National Institute of Toxicological Research

Seoul, South Korea

National Institute of Toxicological Research

Seoul, South Korea
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Thuong P.T.,Vietnam National University, Hanoi | Hung T.M.,Catholic University of Daegu | Ngoc T.M.,Chungnam National University | Ha D.T.,Chungnam National University | And 5 more authors.
Phytotherapy Research | Year: 2010

The aim of this work was to study the structure-activity relationships of the antioxidant activity of natural coumarins isolated from four Korean medicinal plants (1-17) and four purchased coumarins (18-21). The free radical scavenging and lipid peroxidation assays revealed that five phenolic coumarins, scopoletin (1), aesculetin (2), fraxetin (3), umbelliferone (18) and daphnetin (19), possessed considerable antioxidant activities. The coumarins having a catechol group, 2, 3 and 19, showed significant free radical scavenging activity and inhibitory effects on lipid peroxidation, indicating that the catechol group significantly contributed to the antioxidant activities of coumarins. In contrast, the sugar moiety markedly reduced the activities of coumarin glycosides. The results also demonstrate that the α-pyrone ring of coumarins significantly enhanced the capacity of inhibiting oxidative reactions of coumarins. Copyright © 2009 John Wiley & Sons, Ltd.

Park Y.-H.,Laboratory of Cell Signaling and Nanomedicine | Kim J.N.,Laboratory of Cell Signaling and Nanomedicine | Jeong S.H.,Laboratory of Cell Signaling and Nanomedicine | Choi J.E.,Laboratory of Cell Signaling and Nanomedicine | And 7 more authors.
Toxicology | Year: 2010

Assessments of skin irritation potentials are important aspects of the development of nanotechnology. Nanosilica is currently being widely used for commercial purposes, but little literature is available on its skin toxicity and irritation potential. This study was designed to determine whether nanosilica has the potential to cause acute cutaneous toxicity, using cultured HaCaT keratinocytes (CHK), a human skin equivalent model (HSEM), and in vivo model. Nanosilica was characterized by scanning electron microscopy. We evaluated the cytotoxic effects of nanosilica on CHKs and the HSEM. In addition, we also investigated whether two commercially available nanosilicas with different sizes (7 and 10-20 nm) have different effects. To confirm in vitro results, we evaluated the irritation potentials of nanosilicas on rabbit skin. Nanosilicas reduced the cell viabilities of CHKs in a dose-dependent manner. However, the HSEM revealed no irritation at 500 μg/ml of nanosilica. Furthermore, this result concurred with Draize skin irritation test findings. The present study data indicate that nanosilica does not cause acute cutaneous irritation. Furthermore, this study shows that the HSEM used provides more useful screening data than the conventional cell culture model on the relative toxicities of NPs. © 2009 Elsevier Ireland Ltd. All rights reserved.

Jeong S.H.,Laboratory of Cell Signaling and Nanomedicine | Kim J.H.,Laboratory of Cell Signaling and Nanomedicine | Yi S.M.,Laboratory of Cell Signaling and Nanomedicine | Lee J.P.,National Institute of Toxicological Research | And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2010

Quantum dots (QDs) are rapidly emerging as an important class of nanoparticles (NPs) with potential applications in medicine. However, little is known about penetration of QDs through human skin. This study investigated skin penetration of QDs in both in vivo and in vitro human skin. Using the tape stripping method, this study demonstrates for the first time that QDs can actually penetrate through the stratum corneum (SC) of human skin. Transmission electron microscope (TEM) and energy diverse X-ray (EDX) analysis showed accumulation of QDs in the SC of a human skin equivalent model (HSEM) after dermal exposure to QDs. These findings suggest possible transdermal absorption of QDs after dermal exposure over a relatively long period of time. © 2010 Elsevier Inc. All rights reserved.

Choi B.-S.,Chung - Ang University | Choi S.-J.,Chung - Ang University | Kim D.-W.,Chung - Ang University | Huang M.,Chung - Ang University | And 9 more authors.
Archives of Environmental Contamination and Toxicology | Year: 2010

