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Toxicological Investigation of Radioactive Uranium in Seawater.

Toxicological Research.2012;28(1):67-71.

Trace uranium detection measurement was performed using DNA immobilized on a graphite pencil electrode (DGE). The developed probe was connected to the portable handheld voltammetric systems used for seawater analysis. The sensitive voltammogram was obtained within only 30 s accumulation time, and the anodic stripping working range was attained at 100~800 microg/l U and 10~50 microg/l. The statistic relative standard deviation of 30.0 mg/l with the 15th stripping was 0.2115. Here, toxicological and analytical application was performed in the seawater survey in a contaminated power plant controlling water. The results were found to be applicable for real-time toxicological assay for trace control.
DNA ; Electrodes ; Graphite ; Power Plants ; Seawater ; Uranium ; Seawater

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The Toxicity and Anti-cancer Activity of the Hexane Layer of Melia azedarach L. var. japonica Makino's Bark Extract.

Hyun Woo KIM ; Se Chan KANG

Toxicological Research.2012;28(1):57-65.

In this study, the 4-week oral toxicity and anti-cancer activity of the hexane layer of Melia azedarach L. var. japonica Makino's bark extract were investigated. We carried out a hollow fiber (HF) assay and 28-day repeated toxicity study to confirm the anti-cancer effect and safety of the hexane layer. The HF assay was carried out using an A549 human adenocarcinoma cell via intraperitoneal (IP) site with or without cisplatin. In the result, the 200 mg/kg b.w of hexane layer with 4 mg/kg b.w of cisplatin treated group, showed the highest cytotoxicity aginst A549 carcinoma cells. For the 28-day repeated toxicity study, 6 groups of 10 male and female mice were given by gavage 200, 100, or 50 mg/kg b.w hexane layer with or without 4 mg/kg b.w of cisplatin against body weight, and were then sacrificed for blood and tissue sampling. The subacute oral toxicity study in mice with doses of 200, 100, and 50 mg/kg b.w hexane layer showed no significant changes in body weight gain and general behavior. The cisplatin-treated group significantly decreased in body weight compared to the control group but regained weight with 100 and 200 mg/kg b.w of hexane layer. The biochemical analysis showed significant increase in several parameters (ALT, total billirubin, AST, creatinine, and BUN) in cisplatin-treated groups. However, in the group given a co-treatment of hexane layer (200 mg/kg b.w), levels of these parameters decreased. In hematological analysis, cisplatin induced the reduction of WBCs and neutrophils but co-treatment with hexane layer (100 and 200 mg/kg b.w) improved these toxicities caused by cisplatin. The histological profile of the livers showed eosinophilic cell foci in central vein and portal triad in cisplatin treated mice. These results show that hexane layer might have an anti-cancer activity and could improve the toxicity of cisplatin.
Adenocarcinoma ; Animals ; Body Weight ; Cisplatin ; Creatinine ; Eosinophils ; Female ; Humans ; Liver ; Male ; Melia ; Melia azedarach ; Mice ; Neutrophils ; Veins

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The Safety Evaluation of a Potent Angiogenic Activator, Synthetic Peptide (SFKLRY-NH2) for the Skin Application.

Dong Ha KIM ; Yun Young LIM ; Hyeong Mi KIM ; So Young KIM ; Beom Joon KIM ; Sung Gil PARK ; Taehoon LEE ; Soo Muk CHO

Toxicological Research.2012;28(1):51-56.

A novel synthetic hexapeptide (SFKLRY-NH2) that displays angiogenic activity has been identified by positional scanning of a synthetic peptide combinatorial library (PS-SPCL). This study was carried out to investigate the irritation of the SFKLRY-NH2 on the skin. The tests were performed on the basis of Korea Food and Drug Administration (KFDA) guidelines. In results, cell toxicity is not appeared for SFKLRY-NH2 in HaCaT cells and B16F10 cells. SFKLRY-NH2 induced no skin irritation at low concentration (10 microM), mild irritation at high concentration (10mM). We consider that this result is helpful for saying about the safety of SFKLRY-NH2 in clinical use.
Korea ; Oligopeptides ; Peptide Library ; Skin ; United States Food and Drug Administration

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Suppressive Effect of Zinc on the Formation of Colonic Preneoplastic Lesions in the Mouse Fed High Levels of Dietary Iron.

