• Title/Summary/Keyword: oxidative DNA damage

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A plant-based multivitamin, multimineral, and phytonutrient supplementation enhances the DNA repair response to metabolic challenges

  • Yeo, Eunji;Hong, Jina;Kang, Seunghee;Lee, Wonyoung;Kwon, Oran;Park, Eunmi
    • Journal of Nutrition and Health
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    • v.55 no.4
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    • pp.450-461
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    • 2022
  • Purpose: DNA damage and repair responses are induced by metabolic diseases and environmental stress. The balance of DNA repair response and the antioxidant system play a role in modulating the entire body's health. This study uses a high-fat and high-calorie (HFC) drink to examine the new roles of a plant-based multivitamin/mineral supplement with phytonutrients (PMP) for regulating the antioxidant system and cellular DNA repair signaling in the body resulting from metabolic stress. Methods: In a double-blind, randomized, parallel-arm, and placebo-controlled trial, healthy adults received a capsule containing either a PMP supplement (n = 12) or a placebo control (n = 12) for 8 weeks. Fasting blood samples were collected at 0, 1, and 3 hours after consuming a HFC drink (900 kcal). The blood samples were analyzed for the following oxidative stress makers: areas under the curve reactive oxygen species (ROS) levels, plasma malondialdehyde (MDA), erythrocytes MDA, urinary MDA, oxidized low-density lipoprotein, and the glutathione:oxidized glutathione ratio at the time points. We further examined the related protein levels of DNA repair signaling (pCHK1 (Serine 345), p-P53 (Serine 15), and 𝛄H2AX expression) in the plasma of subjects to evaluate the time-dependent effects of a HFC drink. Results: In a previous study, we showed that PMP supplementation for eight weeks reduces the ROS and endogenous DNA damage in human blood plasma. Results of the current study further show that PMP supplementation is significantly correlated with antioxidant defense. Compared to the placebo samples, the blood plasma obtained after PMP supplementation showed enhanced DNA damage response genes such as pCHK1(Serine 345) (a transducer of DNA response) and 𝛄H2AX (a hallmark of DNA damage) during the 8 weeks trial on metabolic challenges. Conclusion: Our results indicate that PMP supplementation for 8 weeks enhances the antioxidant system against oxidative stress and prevents DNA damage signaling in humans.

Inhibition Effects on Oxidative DNA Damage and Anti-inflammatory Effects of Nelumbinis Flos (연꽃의 산화적 DNA 손상 억제 활성 및 항염증 효과)

  • Jeong, Hyung Jin;Park, Yeon Gyeong;Jang, Tae Won;Kim, Do Wan;Jeong, Jin Boo;Park, Jae Ho
    • The Korea Journal of Herbology
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    • v.32 no.3
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    • pp.45-53
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    • 2017
  • Objective : Nelumbo nucifera, its rhizome and semen have been used as a traditional medicine which was studied on antioxidant, hepatoprotective effect, anti-obesity and the others. However, Nelumbinis Flos have not studied. We investigated protective effects on oxidative DNA damage and anti-inflammatory effects of Nelumbinis Flos. Methods : The antioxidant activity was conducted by 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical, 2, 2'-Azino-bis (3-ethylbenzothiazoline-6 sulfonic acid) diammonium salt (ABTS) radical scavenging assay and reducing power assay. Total phenolic content was analyzed. Also, phenolic compounds were detected by HPLC/UV. The inhibitory effect on oxidative DNA damage was determined using ${\Phi}X-174$ RF I plasmid DNA cleavage assay. The anti-inflammatory effect of Nelumbinis Flos was measured by the amount of nitric-oxide (NO) produced and protein levels of iNOS, and COX-2 in LPS induced RAW 264.7 cells. Results : The results of DPPH and ABTS radical scavenging activity at $200{\mu}g/m{\ell}$ of extraction were $97.02{\pm}0.88%$ and $96.42{\pm}0.25%$. Reducing power (fold of L-ascorbic acid as control) was $100.14{\pm}0.31$ at $200{\mu}g/m{\ell}$. Total phenol content was $8.70{\pm}0.02mg/g$. Chlorogenic acid, catechin and epicatechin were found by HPLC. Nelumbinis Flos has inhibitory effect in dose-manner against oxidative DNA damage. In addition, it showed the anti-inflammatory effect by suppression of NO production as well as protein levels of iNOS, and COX-2. Conclusion : This study suggested that Nelumbinis Flos showed potential antioxidant and suppression activities of various factors were related in NO produced. Therefore, Nelumbinis Flos as natural plant resources that may help reduce inflammation and alleviate DNA damage.

