• Title/Summary/Keyword: Oxidative damage

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Protective Effects of Samul-tang on ${H_2O_2}-induced$ Cell Apoptosis in Cultured Cardiomyoblast Cells ($H_2O_2$에 의한 배양심근세포고사에 미치는 사물탕의 방어효과)

  • 박종운;한상혁;김도환;문병순
    • The Journal of Korean Medicine
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    • v.22 no.4
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    • pp.58-68
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    • 2001
  • Objectives : This study was designed to investigate the protective mechanisms of Samul-tang (SMT) on $H_2O_2$-induced toxicity in H9c2 cardiomyoblast cells. Methods : The cultured cells were pretreated with SMT and exposed to $H_2O_2$. The cell damage was assessed by using MTT assay. Also, we used Hoechst staining, Western blotting analysis. Results : SMT significantly reduced both $H_2O_2$-induced cell death and chromatin fragmentation. The decrease of Bcl2 expression by $H_2O_2$ was inhibited by SMT. In addition, the increase of Bax expression was also inhibited by SMT. In particular, Fas expression, which is generally recognized as cell death inducing signal by Fas/FasL interaction, was markedly decreased by $H_2O_2$ in a time-dependent manner, whereas this decrease was completely prevented by SMT. The cotreatment of SMT and $H_2O_2$ in H9c2 cells also induced the phosphorylation of ERK in a time-dependent manner. Moreover, PD098059, a specific inhibitor of ERKl/2, attenuated the protective effect of SMT on $H_2O_2$-induced toxicity in H9c2 cardiomyoblast cells. Furthermore, the protective effect of SMT was significantly blocked by treatment of SB203580, a specific inhibitor of p38. Conclusions : Taken together, this study suggests that the protective effects of the water extract of SMT against oxidative damages may be mediated by the modulation of Bel2 and Bax expression via the regulation of ERK and p38 signaling pathway.

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The Relationship between Urinary 8-hydroxydeoxyguanosine and Polycyclic Aromatic Hydrocarbons Exposure in Working Environment

  • Lee Jong-Seong;Kim Eun-A;Lee Yong-Hag;Moon Deog-Hwan;Kim Kwang-Jong
    • Biomedical Science Letters
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    • v.11 no.2
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    • pp.143-152
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    • 2005
  • To investigate the exposure effect of polycyclic aromatic hydrocarbons (PAHs), we analyzed the relationship between urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration and PAHs exposure. The study population contained 44 workers in steel-pipe coating and paint manufacture industries. We measured airborne total PAHs as an external dose, urinary 1-hydroxypyrene (1-OHP) as an internal dose of PAHs exposure, and urinary 8-OHdG as an effective dose of oxidative DNA damage. There was significant correlation between the urinary concentration of l-OHP and the environmental concentration of PAHs, pyrene, urinary cotinine, AST, and GGT. The mean of urinary 8-OHdG was $17.07\pm1.706{\mu}g/g$ creatinine in workers exposed to airborne PAHs. There was significant correlation between the urinary concentration of 8-0HdG and the airborne concentration of PAHs. From the results of stepwise multiple regression analysis about 8-OHdG, significant independents was total PAHs. In this study, there were significant correlation between the urinary concentration of 8-OHdG and the airborne concentration of PAHs. The urinary 1-OHP was effective index as a biomarker of airborne PAHs in workplace. But it was influenced by non-occupational PAHs source, smoking and biomarkers of liver function test.

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NITRIC OXIDE AND DENTAL PULP (NITRIC OXIDE와 치수)

