• Title/Summary/Keyword: DNA damages

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Protection of spontaneous and glutamate-induced neuronal damages by Soeumin Sibjeundaibo-tang and Soyangin Sibimijihwang-tang in cultured mice cerebrocortical cells

  • Lee, Mi-Young;Ma, Jin-Yeul;Choo, Young-Kug;Jung, Kyu-Yong
    • Advances in Traditional Medicine
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    • v.1 no.1
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    • pp.55-63
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    • 2000
  • Soeumin Sibjeundaibo-tang (SJDBT) and Soyangin Sibimijihwang-tang (SMJHT) have been used traditionally to improve the systemic blood circulation and biological energy production in the patients with circulatory and neuronal diseases. The object of this study is to determine the protective effects of SJDBT and SMJHT extracts on the spontaneous and glutamate-induced neuronal damages in cultured cells derived from mice cerebral cortex. At 14 days after beginning the cultures, the activity of lactate dehydrogenase released into the culture media was significantly decreased by treatment of cerebroneuronal cells with SJDBT and SMJHT (0.1 mg/ml) for 7 days. By comparison with the normal cells, cerebroneuronal morphology was dramatically changed by treatment of glutamate (1 mM) for 12 hrs, and this was conspicuously recovered by pretreatment of cerebroneural cells with SJDBT and SMJHT (0.1-1.0 mg/ml) for 2 days. Moreover, glutamated-induced DNA fragmentation was also protected by pretreatment of cerebroneuronal cells with those extracts. These results suggest that naturally occurring and glutamate-induced degeneration of cultured cerebrocortical cells may be related, in part, to the process of apoptotic cell death. The pharmacological properties of SJDBT and SMJHT extracts to improve cerebroneuronal degeneration may be considered as one of useful medicines that can prevent cerebrocortical impairments resulted from age-dependent and excitotoxicity-induced neuronal degeneration in human brain.

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Effects & Mechanism of Omija-tang on Oxidative Stress-Induced Death of H9c2 Cardiomyoblast Cell (심근세포의 산화적 손상에 대한 오미자탕의 효과 및 작용기전 연구)

  • 황보연;양경석;이상관;이기상;문병순;신선호
    • The Journal of Korean Medicine
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    • v.23 no.4
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    • pp.140-150
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    • 2002
  • Objectives: The water extract of Omija-tang (OMIT) has traditionally been used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of OMJT rescues cells from these damages. Therefore, this study was designed to investigate the protective mechanisms of OMJT on oxidative stress-induced toxicity in H9c2 cardiomyoblast cells. Methods: Treatments of $H_2O_2$, or $ZnC_{12}$ markedly induced death of H9c2 cardiomyoblast cells in a dose-dependent manner. The characteristics of oxidative stress-induced death of H9c2 showed apparent apoptotic features such as DNA fragmentation. OMJT significantly reduced both ${H_2O_2}-induced$ cell death and chromatin fragmentation. The decrease of B치-XL expression by $H_2O_2$ were inhibited by OMJT. In addition, the increase of Bcl-XS expression was also inhibited by OMJT. In particular, Fas expression, which is generally recognized as cell death-inducing signal by Fas/FasL interaction, was markedly increased by H2O2 in a time-dependent manner. Also, the expression profile of proteins in Chang cells were screened by using two-dimensional (2-D) gel electrophoresis. Among 300 spots resolved in 2-D gels; the comparison of control versus apoptotis cells revealed that signal intensity of 6 spots decreased and 11 spots increased. Results and Conclusions: Taken together, this study suggests that the protective effects of the water extract of OMJT against oxidative damages may be mediated by the modulation of Bcl-XL/S Fas expression.

