• Archives of Pharmacal Research
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• v.22 no.2
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• pp.99-107
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• 1999

A series of organosulfur compounds were synthesized with the aim of developing chemopreventive compounds active against hepatotoxicity and chemical carcinogesis. 2-(Allylthio) prazine (2-AP) was effective in inhibiting cytochrome P450 2E1-mediated catalytic activities and protein expression, and in inducing microsomal epoxide hydrolase and major glutathione S-transferases. 2-AP reduced the hepatotoxicity caused by toxicant sand elevated cellular GSH content. Development of skin tumors, pulmonary adenoma and aberrant crypt foci in colon by various chemical carcinogens was inhibited by 2-AP pretreatment. Anticarcinogenic effects of 2-AP at the stage of initiation of tumors were also observed in the aflatoxin B1 ($AFB_1$)-induced three-step medium-term hepatocarcinogenesis model. Reduction of $AFB_1$-DNA adduct by 2-AP appeared to result from the decreased formation of $AFB_1$-8,9-epoxide via suppression of cytochrome P450, while induction of GST 2-AP increases the excretion of glutathione-conjugated $AFB_1$ . 2-AP was a radioprotective agent effective against the lethal dose of total body irradiation and reduced radiation-induced injury in association with the elevation of detoxifying gene expression. 2-AP produces reactive oxygen species in vivo, which is not mediated with the thiol-dependent production of oxidants and that NF-KB activation is not involved in the induction of the detoxifying enzymes. the mechanism of chemoprotection by 2-AP may involve inhibition of the P450-mediated metabolic activation of chemical carcinogens and enhancement of electrophilic detoxification through induction of phase II detoxification enzymes which would facilitate the clearance of activated metabolites through conjugation reaction.

• Fisheries and Aquatic Sciences
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• v.27 no.5
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• pp.314-328
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• 2024

The mechanism for the elimination of xenobiotics undergoes three different phases of reactions in organisms. Among these, glutathione S-transferases (GSTs) are classified as phase II detoxification enzymes, catalyzing the conjugation of electrophilic substrates to glutathione or reduced hydroperoxides. This study aimed to investigate the molecular characteristics, detoxification functions, and immune responses of GST omega (LhGSTO1) and kappa (LhGSTK1) in redlip mullet. The open reading frames of LhGSTO1 (720 bp) and LhGSTK1 (687 bp) encoded proteins of 239 and 228 amino acids, respectively. Sequence analysis revealed that LhGSTO1 and LhGSTK1 possessed GSH-binding sites in their N-terminal domains. Substrate-binding sites in the C-terminal domain were exclusively identified in LhGSTO1. In the tissue-specific transcription profile analysis, both LhGSTO1 and LhGSTK1 were ubiquitously expressed in all tissues of healthy mullets. Temporal expression analysis of LhGSTO1 and LhGSTK1 in the blood showed that their expression was significantly modulated by polyinosinic:polycytidylic (poly I:C), lipopolysaccharide (LPS), and Lactococcus garvieae. Different chemical and cellular assays were performed to assess the detoxification and cellular protective abilities of the two proteins. A substrate specificity test using the recombinant proteins revealed that both proteins possessed specific activity toward 1-chloro-2,4-dinitrobenzene (CDNB). In the disk diffusion assay, the smallest clearance zones were observed for LhGSTO1 and LGSTK1 against CdCl₂. In the cell protection assay, both LhGSTO1 and LhGSTK1 showed significant Cd detoxification ability compared to the control. Collectively, these results demonstrate that GST omega and kappa are involved in host defense against immune stimulants and xenobiotics in redlip mullet.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.11
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• pp.1391-1398
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• 2007