  • Kim, Young-Kyung;Kim, Sung-Kyo
    • Restorative Dentistry and Endodontics
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    • v.27 no.5
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    • pp.543-551
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    • 2002
  • Nitric oxide (NO) is a small molecule (mol. wt. 30 Da) and oxidative free radical. It is uncharged and can therefore diffuse freely within and between cells across membrane. Such characteristics make it a biologically important messenger in physiologic processes such as neurotransmission and the control of vascular tone. NO is also highly toxic and is known to acts as a mediator of cytotoxicity during host defense. NO is synthesized by nitric oxide synthase (NOS) through L-arginine/nitric oxide pathway which is a dioxygenation process. NO synthesis involves several participants, three co-substrates, five electrons, five co-factors and two prosthetic groups. Under normal condition, low levels of NO are synthesized by type I and III NOS for a short period of time and mediates many physiologic processes. Under condition of oxidant stress, high levels of NO are synthesized by type II NOS and inhibits a variety of metabolic processes and can also cause direct damage to DNA. Such interaction result in cytostasis, energy depletion and ultimately cell death. NO has the potential to interact with a variety of intercellular targets producing diverse array of metabolic effects. It is known that NO is involved in hemodynamic regulation, neurogenic inflammation, re-innervation, management of dentin hypersensitivity on teeth. Under basal condition of pulpal blood flow, NO provides constant vasodilator tone acting against sympathetic vasoconstriction. Substance P, a well known vasodilator, was reported to be mediated partly by NO, while calcitonin-gene related peptide has provided no evidence of its relation with NO. This review describes the roles of NO in dental pulp in addition to the known general roles of it.

Relative Apoptosis-inducing Potential of Homeopathic Condurango 6C and 30C in H460 Lung Cancer Cells In vitro -Apoptosis-induction by homeopathic Condurango in H460 cells-

  • Sikdar, Sourav;Saha, Santu Kumar;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.17 no.1
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    • pp.59-69
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    • 2014
  • Objectives: In homeopathy, it is claimed that more homeopathically-diluted potencies render more protective/curative effects against any disease condition. Potentized forms of Condurango are used successfully to treat digestive problems, as well as esophageal and stomach cancers. However, the comparative efficacies of Condurango 6C and 30C, one diluted below and one above Avogadro's limit (lacking original drug molecule), respectively, have not been critically analyzed for their cell-killing (apoptosis) efficacy against lung cancer cells in vitro, and signalling cascades have not been studied. Hence, the present study was undertaken. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted on H460-non-small-cell lung cancer (NSCLC) cells by using a succussed ethyl alcohol vehicle (placebo) as a control. Studies on cellular morphology, cell cycle regulation, generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential (MMP), and DNA-damage were made, and expressions of related signaling markers were studied. The observations were done in a "blinded" manner. Results: Both Condurango 6C and 30C induced apoptosis via cell cycle arrest at subG0/G1 and altered expressions of certain apoptotic markers significantly in H460 cells. The drugs induced oxidative stress through ROS elevation and MMP depolarization at 18-24 hours. These events presumably activated a caspase-3-mediated signalling cascade, as evidenced by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot and immunofluorescence studies at a late phase (48 hours) in which cells were pushed towards apoptosis. Conclusion: Condurango 30C had greater apoptotic effect than Condurango 6C as claimed in the homeopathic doctrine.

Effects of Jingansikpung-tang and Gamijingansikpung-tang Water Extract on the Cultured Spinal Sensory Neurons (진간식풍탕 및 가미진간식풍탕 추출물이 배양 척수감각신경세포에 미치는 영향)

  • Seo Young Suk;Yun Sang Hak;Yeom Seung Ryong;Lee Su kyung;Shin Byung Cheul;Kwon Young Dal;Song Yung Sun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.2
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    • pp.374-379
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    • 2003
  • To evaluate the mechanism of oxidative damage by Xanthine oxidase(XO) and hypoxanthine(HX)-induced oxygen radicals, XTT assay was carried out. Neurofilament EIA and PKC activity were measured to evaluate the protective effect of Jingansikpung-tang(JST) and Gamijingansikpung-tang(GJST) water extract on cultured spinal sensory neurons damaged by XO/HX, after the cultured mouse spinal sensory neurons were preincubated with various concentrations of JST and GJST water extract for 3 hours prior to exposure of XO/HX. The results were XO/HX decreased significantly, in proportion to concentration and exposed time, the survival rate of the cultured mouse sensory neurons on XTT assay. And in proportion to concentration and exposed time on cultured spinal sensory neurons, XO/HX showed the quantitative decrease of neurofilament by EIA, increase of PKC activity, but JST and GJST showed the neuroprotective effects against decrease of neurofilament and increase of PKC activity by XO/HX. From the above results, it is concluded that XO/HX have a neurotoxic effect on cultured spinal sensory neurons and the herbs water extract, such as JST and GJST prevent the toxicity of XO/HX effectively.