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Protective Effects of Gyungokgo on Oxidative Stress-Induced Apoptosis of H9c2 Cardiomyoblast Cells (산화적 손상으로 유발된 심근세포 고사에 대한 경옥고의 방어효과)

  • Shin Sun-Ho;Yang Kyung-Suk
    • The Journal of Korean Medicine
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    • v.25 no.3
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    • pp.149-159
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    • 2004
  • Backgrounds & Objectives : The water extract of Gyungokgo (GOG) has traditionally been used for treatment of general weakness and hemoptysis in oriental medicine. However, little is known about the mechanism by which the water extract of GOG rescues cells from these damages. This study was designed to investigate the protective mechanisms of GOG on H2O2­induced cell death in H9c2 cardiomyoblasts. Methods : In this study, we used H9c2 cells. Cells were treated with oxidative stress in the absence and presence of 1000㎍/ml GOG for 12hrs. Cells were treated with various concentrations of GOG for 12hrs. Cell viability was measured by MTT assay. Oxidative stress, which markedly decreased the viability of H9c2 cells, was characterized by apparent apoptotic features such as chromatin condensation as well as fragmentation of genomic DNA and nuclei. Results : GOG significantly reduced H₂O₂-induced cell death and apoptotic characteristics. The cotreatment of GOG and H₂O₂ in H9c2 cells also induced the phosphorylation of ERKs in a time-dependent manner. Moreover, PD098059, a MEK1 (upstream activator of ERK) inhibitor attenuated the protective effect of GOG on H₂O₂-induced cytotoxicity in H9c2 cardiomyoblast cells. Conclusions : These results suggest that MEK/ERK pathways play important roles in the protective effects of GOG in H9c2 cells. Taken together, they suggest that the protective effects of the water extracts of GOG against oxidative damages may be mediated by the regulation of HO-1, Fas/FasL and Bcl-XS proteins.

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Skin Protective Effect of Methylated Marliolide through Induction of NRF2/ARE (메틸말리올라이드의 NRF2/ARE 유도를 통한 피부 세포 보호 효과)

  • Lee, June;Kim, Ki Seong;Lee, Hyun Gy;Park, Changho;Ku, Minsu;Keum, Young-Sam
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.44 no.4
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    • pp.375-379
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    • 2018
  • In the present study, we have investigated whether methylated marliolide could induce NRF2 thereby exerting anti-oxidant effects. MTT assay showed that methylated marliolide did not exhibit cytotoxicity on HaCaT cells. Methylated marliolide induced a higher ARE-dependent luciferase activation in HaCaT ARE-GFP-luciferase cells, compared with resveratrol. In addition, exposure of methylated marliolide to HaCaT cells significantly induced NRF2 and transcriptionally activated HO-1 and NQO1, both of which are target genes of NRF2. Finally, methylated marliolide protected HaCaT cells against TPA-induced oxidative damages on nucleotides and lipids. Together, results shows that methylated marliolide could suppress oxidative damages through induction of NRF2 which implies that methylated marliolide might serve as a good candidate for novel cosmetic ingredient with anti-oxidant effects.

Ameliorative effect of black ginseng extract against oxidative stress-induced cellular damages in mouse hepatocytes

  • Choudhry, Qaisra Naheed;Kim, Jun Ho;Cho, Hyung Taek;Heo, Wan;Lee, Jeong-Jun;Lee, Jin Hyup;Kim, Young Jun
    • Journal of Ginseng Research
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    • v.43 no.2
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    • pp.179-185
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    • 2019
  • Background: Oxidative stress induces the production of reactive oxygen species (ROS), which play important causative roles in various pathological conditions. Black ginseng (BG), a type of steam-processed ginseng, has drawn significant attention due to its biological activity, and is more potent than white ginseng (WG) or red ginseng (RG). Methods: We evaluated the protective effects of BG extract (BGE) against oxidative stress-induced cellular damage, in comparison with WG extract (WGE) and RG extract (RGE) in a cell culture model. Ethanolic extracts of WG, RG, and BG were used to evaluate ginsenoside profiles, total polyphenols, flavonoid contents, and antioxidant activity. Using AML-12 cells treated with $H_2O_2$, the protective effects of WGE, RGE, and BGE on cellular redox status, DNA, protein, lipid damage, and apoptosis levels were investigated. Results: BGE exhibited significantly enhanced antioxidant potential, as well as total flavonoid and polyphenol contents. ATP levels were significantly higher in BGE-treated cells than in control; ROS generation and glutathione disulfide levels were lower but glutathione (GSH) and NADPH levels were higher in BGE-treated cells than in other groups. Pretreatment with BGE inhibited apoptosis and therefore protected cells from oxidative stress-induced cellular damage, probably through ROS scavenging. Conclusion: Collectively, our results demonstrate that BGE protects AML-12 cells from oxidative stress-induced cellular damages more effectively than WGE or RGE, through ROS scavenging, maintenance of redox status, and activation of the antioxidant defense system.

