• Journal of Nutrition and Health
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• 제29권7호
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• pp.721-728
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• 1996

The level of oxidative tissue damage caused by free radicals generated from ethanol oxidation was determined in the myocardium of chronic ethanol fed-rats and the protective action of various radical scavenging enzymes was monitored, also. Adult male Sprague-Dawley rats were given ethanol in an amount of 36% of total calories via Lieber-DeCarli liquid diet for 6 weeks. Control group was pair-fed with the diet containing isocaloric amount of dextrin-maltose instead of ethanol. Chronic ethanol administration resulted in the increased amount of myocardial thiobarbituric acid reactive substance(TBARS), th parameter of lipid peroxidation, under our experimental condition. Chronic ethanol ingestion did not cause any change in activities of either glutathione peroxidase or glutathione reductase and glucose-6-phosphate dehydrogenase were decreased after ethanol treatment. Therefore, chronic ethanol administration seemed to cause considerble changes in cellular defense function against oxidative tissue damage in rat myocardium through glutathione utilizing system and radical generation system. However the ultimate net result of chronic ethanol inestion on the myocardium of rat was the oxidative tissue damage revealed by increased TBARS content.

• 대한의생명과학회지
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• 제11권2호
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• pp.103-108
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• 2005

2-Deoxyribonolactone (dL) arises as a major DNA damage induced by a variety of agents, involving free radical attack and oxidation of C1'-deoxyribose in DNA. We investigated whether dL lesions can be repaired in mammalian cells and the mechanisms underlying the role of DNA polymerase $\beta$ in processing of dL lesions. Pol $\beta$ appeared to be trapped by dL residues, resulting in stable DNA-protein cross-links. However, repair DNA synthesis at site-specific dL sites occurred effectively in cell-free extracts, but predominantly accompanied by long-patch base excision repair (BER) pathway. Reconstitution of long-patch BER demonstrated that FEN1 was capable of removing the displaced flap DNA containing a 5'-dL residue. Cellular repair of dL lesions was largely dependent on the DNA polymerase activity of Pol $\beta$. Our observations reveal repair mechanisms of dL and define how mammalian cells prevent cytotoxic effects of oxidative DNA lesions that may threaten the genetic integrity of DNA.

• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.246-253
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• 2007

Doxorubicin and daunorubicin are excellent chemotherapeutic agents utilized for several types of cancer but the irreversible cardiac damage is the major limitation for its use. The biochemical mechanisms of doxorubicin- and daunorubicin- induced cardiotoxicity remain unclear. There are many reports on toxicity of doxorubicin and doxorubicin in cardiomyocytes, but effects in cardiovascular system by these drugs are almost not reported. In this study, we investigated gene expression profiles in human umbilical vein endothelial cells (HUVECs) to better understand the causes of doxorubicin and doxorubicininduced cardiovascular toxicity and to identify differentially expressed genes (DEGs). Through the clustering analysis of gene expression profiles, we identified 124 up-regulated common genes and 298 down-regulated common genes changed by more than 1.5-fold by all two cardiac toxicants. HUVECs responded to doxorubicin and doxorubicin damage by increasing levels of apoptosis, oxidative stress, EGF and lipid metabolism related genes. By clustering analysis, we identified some genes as potential markers on apoptosis effects of doxorubicin and doxorubicin. Six genes of these, BBC3, APLP1, FAS, TP53INP, BIRC5 and DAPK were the most significantly affected by doxorubicin and doxorubicin. Thus, this study suggests that these differentially expressed genes may play an important role in the cardiovascular toxic effects and have significant potential as novel biomarkers to doxorubicin and doxorubicin exposure.

• Molecular & Cellular Toxicology
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• 제1권2호
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• pp.111-115
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• 2005

