• Nutrition Research and Practice
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• v.11 no.3
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• pp.206-213
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• 2017

BACKGROUN/OBJECTIVES: Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. METHODS/MATERIALS: After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin $F2{\alpha}$ (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. RESULTS: Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly (P < 0.05) lower than those in the HF group without dose-dependent effect. Plasma TBARS concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly (P < 0.05) increased in the HF+BGE 1.0 and HF+BGE 1.5 groups compared to those of the HF group. The mRNA expression levels of hepatic Nrf2, NQO1, HO-1, and GSTA2 were significantly (P < 0.05) increased in the HF with BGE groups compared to those in the HF group. CONCLUSIONS: The improvements of blood glucose homeostasis and antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

• Natural Product Sciences
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• v.22 no.4
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• pp.231-237
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• 2016

Prolonged alcohol consumption causes alcoholic liver damage due to the generation of reactive oxygen species, the accumulation of fatty acids, and an increase in inflammatory cytokines in the liver. In this study, the protective effect of a fruit extract of Paeonia anomala (FEPA) against chronic alcohol-induced liver damage was evaluated in Sprague-Dawley rats fed an ethanol or a control Lieber-DeCarli diet for 5 weeks to induce alcoholic liver damage. FEPA (50, 25, and 10 mg/kg body weight/day) as well as the reference control silymarin (25 mg/kg body weight/day) were administered along with the ethanol diet. FEPA protected against increases in alanine aminotransferase and aspartate aminotransferase in serum and attenuated alcohol-induced increases in triglycerides, tumor necrosis factor alpha, thiobarbituric acid-reactive substances, and cytochrome P450 2E1 enzyme activity in the liver compared with the group treated with ethanol only. Anti-oxidative defenses such as the total glutathione level and glutathione peroxidase activity were increased by FEPA treatment. These results suggest that FEPA exerts protective effects against chronic alcohol-induced liver damage by attenuating hepatosteatosis and pro-inflammatory cytokine production and enhancing anti-oxidative defense mechanisms in the liver.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.3
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• pp.177-183
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• 2000

We examined the neurotoxic effects of 3 glutathione (GSH) depletors, buthionine sulfoximine (BSO), diethyl maleate (DEM) and phorone, under the presence of trolox, cycloheximide (CHX), pyrrolidine dithiocarbamate (PDTC) or MK-801 in primary mouse cortical cell cultures. All three depletors induced neuronal death in dose and exposure time dependent manner, and decreased total cellular GSH contents. The patterns of the neuronal death and the GSH decrements were dependent on the individual agents. DEM $(200\;{\mu}M)$ induced rapid and irreversible decrement of the GSH. BSO (1 mM) also decreased the GSH irreversibly but the rate of decrement was more progressive than that of DEM. Phorone (1 mM) reduced the GSH content to 40% by 4 hr exposure, that is comparable to the decrement of BSO, but the GSH recovered and reached over the control value by 36 hr exposure. BSO showed a minimal neurotoxicity $(0{\sim}10%)$ at the end of 24 hr exposure, but marked neuronal cell death at the end of 48 hr exposure. The BSO (1 mM)-induced neurotoxicity was markedly inhibited by trolox or CHX and partially attenuated by MK-801. DEM induced dose-dependent cytotoxicity at the end of 24 hr exposure. Over the doses of $400\;{\mu}M,$ glial toxicity also appeared. DEM $(200\;{\mu}M)-induced$ neurotoxicity was markedly inhibited by trolox or PDTC. Phorone (1 mM) induced moderate neurotoxicity (40%) at the end of 48 hr exposure. Only CHX showed significant inhibitory effect on the phorone-induced neurotoxicity. These results suggest that the GSH depletors induce neuronal injury via different mechanisms and that GSH depletors should be carefully employed in the researches of neuronal oxidative injuries.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.393-398
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• 2013