Hyunji PARK ; Bong Su KANG ; Dang Young KIM ; Ja Seon YOON ; Jae Hwang JEONG ; Sang Yoon NAM ; Young Won YUN ; Jong Soo KIM ; Beom Jun LEE

Toxicological Research.2012;28(1):39-49.

We investigated the effect of zinc on the formation of colonic aberrant crypt foci induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in mice with high iron diet (HFe; 450 ppm iron). Six-week old ICR mice were fed on high iron diets with combination of three different levels of zinc in diets, low-zinc (LZn; 0.01 ppm), medium-zinc (MZn; 0.1 ppm), and high-zinc (HZn; 1 ppm) for 12 weeks. Animals were received weekly intraperitoneal injections of AOM (10 mg/kg B.W. in saline) for 3 weeks followed by 2% DSS (molecular weight 36,000~50,000) in the drinking water for a week. To confirm the iron storage in the body, the hepatic iron concentration has been determine chemically and compared with histological assessment visualized by Prussian blue reaction. Aberrant crypt (AC) and aberrant crypt foci (ACF) were analyzed in the colonic mucosa of mouse fed high dietary iron. Superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) level were also investigated. Apoptosis in the preneoplastic lesion was determined by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL). In addition, immunohistochemistry of beta-catenin was also performed on the mucous membrane of colon. The number of large ACF (> or = 4 AC/ACF), which possess greater tumorigenic potential, was significantly lower in MZn and HZn groups compared with LZn group. Cytosolic SOD activity in the liver was significantly higher in HZn group compared with LZn group. Hepatic MDA level was decreased significantly in HZn group compared with MZn and LZn groups. Apoptotic index was significantly higher in HZn group. Taken together, these findings indicate that dietary zinc might exert a protective effect against colonic preneoplastic lesion induced by AOM/DSS in ICR mice with high iron status, and suggest that dietary supplement of zinc might play a role in suppressing colon carcinogenesis in mice.
Aberrant Crypt Foci ; Animals ; Apoptosis ; Azoxymethane ; beta Catenin ; Colon ; Cytosol ; Dextrans ; Diet ; Dietary Supplements ; Drinking Water ; Ferrocyanides ; Immunohistochemistry ; Injections, Intraperitoneal ; Iron ; Iron Overload ; Iron, Dietary ; Liver ; Mice ; Mice, Inbred ICR ; Mucous Membrane ; Prussian Blue Reaction ; Sodium ; Sulfates ; Superoxide Dismutase ; Zinc

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Methanolic Extract Isolated from Root of Lycoris aurea Inhibits Cancer Cell Growth and Endothelial Cell Tube Formation In Vitro.

Moo Rim KANG ; Chang Woo LEE ; Jieun YUN ; Soo Jin OH ; Song Kyu PARK ; Kiho LEE ; Hwan Mook KIM ; Sang Bae HAN ; Hyoung Chin KIM ; Jong Soon KANG

Toxicological Research.2012;28(1):33-38.

In this study, we investigated the effect of methanolic extract isolated from the root of Lycoris aurea (LA) on the growth of cancer cells and the tube formation activity of endothelial cells. Various cancer cells were treated with LA at doses of 0.3, 1, 3, 10 or 30 microg/ml and LA significantly suppressed the growth of several cancer cell lines, including ACHN, HCT-15, K-562, MCF-7, PC-3 and SK-OV-3, in a dose-dependent manner. We also found that LA induced cell cycle arrest at G2/M phase in ACHN renal cell adenocarcinoma cells. Further study demonstrated that LA concentration-dependently inhibited the tube formation, which is a widely used in vitro model of reorganization stage of angiogenesis, in human umbilical vein endothelial cells. Collectively, these results show that LA inhibits the growth of cancer cells and tube formation of endothelial cells and the growth-inhibitory effect of LA might be mediated, at least in part, by blocking cell cycle progression.
Carcinoma, Renal Cell ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; Endothelial Cells ; Human Umbilical Vein Endothelial Cells ; Lycoris ; Methanol

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Acute Pulmonary Toxicity and Body Distribution of Inhaled Metallic Silver Nanoparticles.