Ultraviolet (UV) radiation to mammalian skin is known to alter cellular function via generation of Reactive Oxygen Species (ROS), DNA damage and DNA lesions, such as pyrimidine dimmers and photoproducts, which could lead to DNA mutation if they are not repaired. In this study, we have investigated the reduction of DNA damage and of apoptosis with a particular attention to genetic effect of paeoniflorin in Normal Human Epidermal Keratinocytes (NHEK). After UVB irradiation from $10\;to\;500mJ/cm^{2}$ to NHEK, Mean Tail Moments (MTM) were increased with UVB dose increase. The greatest amount of strand breaks was induced at $500mJ/cm^{2}$ of UVB. Even at the lowest dose of UVB ($10mJ/cm^{2}$), change in MTM was detected (P<0.0001). Pretreated cell with 0.1% paeoniflorin maximally reduced the level of DNA damage to about 21.3%, compared to untreated cell. In the lower concentrations less than 0.01% of paeoniflorin, MTM had a small increase but paeoniflorin still had reductive effects of DNA damage. We measured the apoptosis suppression of paeoniflorin with annexin V flous staining kit. As we observed under the fluorescence microscopy to detect apoptosis in the irradiated cell, the fluorescence intensity was clearly increased in the untreated cell, but decreased in treated cells with paeoniflorin. These results suggest that paeoniflorin reduces the alteration of cell membranes and prevents DNA damage. Therefore, the use of paeoniflorin as a free radical scavenger to reduce the harmful effects of UV lights such as chronic skin damage, wrinkling and skin cancer can be useful to prevent the formation of photooxidants that result in radical damage.

• Molecules and Cells
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• 제40권9호
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• pp.607-612
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• 2017

When mammalian cells and animals face a variety of internal or external stresses, they need to make homeostatic changes so as to cope with various stresses. To this end, mammalian cells are equipped with two critical stress responses, autophagy and cellular senescence. Autophagy and cellular senescence share a number of stimuli including telomere shortening, DNA damage, oncogenic stress and oxidative stress, suggesting their intimate relationship. Autophagy is originally thought to suppress cellular senescence by removing damaged macromolecules or organelles, yet recent studies also indicated that autophagy promotes cellular senescence by facilitating the synthesis of senescence-associated secretory proteins. These seemingly opposite roles of autophagy may reflect a complex picture of autophagic regulation on cellular senescence, including different types of autophagy or a unique spatiotemporal activation of autophagy. Thus, a better understanding of autophagy process will lead us to not only elucidate the conundrum how autophagy plays dual roles in the regulation of cellular senescence but also helps the development of new therapeutic strategies for many human diseases associated with cellular senescence. We address the pro-senescence and anti-senescence roles of autophagy while focusing on the potential mechanistic aspects of this complex relationship between autophagy and cellular senescence.

• 약학회지
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• 제43권6호
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• pp.851-860
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• 1999

The effects of antimycin A(AA), dodium azide ($NaN_3$) and 2,4-dinitrophenol (DNP), which inhibit mitochondrial ATP production, on cellular functions of cultured astrocytes were studied. High concentrations of AA $(50{\;}\mu\textrm{g}/ml),{\;}NaN_3$ (100mM) and DNP (20mM) significantly decreased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction, which was known to be related to mitochondrial function and then cel viability. AA ($50{\;}\mu\textrm{g}/ml$) increased lactate dehydrogenase (LDH) release and decreased [$^3H$] glutamate uptake, suggesting severe damage of cellular function by the concentrations of the compounds. Meanwhile, low concentrations of AA $(\leq{;\}10{\;}\mu\textrm{g}/ml),{\;}NaN_3{;\}(\leq{\;}50mM)$ and DNP ($\leq{\;}5mM$) significantly increased MTT reduction, the effect of which was specific to astrocytes. AA (5 and $10{\;}\mu\textrm{g}/ml$) did not affect LDH release and [$^3H$] glutamate uptake, indicating that these compounds increased MTT reduction at the low concentrations without cellular membrane damage. However, the low concentrations of AA produced significant decrease of MTT reduction in a glucose-free medium. Low concentrations of AA (1 and $5{\;}\mu\textrm{g}/ml$) did not change ATP production of astrocytes in the medium containing 10 mM glucose, but completely inhibited in a glucose-free medium, suggesting marked increase of cytosolic ATP production by the blockade of mitochondrial ATP production with low concentrations of AA. These results suggest that astrocytes have ability to enhance neuronal function or survival under conditions of incomplete ischemia or early by enhancement of glycolysis, and that cellular reduction of MTT occurs not only mitochondrially but also extramitchondrially.