Effect of NaCl Treatment and Gamma Ray Irradiation on the Induction Pink Mutations in Hairs of Tradescantia Stamen (NaCl 처리와 감마선조사가 자주달개비 수술털 세포의 분홍돌연변이 유기에 미치는 영향)

  • Kim, Jin-Kyu;Kim, Won-Rok;Kim, Jae-Sung;Kim, Ki-Nam;Hong, Kwang-Phyo
    • Korean Journal of Environmental Agriculture
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    • v.18 no.1
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    • pp.41-47
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    • 1999
  • To investigate the combined effect of gamma ray irradiation and NaCl treatment on Tradescantia somatic cell pink mutations, potted plants of Tradescantia 4430 were evenly sprayed with NaCl solution(170mM) 24 hours before irradiation(NaCl+${\gamma}$) and after irradiation(${\gamma}$+NaCl). Irradiation doses were 0.3, 0.5, 1.0 and 2.0 Gy of gamma-ray. The plants irradiated only with gamma radiation were used as control group(CT). Frequency of pink mutation increased linearly with irradiation close and the peak interval of elevated mutation frequencies appeared during 6∼12 days aver irradiation in all the experimental groups. The slope of dose-response curve in CT was 5.99($r^2$=0.99), while it were 4.55($r^2$=0.98) in NaCl+${\gamma}$ and 4.33($r^2$=0.99) in ${\gamma}$+NaCl. It seemed that pre- and post-treatment of NaCl had a protective effect it against radiation-induced cell damages since it decreased the slope value by more than 24%. It is suggested that protective effect on DNA damages can be invoked in irradiated stamen hair cells by NaCl treatment.

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Importance of Oxidative Stress in Ocular Dysfunction (안구의 기능이상에 대한 산화스트레스의 중요성)

  • Lee, Ji Young
    • Journal of Korean Ophthalmic Optics Society
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    • v.13 no.3
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    • pp.103-109
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    • 2008
  • Purpose: This review illustrates an importance of oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation in association with eye disease, especially of cataract, and discusses an important role of lipid peroxide as a mediator of oxidative stress-related ocular dysfunction. Methods: Oxidative stress, resulted from the cellular production of ROS and RNS, is known to cause various forms of cellular damages such as protein oxidation, DNA breaks, apoptosis, and lipid peroxidation. These damages can be developed to human diseases. Accumulating evidence strongly suggests that continuous or constant exposure of eye tissues to oxidative stress is a main cause of cataractogenesis. Therefore, we investigated the action of oxidative stress in ocular dysfunction. Results: The ocular lens is continuously attacked by ROS inevitable generated from the process of cellular metabolism and the chronic exposure to ultraviolet. Excessive generation of ROS, resulting in degradation, oxidation, crosslinking and aggregation of lens proteins, is regarded as an important factor in development of cataract. Conclusions: These oxidative stress and oxidant/antioxidant imbalance produces the excess ROS which can lead to eye dysfunction. Even though known results, it should be noted that there is limited information on the molecular mechanism which can be better defined with the interrelation of oxidative stress and optic abnormalities.

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DNA damages with Fpg/Endo Ⅲ FLARE Assay in cynomolgus monkeys exposed to stainless steel welding fume (용접흄 흡입노출 영장류에서 Fpg/Endo Ⅲ FLARE Assay를 이용한 DNA 손상 및 회복)

