). After acetaminophen administeration, mice were sacrificed, and the liver was removed, rinsed with ice-cold $1.15{\%}$ KCI buffer, and homogenized at $4^{\circ}C$. Fractions(fraction Ⅰ, Ⅱ, Ⅲ) were isolated by differential centrifugation. Lipidperoxide, total SH, and glutathione(GSH) levels were measured in the Fraction Ⅰ. In addition, activities of hepatic enzyme, such as catalase, glutathione peroxidase(GSH-Px) were measured in the Fraction Ⅱ, and glutathione S-transferase(GST) was measured in the Fraction Ⅲ. Results : In vivo treatment of CHAS(BL18 and CV12) showed effective inhibition of acetaminophen induced lipid peroxidation, and showed elevations of total SH, GSH level, catalase, GSH-Px, GST activities. Conclusions : These results suggested that CHAS might suppress the formation of oxidative metabolites, and prevent acetaminophen induced hepatotoxicity.

• 약학회지
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• 제44권3호
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• pp.283-292
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• 2000

Angelicae gigantis Radix aqua-acupuncture solution (AGRAS) and Angelicae gigantis Radix water-extracted solution (AGRWS) were prepared and tested for their organ toxicities and chemopreventive potentials. The organ-toxicity of AGRAS to male ICR mice was studied by the measurements of glutamic oxaloacetic transaminase (GOT), glutamic pyruvate transaminase (GPT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP-s) activities after injection of AGRAS for 7 days. The activities of GOT GPT and LDH were decreased, but the activity of ALP-s was not changed with AGRAS. When AGRAS was administered once daily for 10 days before the tumor implantation, AGRAS exerted antitumor activity by inhibiting the growth of Ehrich ascites tumor cells (EATC) in viva. The inductions of quinone reductase (QR), glutathione (GSH) and glutathione S-transferase (GST) and inhibition of polyamine metabolism were tested for the chemopreventive potentials of AGRAS and AGRWS. AGRAS was potent inducer of QR activity in murine hepatoma Hepalclc7 cells. In cultured rat Ac2F cells, AGRAS was also significantly induced QR activity GSH levels were increased about 1.3 fold with AGRAS. In addition the activity of GST was increased about 2.5 fold with AGRAS at the concentration of $0.1{\;}{\times}{\;}$. The effects of AGRAS and AGRWS were tested on the growth of Acanthamoeba castellanii. Proliferation of Acanthamoeba castellanii in a broth medium was inhibited by AGRAS and AGRWS at the concentration of $1{\;}{\times}{\;}and{\;}5{\;}{\times}{\;}$, respectively: These results suggest that AGRAS has chemopreventive potential by inducing QR activity increasing GSH and GST levels and inhibition of polyamine metabolism.

• Bulletin of the Korean Chemical Society
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• 제33권12호
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• pp.4169-4172
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• 2012

To elucidate the roles of cysteine residues in rice Phi-class GST F3, in this study, all three cysteine residues were replaced with alanine by site-directed mutagenesis in order to obtain mutants C22A, C73A and C77A. Three mutant enzymes were expressed in Escherichia coli and purified to electrophoretic homogeneity by affinity chromatography on immobilized GSH. The substitutions of Cys73 and Cys77 residues in OsGSTF3 with alanine did not affect the glutathione conjugation activities, showing non-essentiality of these residues. On the other hand, the substitution of Cys22 residue with alanine resulted in approximately a 60% loss of specific activity toward ethacrynic acid. Moreover, the ${K_m}^{CDNB}$ value of the mutant C22A was approximately 2.2 fold larger than that of the wild type. From these results, the evolutionally conserved cysteine 22 residue seems to participate rather in the structural stability of the active site in OsGSTF3 by stabilizing the electrophilic substrates-binding site's conformation than in the substrate binding directly.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2221-2224
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• 2013

The glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of a wide range of chemicals, including important environmental carcinogens, as well as chemotherapeutic agents. In the present study 294 acute leukemia cases, comprising 152 of acute lymphocytic leukemia (ALL) and 142 of acute myeloid leukemia, and 251 control samples were analyzed for GSTM1 and GSTT1 polymorphisms through multiplex PCR methods. Significantly increased frequencies of GSTM1 null genotype (M0), GSTT1 null genotype (T0) and GST double null genotype (T0M0) were observed in the both ALL and AML cases as compared to controls. When data were analyzed with respect to clinical variables, increased mean levels of WBC, Blast %, LDH and significant reduction in DFS were observed in both ALL and AML cases with T0 genotype. In conclusion, absence of both GST M & GST T might confer increased risk of developing ALL or AML. The absence of GST enzyme might lead to oxidative stress and subsequent DNA damage resulting in genomic instability, a hallmark of acute leukemia. The GST enzyme deficiency might also exert impact on clinical prognosis leading to poorer DFS. Hence GST genotyping can be made mandatory in management of acute leukemia so that more aggressive therapy such as allogenic stem cell transplantation may be planned in the case of patients with a null genotype.

