• Title/Summary/Keyword: NQO

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Effects of 835-MHz Radiofrequency Radiation on the Chromosomal DNA of Mouse Thymic Lymphoma L5178Y $Tk^{+/-}$ Cells

  • Choi, Jong-Soon;Son, TaeHo;Chang, Sung-Keun;Hong, Sae-Yong
    • Korean Journal of Environmental Biology
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    • v.22 no.4
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    • pp.507-512
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    • 2004
  • This study was focused on the risk assessment of whether radiofrequency electromagnetic fields generated by mobile phone is cytogenetically toxic or not. We conducted the effects of 835-MHz electromagnetic field (EMF) on DNA strand breaks in mouse thymic lymphoma L5178Y $Tk^{+/1-}$ cells using alkaline comet assay. EMF frequency 835-MHz we chosen is one of the most popular communication frequency bands in Korean code-division multiple-access (CDMA) mobile phone system. The cells were exposed to 835-MHz EMF alone or 835-MHz EMF combined with cyclophosamide(CPA) or 4-nitroquinoline-1-oxide (4NQO) at specific absorption rate (SAR) of 4.0 W $kg^{-l}$ for 24 and 48hrs. DNA damage expressed as tail moment was increased more than two-fold after exposure to 835-MHz EMF for 24 and 48hr. In particular, CPA for 48hr and 4NQO for 24 hr enhanced notably the tail moment to 9-fold and 16-fold in the presence of 835-MHz EMF, respectively, compared to each single treatment. From these results, it appears that exposure to CDMA-mobile phone radiation at 835-MHz frequency may potentiate DNA strand breaks of mouse thymic lymphoma L5178Y $Tk^{+/1-}$;cells under the defined conditions of this study.

Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway

  • Ha, Ae Wha;Kim, Woo Kyoung
    • 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.

Luteolin Sensitizes Two Oxaliplatin-Resistant Colorectal Cancer Cell Lines to Chemotherapeutic Drugs Via Inhibition of the Nrf2 Pathway

  • Chian, Song;Li, Yin-Yan;Wang, Xiu-Jun;Tang, Xiu-Wen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2911-2916
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    • 2014
  • Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines, $IC_{50}$s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1). Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and $GST{\alpha}1/2$] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/- mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response.

Mutagenic and Antimutagenic Effects of Hemp Seed Oil Evaluated by Ames Salmonella Testing (삼종실유의 항돌연변이 효과)

  • Jeun, Jung-Ae;Cho, Hee-Joon;Jun, Hee-Jin;Lee, Ji-Hae;Jia, Yao-Yao;Cho, Kyoung-Sang;Kim, Eun-Soo;Lee, Sung-Joon
    • Korean Journal of Food Science and Technology
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    • v.43 no.3
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    • pp.396-400
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    • 2011
  • We examined the in vitro mutagenic and antimutagenic effects of hexane-extracted hemp (Cannabis sativa L. subsp. sativa var. sativa) seed oil (HO) with and without S9-mediated metabolic activation, using the TA98 and TA100 Salmonella Typhimurium strains. The MTT assay revealed no cytotoxicity in HepG2 cells for HO quantities $\leq400g$/mL. In the mutagenicity test, revertant colonies did not exceed spontaneous colonies in number. Colony numbers did not increase in either strain after HO treatment, with or without metabolic activation. HO showed no mutagenic effects and did not induce a mutation in either strain. In the antimutagenicity test, HO reduced the number of mutated colonies induced by 4NQO in both strains. The inhibition rates of HO (TA98, 21-91%; TA100, 21-85%) indicated a potent reduction in mutagenicity induced by 4NQO. HO showed no significant mutagenicity and may have antimutagenic effects, as assessed by Ames testing.

Antimutagenic Effects and Isolation of Flavonoids from Humulus japonicus Extract (환삼덩굴(Humulus japonicus) 추출물의 항돌연변이 효과와 Flavonoid 성분의 분리)

  • Park, Seung-Woo;Kim, Sung-Hwan;Chung, Shin-Kyo
    • Korean Journal of Food Science and Technology
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    • v.27 no.6
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    • pp.897-901
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    • 1995
  • To investigate the physiological activities of Humulus japonicus, we examined the mutagenic and antimutagenic effects of the extract and isolated the flavonoid compounds. The water and methanol extracts of Humulus japonicus did not show the mutagenicity by Ames test in the 0.5-4 mg/plate. The methanol extract showed the antimutagenic effect aganinst Salmonella typhimurium TA98 and TA100 induced by 4-nitro-o-phenylenediamine(NPD) and 4-nitroquinoline-N-oxide(NQO). The hexane fraction showed comparatively higher antimutagenic effect than other solvent fractions from the methanol extract. The 50% inhibition concentration($IC_{50}$) of hexane fraction were 2.0 mg/plate, 0.5 mg/plate in TA98 and TA100 respectively. Quercitrin and luteolin were identified in the ethyl acetate fraction from methanol extract of Humulus japonicus by TLC and HPLC.