Background: Many studies have investigated associations between the glutathione S-transferase M1 (GSTM1) null polymorphism and risk of prostate cancer, but the impact of GSTM1 in people who live in Asian countries is still unclear owing to inconsistencies across results. Methods: We searched the PubMed, Web of Science, Scopus, Ovid and CNKI databases for studies of associations between the GSTM1 null genotype and risk of prostate cancer in people who live in Asian countries, and estimated summary odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: A total of 18 case-control studies with 2,172 cases and 3,258 controls were included in this meta-analysis, which showed the GSTM1 null genotype to be significantly associated with increased risk of prostate cancer in people who live in Asian countries (random-effects OR=1.74, 95% CI1.44-2.09, P<0.001). Similar results were found in East Asians (OR=1.41; 95% CI: 1.12-1.78; P=0.004) and Caucasians in Asia (OR=2.19; 95% CI: 1.85-2.60; P<0.001). No evidence of publication bias was observed. Conclusions: This meta-analysis of available data suggested that the GSTM1 null genotype does contribute to increased risk of prostate cancer in people who live in Asian countries.

• Korean Journal of Veterinary Research
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• v.39 no.4
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• pp.679-688
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• 1999

The combined effects of iron and selenium status on glutathione peroxidase (GSHPx) activity, cytochrome P-450 activity, and lipid peroxidation in the liver and intestinal mucosa of rats were investigated. In experiment one, four experimental groups (+Se+Fe, -Se+Fe, +Se++Fe, -Se++Fe) were manipulated for 3 weeks with intramuscular administration of irondextran (++Fe) and/or normal diet (+Fe) and deionized water (-Se) and/or selenium-supplemented deionized water (+Se). In experiment two, 2% dietary carbonyl iron (instead of the parenteral administration) was fed for 3 weeks to rats. Body weight of rats was significantly decreased in both parenterally and orally iron-overloaded groups (p<0.01), regardless of Se supplement. Serum iron was significantly increased in parenterally iron-overloaded groups but it was marginally increased in orally iron-overloaded groups. There was no significant difference in hemoglobin content among experimental groups in either experiment one or two. Total iron in the small intestine, intestinal mucosa, and livers was significantly high in both parenterally and orally iron-overloaded rats, regardless of selenium status. In the liver and intestine, GSHPx activity was significantly higher in all selenium-supplemented groups, compared to Se-deficient groups (p<0.01) and lipid peroxidation was significantly enhanced in both parenterally and orally iron-overloaded groups, compared to iron-adequate groups. There was no significant difference in cytochrome P-450 activity in the livers between groups in both experiment one and two. These results indicated that GSHPx activity in liver and intestinal mucosa was depended on selenium status, regardless of iron status, and iron-overload enhances lipid peroxidation in liver and intestinal mucosa by increasing the tissue iron content.

• The Korea Journal of Herbology
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• v.25 no.1
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• pp.13-21
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• 2010

Objectives : This study was purposed to the anti-oxidative effects of Polygonati Multiflori Caulis(henceforth PMC) on oxidized brain and liver cells in rats. Methods : After extraction of PMC with water, the water extract was divided into five fractions : hexane, ethyl ether, ethyl acetate, butanol and an aqueous fraction. The phenol contents of each fraction were measured. The lipid peroxidation inhibition effect were then investigated. Results : After processing PCM water and PCM fractionations on oxidized brain cells in rats, the SOD (super oxide dismutase) activity and glutathione content were increased, and the NO (nitric oxide) content was decreased. It had much higher SOD activity than liver cells in rats excluded in the n-BuOH and aqueous fractions. In case of oxidized liver cells in rats, the SOD activity and glutathione content increased, while both the NO content and the MDA (malondialdehyde) content decreased. It had much higher glutathione content than brain cells in rats in the every fractions. It had much lower MDA content than brain cells in rats in the Aqueous fractions and brain cells in rats had much lower MDA content than liver cells in rats in the total extract, n-hexane, EtOEt, EtOAc and n-BuOH fractions. Conclusions : PMC has anti-oxidative effect on oxidized liver cells and brain cells in rats, through there are differences in fraction. Additionally, Anti-oxidative effect of brain cells can be relaxed the mental nerve and it is related PMC effect.