Inhibitory Effect of the Phenolic Compounds from Apples Against Oxidative Damage and Inflammation

  • Sim, Jang-Seop;Jeong, Jin-Boo;Lee, Jong-Hwa;Kwon, Tae-Hyung;Cha, Young-Joon;Jeong, Hyung-Jin
    • Korean Journal of Plant Resources
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    • v.23 no.6
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    • pp.487-497
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    • 2010
  • ROS have been associated with pathogenic processes including carcinogenesis through direct effect on DNA and play an important role in the pathogenesis of inflammation. Because of many types of phenolic acid derivatives and flavonoids, apples have been one of the human diet since ancient times and are one of the most commonly consumed fruits in worldwide. In this study, catechin, chlorogenic acid and phlorizin dihydrate were purified and identified by HPLC and GC/MS. The contents of catechin, chlorogenic acid and phlorizin dihydrate were 1.01 mg, 7.01 mg and 3.67 mg/ kg wet weight, respectively. Catechin and phlorizin dihydrate were found to significantly inhibit oxidative DNA damage, while chlorogenic did not affect. Also, catechin inhibits NO and $PGE_2$ production via suppressing iNOS and COX-2 expression. However, chlorogenic acid and phlorizin dihydrate did not affect. Our results show that catechin may be the most active phenolic compound in anti-oxidative damage and anti-inflammatory effect.

UV-responsive intracellular signaling pathways: MAPK, p53, and their crosstalk

  • Matsuda, Naoki
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.229-232
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    • 2002
  • There are two distinct UV-responsive signaling pathways in UV-irradiated mammalian cells, i.e., the DNA damage-dependent and -independent pathways. The former occurs in nucleus and results in growth arrest and apoptosis via post-translational modification of p53. The latter is initiated by oxidative stress and/or by damages in cell membrane or cytoplasm, which activate signaling cascade through intracellular molecules including mitogen activated protein kinases (MAPK). In normal human fibroblastic cells, all of MAPK family members, extracellular signal-related kinases (ERK), c-Jun N-terminal kinases (JNK) and p38, were rapidly phosphorylated following UV-irradiation. ERK phosphorylation was suppressed by an inhibitor of receptor tyrosine kinases (RTK). As ERK usually responds to mitogenic stimuli from RTK ligands, UV-induced ERK phosphorylation may be linked to the proliferation of survived cells. In contrast, phosphorylation of JNK and p38, as well as apoptosis, were modulated by the level of UV-generated oxidative stress Therefore, JNK and p38 may take part in oxidative stress-mediated apoptosis. Phosphorylation of p53 at Ser and Thr residues are essential for stabilization and activation of p53. Among several sites reported, we confirmed phosphorylation at Ser-15 and Ser-392 after UV-irradiation. Both of these were inhibited by a phosphoinositide 3-kinase inhibitor, presumably due to the shutdown of signals from DNA damage to p53. Phosphorylation at Ser-392 was also sensitive to an antioxidant and a p38 inhibitor, suggesting that Ser-392 of p53 is one of the possible points where DNA damage-dependent and -independent apoptic signals merge. Thus, MAPK pathway links UV-induced intracellular signals to the nuclear responses and modifies DNA damage-dependent cellular outcome, resulting in the determination of cell death.

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Changes in Urinary MDA and 8-OHdG Concentrations due to Wearing Personal Protective Equipment and Performing Protective Behaviors among Agricultural Workers in Korea (우리나라 일부 농업 종사자의 개인보호구 착용, 작업위생행위에 따른 소변 중 MDA, 8-OHdG 농도 변화)

  • Lee, Jiyun;Ji, Kyunghee;Kim, Bokyung;Park, Seokhwan;Kim, Pan-Gyi
    • Journal of Environmental Health Sciences
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    • v.43 no.6
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    • pp.467-477
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    • 2017
  • Objectives: Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to health effects such as cancer and neurological diseases. We investigated whether protective measures could significantly reduce the levels of biomarkers for oxidative stress and DNA damage in agricultural workers. Methods: In the present study, the levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), biomarkers related to oxidative stress and DNA damage, respectively, were analyzed in urine samples collected from agricultural workers in two provinces of Korea (n=60). The influence of wearing personal protective equipment (PPE) and performing protective behaviors on the levels of these two biomarkers was also evaluated. Results: The median urinary levels of MDA and 8-OHdG were 10.45 nmol/mg creatinine and 14.42 ng/mg creatinine in subjects living in region A, while they were 6.25 nmol/mg creatinine and 24.77 ng/mg creatinine in subjects living in region B, respectively. The levels of MDA and 8-OHdG were higher in male farmers. Farmers wearing greater numbers of PPE and performing more protective behaviors had significantly lower levels of MDA. Greater numbers of protective behaviors was significantly associated with lower levels of 8-OHdG. Conclusion: The results of the present study indicate that pesticide exposure could induce oxidative stress and DNA damage in agricultural workers, and that protective measures are important for mitigating pesticide exposure.

