• YAKHAK HOEJI
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• v.51 no.6
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• pp.383-388
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• 2007

It has been reported that sulfur-containing intermediates or products in the transsulfuration pathway including S-adenosylmethionine, 5'-methylthioadenosine, glutathione and taurine can prevent liver injury mediated by inflammation response induced by lipopolysaccharide (LPS) treatment. The present study examines the modulation of hepatic metabolism of sulfur amino acid in a model of acute sepsis induced by LPS treatment (5 mg/kg, iv). Serum TNF-alpha and hepatotoxic parameters were significantly increased in rats treated with LPS, indicating that LPS results in sepsis at the doses used in this study. LPS also induced oxidative stress determined by increases in malondialdehyde levels and decreases in total oxy-radical scavenging capacities. Hepatic methionine and glutathione concentrations were decreased, but S-adenosylho-mocysteine, cystathionine, cysteine, hypotaurine and taurine concentrations were increased. Hepatic protein expression of methionine adenosyltransferase, cystathionine beta-synthase and cysteine dioxygenase were induced, but gamma-glutamylcysteine ligase catalytic subunit levels were decreased. The results show that sepsis activates transsulfuration pathway from methionine to cysteine, suggesting an increased requirement for methionine during sepsis.

• Journal of Korean Neurosurgical Society
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• v.60 no.3
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• pp.355-361
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• 2017

Objective : The aim of this study to investigate the normal values of erythropoietin (EPO) and neuroprotective effects of quercetin and mannitol on EPO and hematocrit levels after acute severe traumatic brain injury (TBI) in rat model. Methods : A weight-drop impact acceleration model of TBI was used on 40 male Wistar rats. The animals were divided into sham (group I), TBI (group II), TBI+quercetin (50 mg/kg intravenously) (group III), and TBI+mannitol (1 mg/kg intravenously) (group IV) groups. The malondialdehyde, glutathione peroxidase, catalase, EPO, and hematocrit levels were measured 1 and 4 hour after injury. Two-way repeated measures analysis of variance and Tukey's test were used for statistical analysis. Results : The malondialdehyde levels decreased significantly after administration of quercetin and mannitol compared with those in group II. Catalase and glutathione peroxidase levels increased significantly in groups III and IV. Serum EPO levels decreased significantly after mannitol but not after quercetin administration. Serum hematocrit levels did not change significantly after quercetin and mannitol administration 1 hour after trauma. However, mannitol administration decreased serum hematocrit levels significantly after 4 hour. Conclusion : This study suggests that quercetin may be a good alternative treatment for TBI, as it did not decrease the EPO levels.

• Preventive Nutrition and Food Science
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• v.7 no.3
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• pp.238-244
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• 2002

Protective effect of skin by antioxidative dietary buchu (Chinese chives, Allium tuberosum Router), was evaluated in ICR mice fed diets containing 2% or 5% buchu for 12 months. Lipid peroxidation and protein oxidation in skin, with or without ultraviolet B (UVB) irradiation, activities of antioxidative enzymes, total glutathione concentrations, and non-soluble collagen contents were measured. Dietary buchu decreased significantly in TBARS and protein carbonyl levels in skin compared to the control group, and were lower in those fed 5% than 2% buchu diet group. ICR mice exhibited an age-dependent decrease in antioxidative enzyme activities and total glutathione concentrations on the control diet, but in the groups fed buchu diet the enzyme activities and glu-tathione concentrations remained at youthful levels for most of the study. SOD, glutathione peroxidase, and catalase activities as well as total glutathione concentrations increased with time in the skins of the mice fed buchu diets. Lipid peroxidation and protein oxidation provoked by UVB irradiation on ICR mice skin homogenates were also significantly inhibited by dietary buchu. The buchu diets also decreased the formation of non-soluble collagen in mice skin, compared to the control group. These results suggest that antioxidative components and sulfur-compounds in buchu may confer protective effect against oxidative stress resulting from aging and exposure to ultraviolet irradiation.