We performed a randomized double-blind placebo-controlled trial to determine whether Laminaria japonica extract (LJE) supplement modulates blood glucose, serum lipids and antioxidant systems in type II diabetic patients. We also measured critical parameters assessing safety in liver and kidney functions after LJE supplement. A total of 37 patients (18 males and 19 females) were randomized to either LJE group or placebo group. The treatment group received four 350 mg of LJE capsules (1.4 g, total) per day for 12 weeks. The placebo group received the same dose of cellulose capsules. Baseline characteristics regarding general life style and dietary intake pattern were similar between the two groups. There were no significant influences of LJE supplement except for waist circumference on anthropometric parameters. As the whole, 12 weeks of LJE supplement resulted in a little decrease in fasting blood glucose (FBG) and glycated hemoglobin (HbA1c), but a significant decrease was not observed. Total cholesterol, LDL-cholesterol and triglyceride concentrations were significantly (p<0.05) lowered in LJE group. The antioxidant enzymes, glutathion peroxidase (GSH-px) and superoxide dismutase (SOD) levels were elevated in the LJE group (p<0.05) compared to the placebo. The increase of these enzymes was associated significantly with the decrease of MDA concentration (p<0.05). Furthermore, LJE supplement showed no adverse effects on the functions of liver and kidney. Findings from this study suggest that LJE supplement can help improve serum lipid status in type II diabetic subjects without adverse effects.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.4
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• pp.669-675
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• 2000

This study investigated the effect of Puerariae Flos (PF; flower of Puerariae plant) and Puerariae Radix (PR; root of Puerariae plant) water extracts on the activities on the activities of ethanol-metabolizing enzymes and free radical generating/scavenging enzymes of brain in ethanol-treated rats. Five groups of male Sprague-Dawley rats were orally administered ethanol (25%, v/v) 5 g/kg body weight/day, and sacrificed 5 weeks post treatment. PF and PR water extracts were supplemented in a diet based on 1.2g (I) or 2.4 g (II) raw PF or PR/kg body weight/day. Alcohol dehydrogenase activity of brain was significantly lowered in PF of PR groups, whereas aldehyde dehydrogenase activity was significantly higher in PR groups than those of control and PF groups. Cytochrome P-450 content, aminopyrine D-methylase and aniline hydroxylase activities were decreased in both PF and PR groups compared to control group. Aldehyde oxidase and xanthine oxidase activities tended to decrease by Puerariae plant extract supplemented goups and degree of decrease predominated in PRI. Superoxide dismutase and glutathione S-transferase activities were increased in PF or PR groups, whereas glutathione peroxidase and catalase activities were significantly decrased by Puerariae plant extracts supplement. These results indicated that supplementation of PF or PR lowers free radical generating enzymes activities. It was suggested that the activities of ethanol metabolizing emzymes and antioxidant enzymes in brain can be enhanced by PF or PR supplement in ethanol-treated rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.1
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• pp.42-56
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• 2005

Hyperlipidemia is one of the risk factors for coronary artery disease. Despite of epidemiological evidence that tea consumption is associated with the reduced risk of coronary heart disease, experimental studies designed to show that drinking tea affects blood lipid concentration or oxidative stress have been unsuccessful. The purpose of this study was to investigate whether functional tea (three servings/day) supplement with medical nutrition therapy (MNT) lead to a beneficial outcomes in mildly hyperlipidemic adults. From February to October, 2003, the 43 hyperlipidemic (23 men, 20 women) subjects (total cholesterol$\geq$200 mg/dL or triglyceride$\geq$150 mg/dL) admitted to K Medical Center were studied. Subjects were randomly divided into 3 groups; placebo tea (PT), half dose of functional tea (HFT), full dose of functional tea (FFT). During 12 weeks of study period, the subjects were given placebo or functional tea daily with MNT. Anthropometric measurements, blood chemical analysis including lipid levels, total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, and dietary assessment were carried out at the beginning and end of experiment. The effects of functional tea were compared with the placebo in randomized clinical trial study. The placebo was prepared to match with the functional tea in color and taste. After the 12 weeks of MNT, the subjects had regular and balanced meal pattern. Consumption of foods high in cholesterol and saturated fat, salty foods, fried foods, and instant foods decreased significantly in all three groups (p<0.05). Intake of energy and cholesterol also decreased (p<0.05). Drinking three servings per day (390 mL/day) of functional tea significantly reduced the levels of blood triglyceride (HFT, 42.5%; FFT, 29.4%), total cholesterol (HFT, 8.5%; FFT, 13.7%), and atherogenic index (HFT, 14.6%; FFT, 21.7%). Whereas no changes were found in the LDL-, HDL-cholesterollevels, and LDL/HDL ratio. Plasma homocysteine (Hcy) concentration decreased significantly (p<0.05) in functional tea groups (HFT, 14.9%; FFT, 14.1%). SOD increased significantly (p<0.05) in HFT (8.3%). GSH-Px increased significantly (p<0.05) in FFT (12.8%). In conclusion, the MNT improved the dietary habits, in addition, functional tea supplement decreased blood lipid levels and Hcy, and increased SOD and GSH-Px levels. These results indicate that functional tea consumption may decrease the risk of cardiovascular disease via improving blood lipid levels and antioxidant status.