Antioxidative Effect of Rhus javanica Linne Extract Against Hydrogen Peroxide or Menadione Induced Oxidative Stress and DNA Damage in HepG2 Cells

  • Chun, Chi-Sung;Kim, Ji-Hyun;Lim, Hyun-Ae;Sohn, Ho-Yong;Son, Kun-Ho;Kim, Young-Kyoon;Kim, Jong-Sang;Kwon, Chong-Suk
    • Preventive Nutrition and Food Science
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    • v.9 no.2
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    • pp.150-155
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    • 2004
  • The free radical scavenging activities and the protective effects of Rhus javanica extracts against oxidative damage induced by reactive oxygen species (ROS) were investigated. n-Hexane, ethyl acetate and water fractions were prepared from a methanol extract. DPPH radical, superoxide anion and hydroxyl radical scavenging activities were estimated. Intracellular ROS formation was quantified using fluorescent probes, 2', 7'-dichlorofluorescin diacetate (DCFH-DA) for hydroxyl radical and dihydroethidium (DHE) for superoxide anion. The oxidative DNA damage was investigated by the comet assay in HepG$_2$ cells exposed either to $H_2O$$_2$ or to menadione. The highest $IC_{50}$/ values for DPPH radical scavenging activity was found in the ethyl acetate fraction with a value of 5.38 $\mu\textrm{g}$/mL. Cells pretreated with $\geq$ 1 $\mu\textrm{g}$/mL of the ethyl acetate extract had significantly increased cell viability compared to control cells, which were not pretreated with the extract. Intracellular ROS formation and DNA damage in HepG$_2$ cells, which were pretreated with the various concentrations of Rhus javanica ethyl acetate extract and then incubated either with $H_2O$$_2$ or with menadione, reduced in a dose-dependent manner. These findings suggest that Rhus javanica might have biologically active components which have strong protective effects against ROS induced oxidative damages to the biomolecules, such as cell membranes and DNA.

THE EFFECT OF GENISTEIN CONCENTRATED POLYSACCHARIDE (GCP) SUPPLEMENTATION ON OXIDATIVE DNA DAMAGE AND PLASMA TOTAL ANTIOXIDANT POTENTIAL IN OLD FEMALE SPRAGUE-DAWLEY RATS.

  • Park, Eunju;Shin, Jang-In;Park, Ok-Jin;Kang, Myung-Hee
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.118-119
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    • 2001
  • The anti-cardiovascular effect of estrogen replacement therapy in postmenopausal women is known to be associated with its role as an antioxidant, its ability to protect cells from DNA damage. Genistein concentrated polysaccharide (GCP) is a functional food produced by fermentation of soybean isoflavone extracts with Basidiomycetes, containing rich content of genistein aglycones. The aim of this study was to investigate the effect of GCP on oxidative DNA damage and plasma total antioxidant potential, comparing to the effect of estrogen.(omitted)

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The Effect of Green Vegetable Drink Supplementation on Cellular DNA Damage and Antioxidant Status of Korean Smokers (녹즙혼합음료 섭취가 흡연자의 임파구 DNA 손상 및 혈장 항산화 영양상태에 미치는 영향)