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Antimutagenic and Cytotoxic Effects of Allium victorialis Extracts (산마늘 추출물의 항돌연변이원성 및 세포독성 효과)

  • 함승시;최승필;최형택;이득식
    • Food Science and Preservation
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    • v.11 no.2
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    • pp.221-226
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    • 2004
  • This study was carried out to determine the antimutagenic and anticancer effects of Allium victoriolis using Ames test and cytotoxicity. Allium victorialis extracted with ethanol and then further fractionated to chloroform, ethyl acetate and water. The inhibition rate of ethanol extract (200 $\mu\textrm{g}$/plate) of Allium victorialis in the Salmonella typhimurium TA100 strain showed 88.2% against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG). The suppression ratio against 4-nitroquinoline-1-oxide(4NQO) in the Salmonella typhimurium TA98 and TA100 strains showed 76.4% and 83.0%, respectively. The cytotoxicity effects of Allium victorialis extract against the cell lines with human lung carcinoma (A549), human breast adenocarcinoma (MCF-7) and human gastric cacinoma (KATOIII) were inhibited with the increase of extract concentration. The treatment of 0.5 $\mu\textrm{g}$/plate Allium victorialis of ethanol extract showed strong cytotoxicities of 74.2%, 71.3% and 67.4% against A549, MCF-7 and KATOIII, respectively.

Cytoprotective Effect of Makgeolli Lees on Paraquat Induced Oxidative Stress in A549 Cells via Activation of NRF2 and Antioxidant Genes

  • Jeon, Miso;Rahman, Naimur;Kim, Yong-Sik
    • Journal of Microbiology and Biotechnology
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    • v.26 no.2
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    • pp.277-286
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    • 2016
  • Makgeolli lees (ML) has several physiological effects such as antioxidant, antidiabetic, and anticancer properties, but its biological functions have not been determined definitively. Here, we tested whether ML has a cytoprotective effect on paraquat (PQ)-induced oxidative stress in the human lung carcinoma cell line A549. At 0.1 mg/ml ML, viability of PQ-exposed A549 cells was restored by 12.4%, 18.5%, and 48.6% after 24, 48, and 72 h, respectively. ML also reduced production of the intracellular reactive oxygen species (ROS) that were generated by PQ treatment. Further experiments revealed that ML treatment enhanced the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) as well as ARE-GFP reporter activity. ML treatment also effectively increased the expression of NRF2's target genes NAD(P)H dehydrogenase quinone 1 (NQO1) and heme oxygenase 1 (HO-1). Moreover, we found that expression of cytoprotective genes, including glutathione peroxidases (GPXs), superoxide dismutase (SOD1), catalase (CAT), peroxiredoxin 3 (PRDX3), and peroxiredoxin 4 (PRDX4), was greatly enhanced by treatment with ML during PQ exposure. Taken together, the data suggest that treatment of PQ-exposed A549 cells with ML ameliorates cytotoxicity through induction of NRF2 expression and its target genes HO-1, NQO1, and other antioxidant genes. Thus, ML may serve as a functional food applicable to ROS-mediated human diseases.

Antimutagenic Effects of Water Extracts of Persimmon Leaf Tea, Green Tea and Oolong Tea on Reversion and Survival of Selected Salmonella Tester Strains (Salmonella typhimurium Strain TA98, 100에서 감잎차, 녹차, 우롱차 추출물의 돌연변이 억제 효과)

  • 강명희;송현순;이현걸
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.28 no.3
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    • pp.599-606
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    • 1999
  • Water extracts of persimmon leaf tea(PLTE), green tea(GTE) and oolong tea(OTE), at the con centration used for human consumption, were examined for inhibitory effects on the mutagenicity of major classes of dietary and environmental mutagens including indirect acting mutagens, B[ ]P (benzo[ ]pyrene), IQ(2 amino 3 methylimidazo[4,5 f]quinoline), 2 AA(2 aminoanthracene) in the presence of S9 mix and direct acting mutagen, 4 NQO(4 nitroquinoline 1 oxide) without S9 mix, using the modified Ames Salmonella/microsome assay. PLTE, GTE and OTE showed very potent and concentration dependent antimutagenic effects against indirect acting mutagens B[ ]P and IQ. At the maximum concentration(16,200 g/plate) of each tea extract, number of colonies decreased in a dose dependent manner up to 82~100%. Similar inhibition of PLTE, GTE and OTE were seen at higher concentration in the mutagenicity of the 2 AA following an initial increase in the activity at lower concentration. However, the mutagenicity of the direct acting mutagen 4 NQO were not suppressed at lower concentration of the three tea extracts, and higher concentration of the tea extracts enhanced mutagenic activity of the mutagen. There were no differences in the mode of antimutagenesis between PLTE, GTE, and OTE, in both Salmonella typhimurium TA98 and TA100 strains against the same mutagen. In conclusion, the water extracts of persimmon leaf tea, green tea and oolong tea possess marked antimutagenic potential against a variety of important dietary and environmental indirect acting mutagens, but the activity was not observed against the direct acting mutagens. These results suggest that the mode of inhibitory action may not have resulted from direct interaction between tea extracts and the mutagens, but rather from indirect metabolic inactivation of mutagens by tea extracts.