• Journal of Pharmacopuncture
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• v.5 no.2
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• pp.76-91
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• 2002

The lipid lowering and antioxidant effects of Gansoo(BL18), Pungji(GB20) and Eumnungcheun(SP9) acupuncture in rats fed high fat diet were analyzed in biochemical and molecular biological aspects. The results obtained from this study are as follows : 1. In the body weight reduction, all acupuncture groups showed a high reduction compared to those of control group and in acupuncture groups, Gansoo(BL18) and Pungji(GB20) acupuncture groups showed a high reduction. 2. The concentration of plasma triglyceride, total cholesterol and LDL-cholesterol with acupuncture groups showed a little decrease and in acupuncture groups, Gansoo(BL18) and Pungji(GB20) groups showed a low values compared to those of other acupuncture groups. However, the tendency of HDL-cholesterol concentration showed no significant different. 3. The concentration of plasma ${\beta}-lipoprotein$ and free fatty acids showed a lowest values in the Gansoo(BL18) and Pungji(GB20) acupuncture groups and the glucose concentration showed to decrease in all treated acupuncture groups. 4. The concentration of liver total cholesterol and triglyceride in Gansoo(BL18) and Pungji(GB20) acupuncture groups showed a lower values than those of control group. 5. In all the acupuncture groups, the plasma glutamic oxaloacetic transaminase(GOT) activity showed a little decrease. In the glutamic pyruvate activity(GPT), Gansoo(BL18) and Pungji(GB20) acupuncture groups showed a lower values than those of control groups. However the values of eumneungcheun acupuncture only group showed no significant difference to those of control group. 6. The plasma and liver Thiobabituric acid reactive substance (TBARS) concentration in Gansoo(BL18) and Pungji(GB20) acupuncture groups were a lower than those of control group. However the values of eumneungcheun acupuncture group showed no significant difference to control group. 7. The superoxide dismutase (SOD) activity in Gansoo(BL18) acupuncture group and Glutathione peroxidase (GSH-Px) activity in Gansoo(BL18) and Pungji(GB20) acupuncture groups showed a high values. The catalase (CAT) activity in all the acupuncture groups showed a higher values than those of control group. 8. In acupuncture groups, DNA expression of Apo-B and Apo-E showed a tendency to decrease, however DNA expression of leptin showed no significant difference in all treatment groups. DNA expression of $TNF-{\alpha}$ showed a increase in acupuncture groups. These results indicate that Gansoo(BL18) and Pungji(GB20) (especially Gansoo(BL18)) acupuncture affect the lipid metabolism and showed possibility of lowering adipose tissue mass and lipid peroxidation.

• Nutrition Research and Practice
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• v.11 no.3
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• pp.214-222
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• 2017