Arsenic (As) is a known human carcinogen and widely distributed in the environment. The main route of As exposure in the general population is through food and drinking water. Seafood harvested in Korea contains high-level organoarsenics such as arsenobetaine, arsenocholine, and arsenosugars, which are much less harmful than inorganic arsenics. However, for those who eat large amounts of seafood it is important to understand whether seafood consumption affects urinary levels of inorganic As metabolites such as arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). In this study we investigated urinary As metabolites (inorganic As, MMA[V], DMA[V]) and some biological indexes such as AST, GSH, GPX, lipid peroxidation, and uric acid in volunteer study subjects (seven males and nine females). Total urinary As metabolites were analyzed by the hydride generation method, followed by arsenic speciation using HPLC with ICP-mass spectrometry. Study subjects refrained from eating seafood for 3 days prior to the first urine collection and then ingested seafood daily for 6 consecutive days. The first voided urine of the morning was collected from each subject the first day of the consecutive 6 days of seafood ingestion but prior to the first seafood meal. The first voided urine of the morning was also collected on days 1, 2, 3, 4, 5, 6, 7, 10, and 14 after seafood ingestion. The daily mean intake of total As was 6.98 mg, comprised of 4.71 mg of seaweed (67%), 1.74 mg of flat fish (25%), and 0.53 mg of conch (8%). We observed a substantial increase in total urinary As metabolites for subjects consuming seafood from day 1, which recovered to control level at day 10. The increase in total urinary As metabolites was attributed to the increase in DMA, which is a more harmful metabolite than organoarsenics. However, no significant changes in response biological indexes were observed. These results suggest that it is necessary to evaluate As metabolism when assessing the exposure to inorganic As and potential chronic health effects of seafood consumption in Korea. © 2009 Springer Science+Business Media, LLC.

Shin B.S.,Catholic University of Daegu | Hwang S.W.,Sungkyunkwan University | Bulitta J.B.,State University of New York at Buffalo | Lee J.B.,Sungkyunkwan University | And 6 more authors.
Journal of Toxicology and Environmental Health - Part A: Current Issues | Year: 2010

The objective of this study was to predict the exposure to bisphenol A (BPA) after oral intake in human blood and tissues using physiologically based pharmacokinetic (PBPK) modeling. A refined PBPK model was developed taking into account of glucuronidation, biliary excretion, and slow absorption of BPA in order to describe the second peak of BPA observed following oral intake. This developed model adequately described the second peak and BPA concentrations in blood and various tissues in rats after oral administration. A prospective validation study in rats additionally supported the proposed model. For extrapolation to humans, a daily oral BPA dose of 0.237 mg/70 kg/d or 0.0034 mg/kg/d was predicted to achieve an average steady-state blood concentration of 0.0055 ng/ml (median blood BPA concentration in Korean pregnant women). This dose was lower than the reference dose (RfD, 0.016 mg/kg/d) and the tolerable daily intake established by the European Commission (10 μg/kg/d). Data indicate that enterohepatic recirculation may be toxicologically important as this pathway may increase exposure and terminal half-life of BPA in humans. Copyright © Taylor & Francis Group, LLC.

Hung T.M.,Catholic University of Daegu | Van Thu C.,Hanoi University of Pharmacy | Cuong T.D.,Catholic University of Daegu | Hung N.P.,Chosun University | And 6 more authors.
Journal of Natural Products | Year: 2010

Two new dammarane-type glycosides, 2α,3β,12β,20S- tetrahydroxydammar-24-ene-3-O-[β-D-glucopyranosyl(1→'4) -sβ-D-glucopyranosyl]-20-O-[β-D-xylopyranosyl-(1→6) -β-D-glucopyranoside] (1) and 2α,3β,12β,20S- tetrahydroxydammar24-ene-3-O-β-D-glucopyranosyl-20-O-[β-D-6-O- acetylglucopyranosyl-(l-→2)-β-D-glucopyranoside] (2), were isolated from a MeOH extract of the leaves of Gynostemma pentaphyllum. Their structures were elucidated by 1D and 2D NMR spectroscopic interpretation as well as by chemical studies. The isolated compounds showed potential inhibitory effects on eotaxin expression in BEAS-2B bronchial epithelial cells. © 2010 American Chemical Society and American Society of Pharmacognosy.

Kim J.S.,Seoul National University | Kim J.-M.,Seoul National University | O J.-J.,National Institute of Toxicological Research | Jeon B.S.,Seoul National University
Journal of Clinical Neuroscience | Year: 2010

The aim of this study was to investigate the involvement of inducible nitric oxide synthase (iNOS) in the action of (-)-epigallocatechin-3-gallate (EGCG), a potential neuroprotective agent against Parkinson's disease (PD), and to test for toxicity resulting from high doses of EGCG. EGCG was administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice at two different doses (10 mg/kg and 50 mg/kg). EGCG treatment reduced the neuronal death rate to less than 50%. The level of iNOS expression in the MPTP group was 20% higher than that seen in the control group, but in the EGCG groups, iNOS expression was reduced to the level observed in the negative control group. The two doses of EGCG were equally beneficial for cell rescue, and no toxicity was observed with the higher dose. Inhibition of iNOS may be an important mechanism underlying the prevention of MPTP toxicity, and EGCG may potentially be a neuroprotective agent against PD. © 2010 Elsevier Ltd. All rights reserved.