• Nutrition Research and Practice
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• 제9권1호
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• pp.49-56
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• 2015

BACKGROUND/OBJECTIVES: Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of reactive oxygen species. This study examines whether daily supplementation of kale juice can modulate blood pressure (BP), levels of lipid profiles, and blood glucose, and whether this modulation could be affected by the GSTM1 and GSTT1 polymorphisms. SUBJECTS/METHODS: 84 subclinical hypertensive patients showing systolic BP over 130 mmHg or diastolic BP over 85 mmHg received 300 ml/day of kale juice for 6 weeks, and blood samples were collected on 0-week and 6-week in order to evaluate plasma lipid profiles (total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol) and blood glucose. RESULTS: Systolic and diastolic blood pressure was significantly decreased in all patients regardless of their GSTM1 or GSTT1 polymorphisms after kale juice supplementation. Blood glucose level was decreased only in the GSTM1-present genotype, and plasma lipid profiles showed no difference in both the GSTM1-null and GSTM1-present genotypes. In the case of GSTT1, on the other hand, plasma HDL-C was increased and LDL-C was decreased only in the GSTT1-present type, while blood glucose was decreased only in the GSTT1-null genotype. CONCLUSIONS: These findings suggest that the supplementation of kale juice affected blood pressure, lipid profiles, and blood glucose in subclinical hypertensive patients depending on their GST genetic polymorphisms, and the improvement of lipid profiles was mainly greater in the GSTT1-present genotype and the decrease of blood glucose was greater in the GSTM1-present or GSTT1-null genotypes.

• 한국콘텐츠학회논문지
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• 제17권7호
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• pp.648-663
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• 2017

아시아인종에서 GSTM1/GSTT1 유전자 다형성과 자가면역질환과 관련된 감수성을 검증하기 위해, 2015년 12월까지 EMBASE, Google, KISS, MEDLINE, PubMed에 발표된 18편의 논문들을 메타분석에 인용하였다. GSTM1/GSTT1 유전자의 null, present 유형을 개별적으로 분석하였다. 전체 인구에서 GST 다형성과 자가면역질환 사이에 연관성이 발견되었다(GSTM1, OR=1.334, 95% CI=1.137-1.567, p=0.000, GSTT1, OR=1.212, 95% CI=1.012-1.452, p=0.037). 아시아인종에서 자가면역질환, 특히 vitiligo와 아토피 피부염(p<0.05)에서 GSTM1 유전자와의 연관성이 있었고, RA와 SLE에서 GSTT1 유전자와의 연관성은 없었다(p>0.05). GSTM1 null 유형과 GSTT1 present 유형은 아시아인종에서 자가면역질환과 연관이 있었다(p<0.05). 자가면역질환과 GSTM1-GSTT1 다형성 조합 null 유형의 빈도는 대조군보다 높았다. 이와 같이, GSTM1-GSTT1 다형성 조합 null 유형이 아시아인종에서 자가면역질환의 위험 인자가 될 수 있다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6475-6479
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• 2013

Objectives: Glutathione S-transferase (GST) isoenzymes play important roles in resistance to cell apoptosis and carcinogenesis. We aimed to establish the relationship between GST expression and the prognosis of upper urinary tract urothelial carcinoma (UTT-UC) in Taiwan. Methods: This study retrospectively reviewed 46 patients with pathologically confirmed UUT-UC at Kaohsiung Medical University Hospital. In each patient, expression of GSTT1 and GSTP1 was compared between urothelial carcinoma and normal urothelial cells by Western blotting. Results: GSTP1 expression in the UUT-UC cells was significantly higher than that in normal urothelial cells (1.6 fold, p<0.001). Expression of GSTT1 was significantly associated with the invasiveness of the carcinoma (p=0.006). Conclusions: In UUT-UC, GSTP1 might be a potential tumor marker, whereas high GSTT1 expression could be used as an indicator of cancer progression. This study is the first to demonstrate potential applications of different GST isoenzymes for biomolecular analysis of UUT-UCs in Taiwan.

• Toxicological Research
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• 제27권4호
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• pp.247-251
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• 2011

To clarify whether inhibitory effect of estrogen on liver tumor is associated with cell proliferation, we investigated its role in diethylnitrosamine (DEN)-induced rat preneoplastic lesions, with time sequenced manners. F344 male rats (n = 90) were divided into three groups at 5 weeks of age. The mini-osmotic pumps providing a continuous infusion of DEN was implanted into the abdominal cavity of each animal in group 1, 2 and 3 at 6 weeks of age. To see the effect of estrogen, pellet containing 1 or 10 ${\mu}g$ of estradiol-3-benzoate (EB) was implanted subcutaneously in the animals of groups 2 or 3, respectively, one week prior to DEN treatment. Ten animals of each group were euthanized at 10, 14 and 18 weeks after DEN treatment. Liver tissues at each time point were fixed in 10% phosphate-buffered formalin and were processed and embedded in paraffin and 5 ${\mu}g$ sections mounted on a silanized slide. Glutathione S-transferase placental form (GST-P) positive foci and 5-bromo-2-deoxyuridine (BrdU) labeling cells were detected at each time point. Area of GST-P positive foci in DEN+EB 1 or 10 ${\mu}g$ group was significantly decreased compared to DEN alone at 14 weeks (p < 0.01 or p < 0.05, respectively) an at 18 weeks (p < 0.05 or p < 0.01, respectively). BrdU index in DEN+EB 1 or 10 ${\mu}g$ groups was significantly decreased compared to DEN alone at 14 weeks and at 18 weeks (p < 0.01). Taken together, we conclude that EB treatment decrease the DEN-induced liver preneoplastic lesions and this may be associated with decrease of cellular proliferation.