• Journal of Nutrition and Health
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• 제36권1호
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• pp.24-31
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• 2003

The present study was attempted to investigate the antioxidant capacity of popular yellow-green vegetable juices (kale, Angelica keishei, carrot, small water dropwort) and to investigate the effect of vegetable juices on protecting oxidative damage to DNA in cultured Chinese hamster lung (CHL) cells. Antioxidant capacity was analyzed by TRAP assay (Total radical-trapping antioxidant potential). Cellular DNA dmamage was measured by SCGE (single-cell gel electrophoresis, also known as comet assay. Cells incubated in medium with PBS (negative control) or with various concentration of the freeze dried green juices (25, 50, 100, 250 $\mu\textrm{g}$/$m\ell$) resuspended in PBS were treated with $H_2O_2$ (200 ${\mu}{\textrm}{m}$) as an oxidative stimulus for 5 min at 4$^{\circ}C$. The physiological function of each vegetable juice on oxidative DNA damage was analyzed and expressed as tail moment (tail length X percentage migrated DNA in tail) . Kale juice had the highest TRAP value suggesting that kale has the highest antioxidant capacity followed by Angelica keishei, small water dropwort and carrot. Cells treated with $H_2O_2$ had extensive DNA damage compared with cells treated with PBS or pre-treated with vegetable juice extracts. All green juices inhibited $H_2O_2$-induced DNA damage with kale being the most effective juice among the tested juices. These results indicate that green juice supplementation to CHL cells followed by oxidative stimulus inhibited damage to cellular DNA, supporting a protective effect against oxidative damage induced by reactive oxygen species. (Korean J Nutrition 36(1) : 24-31, 2003)

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.291-312
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• 2003

Reactive oxygen species are capable of damaging biomolecules such as lipids, proteins, and DNA, which can not only lead to various diseases, but also oxidative damage resulting aging. In our previous study, Cercis chinensis (Leguminosae) showed a potent antioxidant activity. Nineteen compounds were isolated through antioxidant activity-guided fractionation. The C. chinensis extract and some of the constituents exhibited a potent antioxidant activity on the free radicals and lipid peroxidation and a notable protective effect on the t-BuOOH induced oxidative damage. In vivo test of skin damage induced by UVB irradiation, the extract of C. chinensis and a constituent, piceatannol, exhibited a significant protective effect. The life-span of the HEK-N/F cells were extended by 1.21-2.12 fold as a result of the continuous administration of 3 $\mu\textrm{g}$/ml of the C. chinensis extract and the active constituents compared to that of the control. These observations were attributed to the inhibitory effect of the C. chinensis extract and its constituents on the age-dependent shortening of the telomere. Thus, C. chinensis was demonstrated to protect the skin cells against oxidative stress and inhibit thereby the cellular aging, followed by expectation as anti-aging cosmetic ingredient.

• 한국한의학연구원논문집
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• 제3권1호
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• pp.229-239
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• 1997

The superoxide anion radical$(O_2)$ poses a threat to macromocules and cell organelles of the living cells. This toxicity damage to all groups of proteins results in loss of enzyme function concerned with metabolism and ion transport, and peroxidation of unsaturated fatty acids and cholesterol results in a change of permeability characteristics of the membrane, and oxidative of nucleic acids results in genomic damage and thereby cause mutation, potential carcinogenesis and somatic damage that produce cellular aging Superoxide dismutase(SOD) has received substantial attention as a potential therapeutic agent. It has been investigated as a possible agent for the prevention of ontogenesis, the reduction of cytotoxic effect of anticancer drugs, and protection against damage in ischemic tissue. It is suggest that $O_2$ is concerned with cellular aging, thereafter we need to investigate herb that activated to SOD.

• Toxicological Research
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• 제23권3호
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• pp.207-214
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• 2007

Chronic oxidative stress produced by exposure to environmental chemicals or pathophysiological states can lead animals to aging, carcinogenesis and degenerative diseases. Indirect antioxidative mechanisms, in which natural or synthetic agents are used to coordinately induce the expression of cellular antioxidant capacity, have been shown to protect cells and organisms from oxidative damages. Electrophile and free radical detoxifying enzymes, which were originally identified as the products of genes induced by cancer chemopreventive agents, are members of this protective system. The NFE2 family transcription factor Nrf2 was found to govern expression of these detoxifying enzymes, and screening for Nrf2-regulated genes has identified many gene categories involved in maintaining cellular redox potential and protection from oxidative damage as Nrf2 downstream genes. Further, studies using Nrf2-deficient mice revealed that these mutant mice showed more susceptible phenotypes towards exposure to environmental chemicals/carcinogens and in oxidative stress related disease models. With the finding that cancer chemopreventive efficacy of indirect antioxidants (enzyme inducers) is lost in the absence of Nrf2, a central role of Nrf2 in the antioxidative protective system has been firmly established. Promising results from cancer prevention clinical trials using enzyme inducers propose that pharmacological interventions that modulate Nrf2 can be an effective strategy to protect tissues from oxidative damage.