  • Kim Hye-Young;Park Yoo Kyoung;Kim Tae Seok;Kang Myung-Hee
    • Journal of Nutrition and Health
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    • v.39 no.1
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    • pp.18-27
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    • 2006
  • Smoking is well known to be associated with increased indices of tree radical-mediated damage of DNA, indicating that smoking may exacerbate the initiation and propagation of oxidative stresses, which are potential underlying processes in the pathogenesis of many diseases. The purpose of this study was to evaluate whether a daily regimen of green vegetable drink supplementation to smokers can be protective against endogenous lymphocytic DNA damage and whether it could enhance other antioxidant status. Twenty nonsmokers and nineteen smokers aged 23-60 were given 240 ml of green vegetable drink every day for 8 weeks in addition to their normal diet, and blood samples were drawn before and after the intervention. The 8 weeks of green vegetable drink consumption resulted in a significant decrease (p = 0.000, by paired t-test) in lymphocyte DNA damage expressed by TL (before: $63.13{\pm}1.05$ vs after: $37.86{\pm}10.83$, before: $66.73{\pm}1.24$ vs after: $36.51{\pm}1.13$), TM (before: $14.55{\pm}0.61$ vs after: $6.61{\pm}0.25$, before: $15.36{\pm}0.45$ vs after: $6.65{\pm}0.38$) and $\%$ DNA in tail (before: $19.7{\pm}0.41$ vs after: $16.6{\pm}0.37$, before: $20.6{\pm}0.31$ vs after: $17.1{\pm}0.5$) in both nonsmokers and smokers respectively. Vitamin C and TRAP level was not significantly changed after the supplementation. In conclusion, these results support the hypothesis that green vegetable drink exert a cancer-protective effect partially via a decrease in oxidative damage to DNA.

The Growth, Innate Immunity and Protection against H2O2-Induced Oxidative Damage of a Chitosan-Coated Diet in the Olive Flounder Paralichthys olivaceus

  • Samarakoon, Kalpa W.;Cha, Seon-Heui;Lee, Ji-Hyeok;Jeon, You-Jin
    • Fisheries and Aquatic Sciences
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    • v.16 no.3
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    • pp.149-158
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    • 2013
  • We demonstrate enhanced growth, innate immunity and protection against hydrogen peroxide ($H_2O_2$)-induced protein oxidation and cellular DNA damage in olive flounder Paralichthys olivaceus fed a chitosan-coated moist pallet (MP) diet. A chitosan-based biopolymer coated MP as the experimental diet and a non-coated MP (control) was fed to olive flounder fish. Growth, including the average weight gain (g/fish), weight gain (%) and feed intake (g) of the fish group fed a chitosan-coated MP diet increased significantly. The survival rate was reported as 100% throughout the experimental period. Immunological parameters indicated higher mucus lysozyme activity and significantly higher fish skin mucus total protein content was observed in fish fed the chitosan-coated MP diet compared to the control. A blood plasma analysis revealed attenuation of cellular DNA and protein oxidative damage caused by $H_2O_2$-induced oxidative stress in the fish fed the chitosan-coated MP diet compared to the control group. Moreover, blood serum biochemical analysis revealed health-promoting effects, including significantly higher hemoglobin and total cholesterol levels in the fish fed the chitosan-coated MP diet compared to the control group. In conclusion, growth, innate immunity and protection against oxidative stresses were improved by feeding of the chitosan-coated MP diet to olive flounder reared in aquaculture.

Gender-Specific Changes of Plasma MDA, SOD, and Lymphocyte DNA Damage during High Intensity Exercise (고강도 운동 시 성별에 따른 혈장 MDA, SOD 및 임파구 DNA 손상 변화)

  • Cho, Su-Youn;Chung, Young-Soo;Kwak, Yi-Sub;Roh, Hee-Tae
    • Journal of Life Science
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    • v.21 no.6
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    • pp.838-844
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    • 2011
  • The purpose of this study was to investigate gender-specific changes of plasma MDA, SOD, and lymphocyte DNA damage during high intensity exercise. In this study, 17 healthy male and 18 healthy female college students ran on a treadmill at 85%$VO_{2max}$ until the point of all-out. Blood-collecting was carried out five times (Rest, Ex-Exha, R0.5h, R4h and R24h), and with the collected blood, plasma malondialdehyde (MDA), superoxide dismutase (SOD), and lymphocyte DNA damage were analyzed. Plasma MDA and SOD concentration increased significantly at the Ex-Exha (p<0.05), and there were no significant differences in gender. For the degree of lymphocyte DNA damage, all %DNA in the tail, tail length and tail moment increased significantly at the Ex-Exha (p<0.05), and %DNA in the tail and tail length were significantly higher in the male group than in the female group (p<0.05). These results suggest that acute high intensity exercise not only causes oxidative stress but also brings about lymphocyte DNA damage. In addition, it was found that males showed higher DNA damage than females in terms of oxidative stress subject to high intensity exercise. Nevertheless, further subsequent studies are required in order to better understand the mechanism behind DNA damage varying with gender, in a way that takes into consideration physical fitness, hormonal level, exercise intensity and duration - additional factors which might affect DNA damage.