BACKGROUND/OBJECTIVES: Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of xenobiotics by conjugating substances with glutathione. The aim of this study is to assess the antioxidative status and the degree of DNA damage in the subclinical hypertensive patients in Korea using glutathione S-transferase polymorphisms. SUBJECTS/METHODS: We examined whether DNA damage and antioxidative status show a difference between GSTM1 or GSTT1 genotype in 227 newly diagnosed, untreated (systolic blood pressure $(BP){\geq}130mmHg$ or diastolic $BP{\geq}85mmHg$) subclinical hypertensive patients and 130 normotensive subjects (systolic BP < 120 mmHg and diastolic BP < 80 mmHg). From the blood of the subjects, the degree of the DNA damage in lymphocyte, the activities of erythrocyte superoxide dismutase, the catalase, and the glutathione peroxidase, the level of glutathione, plasma total radical-trapping antioxidant potential (TRAP), anti-oxidative vitamins, as well as plasma lipid profiles and conjugated diene (CD) were analyzed. RESULTS: Of the 227 subjects studied, 68.3% were GSTM1 null genotype and 66.5% were GSTT1 null genotype. GSTM1 null genotype had an increased risk of hypertension (OR: 2.104, CI: 1.38-3.35), but no significant association in GSTT1 null genotype (OR 0.982, CI: 0.62-1.55). No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and plasma TRAP, CD, lipid profiles, and GSH levels were observed between GSTM1 or GSTT1 genotype. Plasma levels of ${\alpha}-tocopherol$ increased significantly in GSTT1 wild genotype (P < 0.05); however, plasma level of ${\beta}-carotene$ increased significantly in GSTT1 null genotype (P < 0.01). DNA damage assessed by the Comet assay was significantly higher in GSTM1 null genotype than wild genotype (P < 0.05). CONCLUSIONS: These results confirm the association between GSTM1 null genotype and risk of hypertension as they suggest that GSTM1 null genotype leads to an increased oxidative stress compared with wild genotype.

• BMB Reports
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• v.38 no.5
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• pp.609-618
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• 2005

$\gamma$-Glutamyl transpeptidase (GGT, EC 2.3.2.2.) catalyzes the transfer of the $\gamma$-glutamyl moiety from $\gamma$-glutamyl containing ompounds, notably glutathione (GSH), to acceptor amino acids and peptides. A second gene (GGTII) encoding GGT was previously isolated and characterized from the fission yeast Schizosaccharomyces pombe. In the present work, the GGTII-lacZ fusion gene was constructed and used to study the transcriptional regulation of the S. pombe GGTII gene. The synthesis of $\beta$-galactosidase from the GGTII-lacZ fusion gene was significantly enhanced by NO-generating SNP and hydrogen peroxide in the wild type yeast cells. The GGTII mRNA level was increased in the wild-type S. pombe cells treated with SNP. However, the induction by SNP was abolished in the Pap1-negative S. pombe cells, implying that the induction by SNP of GGTII is mediated by Pap1. Fermentable carbon sources, such as glucose (at low concentrations), lactose and sucrose, as a sole carbon source, enhanced the synthesis of $\beta$-galactosidase from the GGTII-lacZ fusion gene in wild type KP1 cells but not in Pap1-negative cells. Glycerol, a non-fermentable carbon source, was also able to induce the synthesis of $\beta$-galactosidase from the fusion gene, but other non-fermentable carbon sources such as acetate and ethanol were not. Transcriptional induction of the GGTII gene by fermentable carbon sources was also confirmed by increased GGTII mRNA levels in the yeast cells grown with them. Nitrogen starvation was also able to induce the synthesis of $\beta$-galactosidase from the GGTII-lacZ fusion gene in a Pap1-dependent manner. On the basis of the results, it is concluded that the S. pombe GGTII gene is regulated by oxidative and metabolic stress.

• Korean Journal of Environmental Biology
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• v.26 no.2
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• pp.94-101
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• 2008

The aim of this study was to assess the responses of mixed function oxygenase (MFO) and antioxidative systems of feral Javelin goby, Acanthogobius hasta, caught in two sites of different pollution level in Shihwa lake, which has been a highly polluted lake by organic pollutants from nearby industrial complexes and sites. Enzymes analyzed in phase I of MFO system are cytochrome P450 (CYP), NADPH-cytochrome P450 reductase (P450R), NADH-cytochrome b5 reductase (b5R), and ethoxyresorufin deethylase (EROD). Phase II enzyme of glutathione S-transferase (GST) in MFO system was also investigated. Moreover, oxidative-enzyme system including catalase (CAT), glutathione reductase (GR) and total-glutathione peroxidase (GPX) activities and glutathione concentration in both of oxidized (GSSG) and reduced form (GSH) were determined. P450R, b5R, and GST activities of fish are relatively high in the polluted area, whereas hepatic EROD activity levels of fish in polluted area were lower than those of unpolluted area. CYP concentrations are not different between areas. These results indicated that feral Acanthogobius hasta were adaptive to highly polluted environment and exposed to oxidative stress in Shihwa lake.