• The Korean Journal of Physiology
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• v.5 no.1
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• pp.43-49
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• 1971

In an attempt to better understand the effect of whole body X-irradiation on the spontaneous motility of the isolated mouse duodenum and to clarify the possible radioprotective notion of reduced glutathione (GSH), a whole body X-irradiation of 1,000r was given to albino mouse either singularly or immediately after injecting GSH intraperitoneally to mouse in the dose of 1mg per gm of body weight. The total length of contraction of the isolated duodenum was recorded on kymograph every five minutes for 60 minutes, and the comparison was made with the control (i.e., normal). The results thus obtained are summarized as follows: 1. The spontaneous motility of the isolated duodenum in the X·irradiated groups showed a significantly elevated pattern for the first 15 minutes comparing with the control. The motility, however, decreased after 15 minutes and remained so in the X-irradiated groups to the level of the non-irradiated control, but 12 hours post-irradiation group showed a significantly increased motility throughout the experiment comparing with the control. 2. When GSH was injected intraperitoneally Prior to the whole body X·irradiation with 1,000r, the spontaneous motility of the isolated duodenum of mouse showed a significantly decreased pattern for the first 10 and 15 minutes comparing with the X·irradiated group followed by the similar motility thereafter comparing with the control and X-irradiated groups. 3. The above results suggest that GSH is effective as a radioprotector in terms of the motility of the isolated mouse duodenum.

• Korean Journal of Plant Tissue Culture
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• v.25 no.4
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• pp.267-271
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• 1998

Cotyledon explants of lettuce were cocultured with Agrobacterium tumefaciens LBA4404::pBKS-GR1 harboring glutathione reductase(GR) gene in MS medium supplemented with 0.1 mg/L NAA and 1.0 mg/L 2ip for 48 hr. These explants were transferred to MS medium supplemented with 0.1 mg/L NAA and 1.0 mg/L 2ip, 50 mg/L kanamycin, and 500 mg/L carbenicillin. After 4 weeks of subculture, kanamycin-resistant shoots were obtained on selection medium. Leaves of putative transformants survived on selection medium containing 100 mg/L kanamycin. Incoporation of the GR gene into lettuce was confirmed by PCR analysis of genomic DNA. Southern blot analysis showed that ECL-labeled GR gene was hybridized to the expected amplified genomic DNA fragment of about 1.8 kb from transgenic lettuce. The presence of mRNA in transgenic lettuce was confirmed by RT-PCR with total RNA of transgenic lettuce. In progeny test of transformants, R$_1$ seeds were resistant to kanamycin (200mg/L) on MS medium.

• Nutrition Research and Practice
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• v.10 no.1
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• pp.26-32
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• 2016

BACKGROUND/OBJECTIVES: It has been shown that vitamin A supplementation has different effects on skeletal health and the antioxidant system. Deficiency or excess of this vitamin can lead to health problems. Vitamin A can work as either an antioxidant or prooxidant depending on its concentration. The present study was conducted to investigate the effects of different doses of vitamin A supplementation on the antioxidant system in rats. MATERIALS/METHODS: Forty Spargue-Dawley male rats were divided into four groups according to the dose of vitamin A received: 0 (A0), 4,000 (A1), 8,000 (A2), and 20,000 (A3) IU retinyl palmitate/kg diet. After a feeding period of 4 wks, lipid peroxide levels, glutathione concentration, antioxidant enzyme activities, and vitamins A and E concentrations were measured. Histopathological changes were observed in rat liver tissue using an optical microscope and transmission electron microscope. RESULTS: Lipid peroxide levels in plasma were significantly decreased in the A1 and A2 groups compared to the A0 rats. Erythrocyte catalase and hepatic superoxide dismutase activities of the A2 group were significantly higher than those of the A0 group. Hepatic glutathione peroxidase activity was significantly lower in the A3 group compared to the other groups. Total glutathione concentrations were significantly higher in the A1 and A2 groups than in the A0 group. Histological examination of liver tissue showed that excessive supplementation of vitamin A might lead to lipid droplet accumulation and nuclear membrane deformation. CONCLUSIONS: These results indicate that appropriate supplementation of vitamin A might have a beneficial effect on the antioxidant system in rats.

• 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.