• Toxicological Research
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• v.17
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• pp.251-256
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• 2001

The expression of phase II detoxifying enzymes is affected by a variety of compounds and the induction of the enzymes plays an essential role in chemoprevention. A variety of phytochemicals such as sulfur-containing chemoprotective agents (SCC) may trigger cellular signals and activate phase II gene expression through ARE activation. see induces glutathione S-transferases. Studies were conducted to investigate the role of mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase (PI3-kinase) in the induction of GST (e.g. rGSTA2) by sec. We also studied the MAP kinase pathway responsible for the GST expression by see and compared that with the pathway activated by oxidative stress as a result of sulfur amino acids deprivation (SAAD). see inhibited phosphorylation of ERK1/2 although the effect of see on JNK and p38 MAP kinase was minimal. Wortmannin and LY294002. PI3-kinase inhibitors. abolished the increases in rGSTA2 mRNA and protein levels by SCC. Deprivation of cystine and methionine caused oxidative stress in H4IIE cells. as evidenced by a decrease in the reduced glutathione and an increase in prooxidant production. Electrophoretic mobility shift assay revealed that the ARE complex consisting of Nrf-1/2 and Maf proteins was activated 12~48 h. The rGSTA2 mRNA and protein levels were increased by SAAD. Activation of ARE and induction of rGSTA2 were both completely inhibited by PI3-kinase inhibitors. Inhibition of p38 MAP kinase by SB203580 prevented the ARE-mediated rGSTA2 induction. The results of this study showed that PI3-kinase might play an essential role in the ARE-mediated rGSTA2 induction by see or SAAD and that the dual MAP kinase pathways were responsible for the enzyme induction.

• Journal of Life Science
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• v.9 no.6
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• pp.684-691
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• 1999

Gamdutang aqua-acupuncture solution (GAS), Gamdutang water-extracted solution (GWS) and Dae-Gamdutang aqua-acupuncture solution (DGAS) were prepared and tested for chemopreventive potentials. GAS was potent inducer of quinone reductase (QR) activity in Heapa1c1c7 murine hepatoma cells in culture, whereas GWS is less potent. GAS, GWS and DGAS were significantly induced QR activity in cultured rat normal liver cell, Ac2F. Glutathione (GSH) levels were increased about 1.8, 1.0 and 1.1 fold with GAS, GWS and DGAS in Hepa1c1c7 cells, respectively. In addition glutathione S-transferase (GST) activity was increased with GAS, GWS and DGAS. The effects of GAS, GWS and DGAS on the growth of Acanthamoeba castellanii were tested. Proliferation of A. castellanii was inhibited by GAS, GWS and DGAS at concentrations of 1 $\times$ and 5$\times$. These results suggest that GAS has chemopreventive potential by inducing QR and GST activities, increasing GSH levels and inhibition of polyamine metabolism.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6403-6407
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• 2012

Detoxifying enzymes are present in most epithelial cells of the human gastrointestinal tract where they protect against xenobiotics which may cause cancer. Induction of examples such as glutathione S-transferase (GST) and its thiol conjugate, glutathione (GSH) as well as NAD(P)H: quinoneoxidoreductase (NQO1) facilitate the excretion of carcinogens and thus preventing colon carcinogenesis. Pterostilbene, an analogue of resveratrol, has demonstrated numerous pharmacological activities linked with chemoprevention. This study was conducted to investigate the potential of pterostilbene as a chemopreventive agent using the HT-29 colon cancer cell line to study the modulation of GST and NQO1 activities as well as the GSH level. Initially, our group, established the optimum dose of 24 hours pterostilbene treatment using MTT assays. Then, effects of pterostilbene ($0-50{\mu}M$) on GST and NQO1 activity and GSH levels were determined using GST, NQO1 and Ellman assays, respectively. MTT assay of pterostilbene ($0-100{\mu}M$) showed no cytotoxicity toward the HT-29 cell line. Treatment increased GST activity in the cell line significantly (p<0.05) at 12.5 and $25.0{\mu}M$. In addition, treatment at $50{\mu}M$ increased the GSH level significantly (p<0.05). Pterostilbene also enhanced NQO1 activity significantly (p<0.05) at $12.5{\mu}M$ and $50{\mu}M$. Hence, pterostilbene is a potential chemopreventive agent capable of modulation of detoxifiying enzyme levels in HT-29 cells.