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Desmutagenic Effect of Water Extract from Areca catechu L. on the Mutagenicity of N-Methyl-N-Nitro-N'-Nitrosoguanidinein in E. coli PQ37 (N-methyl-N-nitro-N'-nitrosoguanidine의 변이원성에 대한 빈랑 물 추출물의 돌연변이 억제효과)

  • Wu, Wei Jie;Ahn, Byung-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.20 no.1
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    • pp.16-19
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    • 2012
  • The desmutagenic activity of the water extract of Areca catechu L. on the mutagenicity induced by aflatoxin $B_1$ ($AFB_1$), N-methyl-N-nitro-N'-nitrosoguani-dine (MNNG), mitomycin C (MMC) and 4-nitroquinoline 1-oxide (4-NQO) was studied by using the SOS Chromotest with Escherichia coli PQ37. The inhibition rates of water extract of Areca catechu L. at concentration of $100{\mu}g/assay$ were 41.0%, 47%, 46%, and 32% against $AFB_1$, MNNG, MMC and 4-NQO, respectively. The water extract of Areca catechu L. was separated into methanol soluble and methanol insoluble parts. The methanol insoluble part exhibited higher inhibition effect than the methanol soluble part against the mutagenic activities of MNNG. Step-wise fractionation of methanol insoluble part was done to obtain methanol, ethyl acetate and water fractions. Among these fractions, water fraction had the strongest inhibitory effect of 45.0% against mutagenicities of MNNG. The inhibition rates of aqueous fraction of methanol-insoluble from water extracted Areca catechu L. at concentrations of 1.61, 16.13, 161.29 and $322.58{\mu}g/mL$ were 12.0%, 24.0%, 47.5% and 62.0%, respectively. The water fraction showed the inhibitory effects with dose response against the mutagenic activity induced by MNNG.

An Effects of Enzymatic Browning Reaction Products of Potato on the Antimutagenesis

  • Ham, Seung-Shi;Park, Kun-Pyo;Park, Book-Kil;Deoghwan Oh
    • Preventive Nutrition and Food Science
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    • v.2 no.3
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    • pp.232-235
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    • 1997
  • This study was investigated to determine antimutagenic effects of enzymatic browning reaction products (PEBRPs) obtained by reaction of polyphenol compouns with oxidase extracted from potato. Catechol (Ca) PEBRPs showed the strongeest inhibitor effects with 90% inhibition on benzo-($\alpha$)-pyrene(B($\alpha$)P) induced mutagenesis in Salmonella typhimurium TA98, but he least with40% inhibition on the 2-aminofluorene (2-AF) induced mutagenesis in TA98. The strong antimutagenic activities with 80% inhibition were observed in the presence of 100$\mu\textrm{g}$/plate of hydroquinone(HQ)-PEBRP on the B($\alpha$)P or 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole(Trp-P-1) induced mutagenesis in TA98, whereas HQ-PEBRP showed the least antimutagenic effect on 2-AF-induced mutagenesis. The addition of 100$\mu\textrm{g}$ hydroxyhydroquinone(HHQ)-PEBRP to the plate led to approximately 82% inhibitory effects on 2-AF or Trp-P-1 induced mutagenesis in TA98, whereas the least antimutagenicity was obsrved in the4-nitroquinoline-1-oxide(4-NQO) induced mutagenesis in the presence of 100$\mu\textrm{g}$/plate of HHQ-PEBRP. More than 80% inhibiton were observed in the presence of 200$\mu\textrm{g}$/plate of Pyrogalol(Py)-PEBRP on the B($\alpha$)P or Trp-P-1 induced mutagenesis in TA98, but the least with 38% inhibition on 4-NQO induced mutagenesis in TA98. The results indicate that enzymatic browing reaction products of potato have a strong modulatory effect on mutagen induced mutagenesis in TA98.

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