Jung Taek KWON ; Arash MINAI-TEHRANI ; Soon Kyung HWANG ; Ji Eun KIM ; Ji Young SHIN ; Kyeong Nam YU ; Seung Hee CHANG ; Dae Seong KIM ; Yong Taek KWON ; In Ja CHOI ; Yun Hee CHEONG ; Jun Sung KIM ; Myung Haing CHO

Toxicological Research.2012;28(1):25-31.

The purpose of this study was to determine the acute pulmonary toxicity of metallic silver nanoparticles (MSNPs, 20.30 nm in diameter). Acute pulmonary toxicity and body distribution of inhaled MSNPs in mice were evaluated using a nose-only exposure chamber (NOEC) system. Bronchoalveolar lavage (BAL) fluid analysis, Western blotting, histopathological changes, and silver burdens in various organs were determined in mice. Mice were exposed to MSNPs for 6 hrs. The mean concentration, total surface area, volume and mass concentrations in the NOEC were maintained at 1.93 x 10(7) particles/cm3, 1.09 x 10(10) nm2/cm3, 2.72 x 10(11) nm3/cm3, and 2854.62 microg/m3, respectively. Inhalation of MSPNs caused mild pulmonary toxicity with distribution of silver in various organs but the silver burdens decreased rapidly at 24-hrs post-exposure in the lung. Furthermore, inhaled MSNPs induced activation of mitogen-activated protein kinase (MAPK) signaling in the lung. In summary, single inhaled MSNPs caused mild pulmonary toxicity, which was associated with activated MAPK signaling. Taken together, our results suggest that the inhalation toxicity of MSNPs should be carefully considered at the molecular level.
Animals ; Blotting, Western ; Bronchoalveolar Lavage ; Inhalation ; Lung ; Mice ; Nanoparticles ; Protein Kinases ; Silver

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Involvement of Caenohabditis elegans MAPK Signaling Pathways in Oxidative Stress Response Induced by Silver Nanoparticles Exposure.

Ji Yeon ROH ; Hyun Jeong EOM ; Jinhee CHOI

Toxicological Research.2012;28(1):19-24.

In the present study, toxicity of silver nanoparticles (AgNPs) was investigated in the nematode, Caenohabditis elegans focusing on the upstream signaling pathway responsible for regulating oxidative stress, such as mitogen-activated protein kinase (MAPK) cascades. Formation of reactive oxygen species (ROS) was observed in AgNPs exposed C. elegans, suggesting oxidative stress as an important mechanism in the toxicity of AgNPs towards C. elegans. Expression of genes in MAPK signaling pathways increased by AgNPs exposure in less than 2-fold compared to the control in wildtype C. elegans, however, those were increased dramatically in sod-3 (gk235) mutant after 48 h exposure of AgNPs (i.e. 4-fold for jnk-1 and mpk-2; 6-fold for nsy-1, sek-1, and pmk-1, and 10-fold for jkk-1). These results on the expression of oxidative stress response genes suggest that sod-3 gene expression appears to be dependent on p38 MAPK activation. The high expressions of the pmk-1 gene 48 h exposure to AgNPs in the sod-3 (gk235) mutant can also be interpreted as compensatory mechanisms in the absence of important stress response genes. Overall results suggest that MAPK-based integrated stress signaling network seems to be involved in defense to AgNPs exposure in C.elegans.
Caenorhabditis elegans ; Gene Expression ; Nanoparticles ; Oxidative Stress ; p38 Mitogen-Activated Protein Kinases ; Protein Kinases ; Reactive Oxygen Species ; Silver

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Mouse Single Oral Dose Toxicity Test of Bupleuri Radix Aqueous Extracts.

Kyung Hu KIM ; Cheol Ou GAM ; Seong Hun CHOI ; Sae Kwang KU

Toxicological Research.2012;28(1):11-18.