Antioxidant and Cytotoxicity Effects of Luteolin

  • Park Jin-Ny;Kang Kyoung-Ah;Zhang Rui;Piao Mei Jing;Park So-Yoon;Kim Ju-Sun;Kang Sam-Sik;Hyun Jin-Won
    • Toxicological Research
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    • v.22 no.4
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    • pp.391-395
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    • 2006
  • Flavonoids are polyphenolic compounds that are ubiquitous in plants. They have been shown to possess a variety of biological activities, such as antioxidant and anticancer. Reactive oxygen species (ROS) lead to damages of cellular molecules and it is the one of various factors to induce cancer. The one of flavonoids, Luteolin, was found to scavenge 1,1-diphenyl-2-piculhydrazyl (DPPH) radical and intracellular reactive oxygen species (ROS). Moreover luteolin showed protection on hamster lung fibroblast cells (V79-4 cell) damage induced by $H_2O_2$. And then it was investigated whether it may show cytotoxicity effect against various cancer cells by MTT, Luteolin at $10{\mu}g/ml$ showed the cell viability of 63.2%, 34.7%, 18.4% and 71.4% against NCl-H460, HeLa, U937 and MCF-7, respectively. As a result, luteolin shows more sensitive to U937 cells among the tested cancer cell lines. In summary, luteolin has antioxidant and cytotoxicity effect or various cancer cell lines.

Role of Glutathione Redox System on the T-2 Toxin Tolerance of Pheasant (Phasianus colchicus)

  • Fernye, Csaba;Ancsin, Zsolt;Bocsai, Andrea;Balogh, Krisztian;Mezes, Miklos;Erdelyi, Marta
    • Toxicological Research
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    • v.34 no.3
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    • pp.249-257
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    • 2018
  • The purpose of the present study was to evaluate the effects of different dietary concentrations of T-2 toxin on blood plasma protein content, lipid peroxidation and glutathione redox system of pheasant (Phasianus colchicus). A total of 320 one-day-old female pheasants were randomly assigned to four treatment groups fed with a diet contaminated with different concentrations of T-2 toxin (control, 4 mg/kg, 8 mg/kg and 16 mg/kg). Birds were sacrificed at early (12, 24 and 72 hr) and late (1, 2 and 3 weeks) stages of the experiment to demonstrate the effect of T-2 toxin on lipid peroxidation and glutathione redox status in different tissues. Feed refusal and impaired growth were observed with dose dependent manner. Lipid-peroxidation was not induced in the liver, while the glutathione redox system was activated partly in the liver, but primarily in the blood plasma. Glutathione peroxidase activity has changed parallel with reduced glutathione concentration in all tissues. Based on our results, pheasants seem to have higher tolerance to T-2 toxin than other avian species, and glutathione redox system might contribute in some extent to this higher tolerance, in particular against free-radical mediated oxidative damage of tissues, such as liver.

Neurotoxin-Induced Pathway Perturbation in Human Neuroblastoma SH-EP Cells

  • Do, Jin Hwan
    • Molecules and Cells
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    • v.37 no.9
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    • pp.672-684
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    • 2014
  • The exact causes of cell death in Parkinson's disease (PD) remain unknown despite extensive studies on PD.The identification of signaling and metabolic pathways involved in PD might provide insight into the molecular mechanisms underlying PD. The neurotoxin 1-methyl-4-phenylpyridinium ($MPP^+$) induces cellular changes characteristic of PD, and $MPP^+$-based models have been extensively used for PD studies. In this study, pathways that were significantly perturbed in $MPP^+$-treated human neuroblastoma SH-EP cells were identified from genome-wide gene expression data for five time points (1.5, 3, 9, 12, and 24 h) after treatment. The mitogen-activated protein kinase (MAPK) signaling pathway and endoplasmic reticulum (ER) protein processing pathway showed significant perturbation at all time points. Perturbation of each of these pathways resulted in the common outcome of upregulation of DNA-damage-inducible transcript 3 (DDIT3). Genes involved in ER protein processing pathway included ubiquitin ligase complex genes and ER-associated degradation (ERAD)-related genes. Additionally, overexpression of DDIT3 might induce oxidative stress via glutathione depletion as a result of overexpression of CHAC1. This study suggests that upregulation of DDIT3 caused by perturbation of the MAPK signaling pathway and ER protein processing pathway might play a key role in $MPP^+$-induced neuronal cell death. Moreover, the toxicity signal of $MPP^+$ resulting from mitochondrial dysfunction through inhibition of complex I of the electron transport chain might feed back to the mitochondria via ER stress. This positive feedback could contribute to amplification of the death signal induced by $MPP^+$.