• YAKHAK HOEJI
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• v.44 no.3
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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.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5071-5074
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• 2016

Background: Azoxymethane (AOM) is a well-known colon cancer-inducing agent in experimental animals via mechanisms that include oxidative stress in rat colon and liver tissue. Few studies have investigated AOM-induced oxidative stress in rat liver tissue. Red seaweeds of the genera Hypnea Bryodies and Melanothamnus Somalensis are rich in polyphenolic compounds that may suppress cancer through antioxidant properties, yet limited research has been carried out to investigate their anti-carcinogenic and antioxidant influence against AOM-induced oxidative stress in rat liver. Objective: This study aims to determine protective effects of red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts against AOM-induced hepatotoxicity and oxidative stress. Materials and Methods: Sprague-Dawley rats received intraperitoneal injections of AOM, 15 mg/kg body weight, once a week for two consecutive weeks and then orally administered red seaweed (100 mg/kg body-weight) extracts for sixteen weeks. At the end of the experiment all animals were overnight fasted then sacrificed and blood and liver tissues were collected. Results: AOM treatment significantly decreased serum liver markers and induced hepatic oxidative stress as evidenced by increased liver tissue homogenate levels of nitric oxide and malondialdehyde, decreased total antioxidant capacity and glutathione, and inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and superoxide dismutase). Both red seaweed extracts abolished the AOM-associated oxidative stress and protected against liver injury as evidenced by increased serum levels of liver function markers. In addition, histological findings confirmed protective effects of the two red seaweed extracts against AOM-induced liver injury. Conclusion: Our findings indicate that red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts counteracted oxidative stress-induced hepatotoxicity in a rat model of colon cancer.

• Fisheries and Aquatic Sciences
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• v.17 no.3
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• pp.345-353
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• 2014

Copper has been widely used to control algae and pathogens in fish culture ponds. However, its toxic effects on fish depend not only on its concentration in the water but also on the water quality. A laboratory experiment was conducted to assess copper toxicity in the black rockfish Sebastes schlegeli using a panel of antioxidant enzymes, including glutathione (GSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD), at different levels of copper at three water temperatures (WT, 18, 23, $28^{\circ}C$) for 4 days. After exposure to two copper concentrations (100 and $200{\mu}g/L$), GSH levels and GST activities increased significantly, depending on WT (P < 0.05) in the liver, gill, and kidney of the black rockfish. GPx and SOD activities decreased significantly with both increasing WT and copper treatment in the organs of black rockfish (P < 0.05). These changes can be seen as initial responses to temperature stress and as a sustained response to copper exposure. This also indicates that GSH and related enzymes activities were sensitive indexes to stress by toxicants such as copper. The present findings suggest that simultaneous stress due to temperature change and copper exposure can accelerate changes in enzymes activities in the black rockfish. This provides another example of synergism between environmental temperature and pollutants, which may have important implications for the survival of fish in polluted environments during seasonal warming and/or global climate change.

• Archives of Pharmacal Research
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• v.24 no.2
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• pp.114-118
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• 2001

The present study was undertaken to investigate whether or not the hepatoprotective activity of acetylbergenin was superior to bergenin in carbon tetrachloride ($CCl_4$)-intoxicated rat. Acetylbergenin was synthesized by acetylating bergenin, which was isolated from Mallotus japonicus. The hepatoprotective effects of acetylbergenin were examined against $CCl_4$-induced liver damage in rats by means of serum and liver biochemical Indices. Acetylbergenin was administered orally once daily for 7 successive days, then a 0.5 ${m/kg}$ mixture of $CCl_4$in olive oil (1:1) was intraperitoneally injected at 12 h and 36 h after the final administration of acetylbergenin. Pretreatment with acetylbergenin reduced the elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and $\gamma$-glutamyltransferase in a dose dependent fashion. Acetylbergenin also prevented the elevation of hepatic malondialdehyde formation and depletion of glutathione content dose dependently in $CCl_4$-intoxicates rats. In addition, the decreased activities of glutathione S-transferase and glutathione reductase were restored to almost normal levels. The results of this study strongly suggest that acetylbergenin n has potent hepatoprotective activity against $CCl_4$-induced hepatic damage in rats by glutathione-mediated detoxification as well as having free radical scavenging activity. In addition, acetylbergenin doses of 50 ${mg/kg}$showed almost the same levels of hepatoprotection activity as 100 ${mg/kg}$ of bergenin, indicating that lipophilic acetylbergenin is more active against the antihepatotoxic effects of $CCl_4$ than those of the much less lipophilic bergenin.