  • Rim, Kyung Taek;Kim, Soo Jin;Chung, Yong Hyun;Kim, Hyeon Yeong;Maeng, Seung Hee;Yu, Il Je
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.17 no.4
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    • pp.272-281
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    • 2007
  • 선박제조업을 비롯한 운송업 및 건축업 등의 다양한 분야에서 용접기술이 이용되어 옴에 따라 용접근로자들에 대한 산업보건학적 관심이 높아지고 있다. 노출정도가 다양하기는 하지만 용접흄은 6가 크롬을 비롯한 금속화합물과 유해가스, 화학물질 등을 복합적으로 포함하고 있는 스테인레스 스틸 용접흄에 대한 유전독성영향을 평가하기 위하여 흡입챔버를 이용, 실험동물인 영장류에 스테인레스 스틸 용접흄을 노출시키고 혈액 내 lymphocytes에 생성된 용접흄 노출농도 및 시간별 DNA 손상정도 및 그 회복효소를 측정함으로써, 유해성이 완전하게 확인되지 않은 용접흄에 노출되어 나타날 수 있는 암을 비롯한 심각한 건강영향을 예방하기 위한 각 지표들을 찾아 그 유용성을 비교하고자 하였다. 영장류를 노출시키기 위해 robotic arm을 장치한 영장류 흡입노출 시스템을 개발하였으며, 이 노출 시스템을 이용하여 수컷 영장류 6마리에 대해 용접흄 노출시험을 실시하였는데 실험군은 대조군 2, 저농도 ($31mg/m^3$) 노출군 2, 고농도 ($63mg/m^3$) 노출군 2마리로 구성하였고, 1일 2시간씩 일주일에 5일 동안 용접흄에 노출시켰다. 노출 농도는 지속적으로 모니터링 하였고, 노출과정 중에 영장류의 혈액을 채취하여 lymphocytes를 분리, 단세포 DNA 손상을 선별하기 위해 DNA 손상회복 효소인 E. coli formamidopyrimidine-DNA glycosylase (Fpg)와 endonuclease Ⅲ (Thymine Glycol-DNA glycosylase) 투여와 Comet asaay (single cell gel electrophoresis, 단세포겔전기영동기법)를 결합시켜 이용하는 Fpg/Endo III FLARE 분석법을 사용하였다. Fpg enzyme에 의한 olive tail moment값의 변화는 16주 노출군부터 노출부검(34주)군 까지 노출농도가 높아짐에 따른 olive tail moment 기하평균 값의 양 반응관계를 보기는 어렵지만, 고농도군의 경우 27주 노출군에서 가장 높은 olive tail moment 값을 보이고 이후 차츰 감소하였다. 한편 16주에서 22주까지의 노출기간에서는 대조군에 비해 노출군에서 DNA손상정도(olive tail moment값)는 모두 유의하게 높았으나, 6, 12, 18, 25, 31, 33, 35주간 노출하였을 때는 다른 결과를 보였다. 각 실험군의 Fpg enzyme에 의한 tail length값의 분포를 살펴볼 때, 저농도군 및 고농도군에서 27주간 노출하였을 때 가장 높은 tail length 값을 보이고 이후 차츰 감소하는 경향을 보였다. 또한 16, 22주간 노출하였을 때 대조군에 비해 노출군에서 tail length 값이 유의하게 높았으나, 20주간에서만 양 반응관계가 관찰되었고, 다른 주간에서는 양 반응 및 기간 반응관계를 나타내지는 않았다. Endo III enzyme에 의한 olive tail moment값의 변화는 기간별 노출군에서 대조군에 비해 높은 DNA손상정도(olive tail moment값)를 나타내는 결과들이 있었지만, 10, 12, 16, 22, 25, 31주간 노출하였을 때 등 상당수 노출기간에서 반응관계를 나타내지는 않았다. 각 실험군의 Endo III enzyme에 의한 tail length값의 분포를 살펴볼 때, 18, 20, 27, 33주간 노출하였을 때 대조군에 비해 노출군에서 tail length 값이 조금 높았지만, 양 반응 및 기간 반응관계를 보이지 않았고 수치의 크기가 불규칙하게 변화하였다. 즉, DNA에 있어 산화된 pyrimidine을 형성하여 손상된 부위의 염기를 제거함으로써 AP site (abasic site)를 만들고 이들이 Comet assay를 통해 break로 전환된 것을 포함한 DNA손상을 측정하기 위하여 endonuclease III (Endo III)를 첨가시킨 Endo III FLARE 분석법을 실시한 결과, 본 연구에서 나타난 결과는 용접흄 노출 영장류에서 Olive tail moment 및 tail length 공히 노출량 및 노출기간 반응관계를 볼 수 없었다. Endo III FLARE 분석법을 통한 산화적 DNA 손상지표는 영장류에 적용하기에는 적응반응현상으로 대조군과 유의한 차이도 관찰할 수 없었고 더욱이 역으로 대조군에서의 자연발생적 수치가 더 높아질 수 있어 용접흄 노출 영장류의 모니터링 지표로 사용하기에는 제한점이 있었다.