Analysis of Nutritional Index of Frequently Consumed Fruits in South Korea (한국인 다빈도 섭취 과일의 영양관련 지수 분석)

  • Ryu, Ji-Hyun;Yim, Jung-Eun;Lim, Hyunjung;Choue, Ryowon
    • Journal of the Korean Society of Food Culture
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    • v.29 no.6
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    • pp.659-667
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    • 2014
  • Fruits are good sources of vitamins, minerals, fiber, and phytochemicals, which are known to reduce serum lipids, oxidative damage, and blood pressure as well as improve blood glucose control. The purpose of this study was to estimate nutrient quality indices of fruits by carrying out a critical analysis of pre-existing methods according to their nutritional compositions. Four methods were used to assess the nutrient indices of 26 fruits, which are frequently consumed by Koreans based on the fourth Korean National Health and Nutrition Examination Survey (2009). Naturally nutrient rich score (NNR), nutrient rich food (NRF), nutrient adequacy score (NAS), and nutrient density score (NDS) were used to calculate nutrient quality indices. The Korean Nutrition Society Food Composition database of fruits based on 100 g edible portions was used. The algorithm of each method included the mean percentage of daily values (Dietary Reference Intakes for Koreans, 2010) for particular nutrients based on consumption of 1,900 kcal/day. The relative score indicated that strawberries, kumquat, and lemon had high nutrient quality indices. In addition, mango, lemon, persimmon, strawberry, apricot, and tangerine fruits are rich in antioxidant nutrients such as ${\beta}$-carotene, vitamin C, vitamin E, and selenium. However, scores of nutrient quality indices did not imply that higher scores of particular fruits are superior. We suggest moderate seasonable consumption a variety of fruits. Our results can be used as a reference for consumers when they choose fruits.

The Protective Effects of Isoflavone Extracted from Soybean Paste in Free Radical Initiator Treated Rats

  • Nam, Hye-Young;Min, Sang-Gi;Shin, Ho-Chul;Kim, Hwi-Yool;Fukushima, Michihiro;Han, Kyu-Ho;Park, Woo-Jun;Choi, Kang-Duk;Lee, Chi-Ho
    • Food Science and Biotechnology
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    • v.14 no.5
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    • pp.586-592
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    • 2005
  • This study was performed to investigate the antioxidant effects of Korean soybean paste extracts (SPE) on 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced liver damage in rats. Thirty healthy Sprague Dawley rats were selected and divided into 5 groups. Isoflavone contents were measured using HPLC technique. The antioxidant activity was measured in the plasma and liver of the rats with the following results. Levels of isoflavone in fermented soy paste, red pepper paste and soy sauce were 28.9, 30.3 and $3.4\;{\mu}g/g$ for daidzein and 244.3, 187.7 and $6.1\;{\mu}g/g$ for genistein, respectively. The activities of glutamate oxaloacetic transaminase (GOT) and glutamate pyruvate transaminase (GPT) were significantly higher in the AAPH-treated group in the SPE-AAPH group (p<0.05). The thiobarbituric acid reactive substance (TBARS) production was significantly increased in the AAPH-treated liver tissue (P<0.05). Glutathione peroxidase (GPx), glutathione reductase (GR) and catalase in the liver were significantly (p<0.05) decreased by AAPH administration. The glutathione (GSH) concentration was higher in the SPE-treated (Ed- confirm) group than in the control and other groups (p<0.05). These results suggest that SPE led to increased anti oxidative activities against AAPH-induced peroxyl radical.