Park E.-J.,Dongduk Women's University | Cho W.-S.,National Institute of Toxicological Research | Jeong J.,National Institute of Toxicological Research | Yi J.-H.,Seoul National University | And 3 more authors.
Journal of Health Science | Year: 2010

Cerium oxide nanoparticles have a high thermodynamic affinity for oxygen and sulfur, which makes them useful in applications such as catalysts, solar cells, and gas sensors. In this study, we investigated the effects of intratracheal instillation of cerium oxide nanoparticles on the inflammatory responses in mice. The number of neutrophils in bronchoaveolar lavage (BAL) fluids was significantly elevated on day 1 after instillation. Inflammatory cytokines, such as interleukin (IL)-1, tumor necrosis factor (TNF)-α, and IL-6, were also increased in BAL fluid and the cytokine increase initiated the differentiation of naive T cells, followed by the induction of Th1-type cy-tokines [IL-12 and interferon (IFN)-γ] and Th2-type cytokines (IL-4, IL-5, and IL-10). The secretion of Th1-type cytokines was more dominant than that of Th2-type cytokines. The inflammatory responses were maintained for 28 days by a positive feedback stimulation of IFN-y and IL-10. In the lung, the expression of inflammatory genes was increased in a time-dependent manner, and granuloma formation appeared on day 14 after instillation. This suggests that intratracheal instillation of cerium oxide nanoparticles causes a delayed-type hypersensitivity reaction and lung fibrosis in mice. © 2010 The Pharmaceutical Society of Japan.

Cuong T.D.,Catholic University of Daegu | Hung T.M.,Catholic University of Daegu | Kim J.-C.,Korea Research Institute of Chemical Technology | Huh J.-I.,Korea Research Institute of Chemical Technology | And 8 more authors.
Planta Medica | Year: 2011

Two new lignans, (2R,3R)-2β-(4-hydroxy-3α-methoxybenzyl)-3-(4- hydroxy-3'-methoxybenzyl) -γ- butyrolactone 2-O-(β-D-glucopyranoside) (1) and (1S,2R,3S)-dimethyl-1,2,3,4-tetrahydro-3,6,7-trihydroxy-1-(3,4- dihydroxyphenyl)naphthalene-2,3-dicarboxylate (2) together with nine known compounds (3-11) were isolated from the ethyl acetate fraction of the roots of Pulsatilla koreana. Their chemical structures were established based on physicochemical and spectroscopic data analyses. All isolates were investigated for their inhibition effects against the classical pathway of the complement system. Among them, compound 6 showed significant inhibitory activity with an IC 50 value of 75.9 μM, compounds 8 and 9 had moderate effects with IC 50 values of 182.2 and 166.5 μM, respectively. © Georg Thieme Verlag KG Stuttgart - New York.

PubMed | National Institute of Toxicological Research
Type: Comparative Study | Journal: Allergology international : official journal of the Japanese Society of Allergology | Year: 2010

In previous studies, several strains of mice were used as chemical-induced skin irritation models to identify immunological hazards and elucidate the molecular and cellular mechanisms by which irritant dermatitis disease occur. BALB/c and C57BL/6 mice have been used for most of these experiments. Although there are some differences in the immune response to chemical allergens between these strains, few studies have been conducted to determine what regulatory factors contribute to these variations.To investigate the cause of high responses to skin irritation in C57BL/6 mice that are widely used to study atopic dermatitis, changes in various immune-related factors such as ear thickness, myeloperoxidase activity, lymph node weight, IgE concentration and cytokine concentration were measured in C57BL/6 and BALB/c mice following phthalic anhydride (PA) treatment.Based on analysis of the skin irritation, C57BL/6 mice showed a greater skin irritation to PA than BALB/c mice, although the IgE concentration and auricular lymph node weight did not contribute to this difference in the response. However, the concentration of several cytokines and chemokines (interleukin [IL]-6 and vascular endothelial growth factor [VEGF], keratinocyte-derived chemokine [KC] and regulated on activation normal T cell expressed and secreted [RANTES]) were significantly higher in C57BL/6 mice than BALB/c mice following treatment with PA.Our results suggest that several of the cytokines and chemokines secreted from irritant site could contribute to the regulation mechanism responsible for the difference in the skin irritation among various strains of mice following exposure to PA.

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