The Development of Tobacco Litigation in USA and it's Impact of Law and Politics in Public Health (미국 담배소송의 변천과 보건법정책 효과)

  • Kim, Un-Mook;Kim, Ji-Hyun
    • The Korean Society of Law and Medicine
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    • v.12 no.1
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    • pp.133-173
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    • 2011
  • Since mid-1960s the reports from the Surgeon General, the World Health Organization, and other health experts state that there is no risk-free level exposure to smoking and secondhand smoke. Tobacco smoke is made up of more than 7,000 chemicals. Hundreds are toxic, and at least 70 are carcinogens. The chemicals in tobacco smoke reach smoker's lungs quickly every time smoker inhale causing damages immediately. Inhaling even the smallest amount of tobacco smoke can also damage smoker's DNA, which can lead to cancers. Smoking is responsible for more than 87% of lung cancers, but there are a host of other chronic diseases directly related to exposure to tobacco smoke. It's also a major cause of heart disease, stroke, aortic aneurysm, peripheral arterial disease and most of the other diseases. In the United States, each year with more than from 440,000 to 520,000 deaths caused by smoking and exposure to involuntary smoke. They conclude that smoking is the single most important source of preventable morbidity and mortality. The United States of America have about 60-year history of tobacco litigation. Tobacco litigation has been an important tool in tobacco control strategies aimed at limiting the activities of tobacco companies and providing redress to people who have become ill as a result of their use of tobacco products. Tobacco litigation is a kind of tort litigation. Quite often, as in the asbestos and other mass tort litigation episodes, tobacco litigation can play an educational role, warning the public about the magnitude of health risks that might otherwise be less clearly perceived. Tobacco litigation allows smokers, their families or other victims of smoking to sue tobacco companies in order to be compensated for the harm they have suffered. Potential benefits of tobacco litigation include compensation for smoking-related damages, strengthening regulatory activity, publicity, documents disclosure and changing tobacco industry behavior. And also tobacco litigation can limit the political activities of tobacco industry, protect human rights of smokers and non-smokers, increase burden to tobacco price-up and enhance the effects of law and politics in public health.

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Antimutagenic Activities of the Germinated Specialty Rices in E. coli and V79 Cultured Cell Assay Systems (E. coli와 V79 배양세포계에서 발아특수미의 항돌연변이 활성)

  • Kang, Mi-Young;Nam, Seok-Hyun
    • Applied Biological Chemistry
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    • v.48 no.3
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    • pp.222-227
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    • 2005
  • To evaluate the antimutagenic activity of the specialty rices, a giant embryonic rice and a pigmented rice, we measured the inhibitory effect on the chemically induced mutagenesis in E. coli and V79 cultured cell system, as well as on DNA strand scission induced by oxidative damages in vitro. When the inhibitory activity to mitomycin C-induced mutagenesis using SOS chromotest in E. coli cell was measured, the activities decreased in the following order: germinated pigmented rice (40.4%) > germinated giant embryonic rice (37.1%) > pigmented rice (35.5%) > germinated brown rice (15.7%) > giant embryonic rice (14.0%) > brown rice (0.8%). The activities for inhibiting mitomycin C-induced DNA strand scission decreased in the order of pigmented rice > giant embryonic rice > germinated pigmented rice > germinated brown rice > brown rice > germinated giant embryonic rice. We also determined antimutagenic activities of the specialty rices using the suppressing effect on 6-TG resistant colony formation by 4-NQO in V79 cells as a mutagenicity index. The order of antimutagenicity was germinated giant embryonic rice (53.2%) > pigmented rice (40.0%) > brown rice (21.2%) > germinated brown rice (14.4%) > giant embryonic rice (0.23%); in contrast, germinated pigmented rice showed promoting effect on 4-NQO-induced mutagenesis.