The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, LD50 (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.
Animals ; Body Weight ; Feces ; Female ; Humans ; Korea ; Lethal Dose 50 ; Male ; Mice ; Mice, Inbred ICR ; Organ Size ; Toxicity Tests ; United States Food and Drug Administration

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Synthetic Prion Peptide 106-126 Resulted in an Increase Matrix Metalloproteinases and Inflammatory Cytokines from Rat Astrocytes and Microglial Cells.

Kibbeum SONG ; Ji Young NA ; Myung Hoon OH ; Sokho KIM ; Young Ha KIM ; Byung Yong PARK ; Gi Wook SHIN ; Bumseok KIM ; Myungjo YOU ; Jungkee KWON

Toxicological Research.2012;28(1):5-9.

It has been shown that the accumulation of prion in the cytoplasm can result in neurodegenerative disorders. Synthetic prion peptide 106-126 (PrP) is a glycoprotein that is expressed predominantly by neurons and other cells, including glial cells. Prion-induced chronic neurodegeneration has a substantial inflammatory component, and an increase in the levels of matrix metalloproteinases (MMPs) may play an important role in neurodegenerative development and progression. However, the expression of MMPs in PrP induced rat astrocytes and microglia has not yet been compared. Thus, in this study, we examined the fluorescence intensity of CD11b positive microglia and Glial Fibrillary Acidic Protein (GFAP) positive astrocytes and found that the fluorescent intensity was increased following incubation with PrP at 24 hours in a dose-dependent manner. We also observed an increase in interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) protein expression, which are initial inflammatory cytokines, in both PrP induced astrocytes and microglia. Furthermore, an increase MMP-1, 3 and 11 expressions in PrP induced astrocytes and microglia was observed by real time PCR. Our results demonstrated PrP induced activation of astrocytes and microglia respectively, which resulted in an increase in inflammatory cytokines and MMPs expression. These results provide the insight into the different sensitivities of glial cells to PrP.
Animals ; Astrocytes ; Cytokines ; Cytoplasm ; Fluorescence ; Glial Fibrillary Acidic Protein ; Glycoproteins ; Interleukin-1beta ; Matrix Metalloproteinases ; Microglia ; Neurodegenerative Diseases ; Neuroglia ; Neurons ; Rats ; Real-Time Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha

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Skin Sensitization Study of Bee Venom (Apis mellifera L.) in Guinea Pigs.

Sang Mi HAN ; Gwang Gill LEE ; Kyun Kyu PARK

Toxicological Research.2012;28(1):1-4.

Bee venom (Apis mellifera L., BV) has been used as a cosmetic ingredient for antiaging, anti-inflammatory and antibacterial functions. The aim of this study was to access the skin sensitization of BV, a Buehler test was conducted fifty healthy male Hartley guinea pigs with three groups; Group G1 (BV-sensitization group, 20 animals), group G2 (the positive control-sensitization group, 20 animals), and group G3 (the ethyl alcohol-sensitization group, 10 animals). The exposure on the left flank for induction was repeated three times at intervals of one week. Two weeks after the last induction, the challenge was performed on the right flank. No treatment-related clinical signs or body weight changes were observed during the study period. The average skin reaction evaluated by erythema and edema on the challenge sites and sensitization rate in the BV-sensitization group at 30 hours were 0.0 and 0%, respectively, which are substantially low compared with in positive control group (average skin reaction: 0.55, sensitization rate: 40%) and identical with in vehicle control group, representing a weak sensitizing potential. The average skin reaction and sensitization rate observed at 54 hours were 0.0 and 0% in the BV-sensitization group, respectively, and 0.25 and 20% in the positive control group, respectively. It was concluded that BV classified to Grade I, induced no sensitization when tested in guinea pigs and may provide a developmental basis for a cosmetic ingredient or external application for topical uses.
Animals ; Bee Venoms ; Bees ; Body Weight Changes ; Cosmetics ; Edema ; Erythema ; Guinea ; Guinea Pigs ; Humans ; Male ; Skin

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