• Title/Summary/Keyword: human toxicity

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Toxic Effects of Alumina Nanoparticles in Rat Cerebrums and Kidneys (산화알루미늄 나노물질이 랫드의 대뇌와 신장에 미치는 영향)

  • Jo, Eunhye;Seo, Gyun-Baek;Kim, Hyunmi;Choi, Kyunghee;Kwon, Jung-Taek;Kim, Philje;Eom, Igchun
    • Journal of Environmental Health Sciences
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    • v.42 no.1
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    • pp.27-33
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    • 2016
  • Objectives: Alumina nanoparticles ($Al_2O_3$, Al-NPs) are used for various purposes, including as coating agents and paint additives. Their potential toxicity has raised concern for human health. This study focuses on exploring the toxic effects on the brain and kidneys caused by Al-NPs exposure in rats. Methods: The animals were orally administered Al-NPs at 10, 50 and 100 mg/kg body weight for 28 days following OECD TG 407. To determine the targeted toxicity of Al-NPs, histopathological examination and gene expression analysis were conducted on the rats. Results: The Al-NPs treatment induced kidney tubular dilatation. In the rat cerebrums, the expression levels of 126 genes experienced two-fold or greater increases in response to Al-NPs, including other genes encoding proteins involved in cell differentiation, transcription and signal transduction. In the rat kidneys, the expression levels of 152 genes also showed two-fold or greater increases in response to Al-NPs, including other genes encoding proteins involved in apoptosis, transcription and signal transduction. Conclusion: These results suggest that exposure to Al-NPs influences cellular signal pathways of kidney and cerebrum, and it can be a toxic indicators of nanometrials.

Magnesium Sulfate Induced Toxicity in Vitro in AGS Gastric Adenocarcinoma Cells and in Vivo in Mouse Gastric Mucosa

  • Zhang, Xulong;Bo, Agula;Chi, Baofeng;Xia, Yuan;Su, Xiong;Sun, Juan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.1
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    • pp.71-76
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    • 2015
  • Magnesium sulfate is widely used as a food additive and as an orally administered medication. The aim of this study was to evaluate the possible cytotoxicity of magnesium sulfate on AGS human gastric adenocarcinoma cells and gastric mucosa in mice. A trypan blue exclusion assay was used to determine the reduction in viability of AGS cells exposed to magnesium sulfate, and then effects on cell proliferation were quantified. The role of magnesium sulfate-mediated pro-inflammatory cytokine production in AGS cells was also investigated. mRNA expression for IL-$1{\beta}$, IL-6, IL-8, and TNF-${\alpha}$ was determined by RT-PCR, and secretion of these cytokines was measured by ELISA. Immunohistochemical evaluation of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ expression was conducted in mouse gastric mucosa. Addition of 3 to 50 mM magnesium sulfate to AGS cells inhibited both cell proliferation and cell viability in a dose-dependent manner. Magnesium sulfate had little effect on production of IL-$1{\beta}$ or IL-6 but significantly inhibited production of IL-8. The animal model demonstrated that magnesium sulfate induced production of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$. These preliminary data suggest that magnesium sulfate had a direct effect on the stomach and initiates cytotoxicity in moderate concentrations and time periods by inhibiting viability a nd proliferation of AGS cells and by regulating expression and/or release of pro-inflammatory cytokines.

Bacteriological Characteristics of Unidentified Vibrio sp., Hemolysin Producer Isolates front Brackish Water -1. Bacteriological Characteristics of Vibrio sp., D9 (V. kumkang) Similar to V. mimicus (기수에서 분리된 용혈독소를 생산하는 미분류 Vibrio sp.의 세균학적 특징 -1. V. mimicus와 유사한 Vibrio sp. D9의 세균학적 특성)

  • KIM Young-Man;OH Hee-Kyung
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.33 no.6
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    • pp.585-590
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    • 2000
  • A hemolysin producing strain was isolated from Kum rivet estuary located in west part of Korea. In the process of identification the isolated strain was similar to V. mimicus but did not show characteristics of known Vibrio species; therefore, the strain was designated as Vibrio sp. D9 ( V. kumkang) tentatively and further identification study was carried out by comparing its bacteriological characteristics, Morphologically Vibrio sp. D9 was a typical straight roe with a polar flagellium. Among known Vibrio species no identical strains were found when using automatic bacteria identification system ($MicioLog^(TM)$system, release 4.0, Biolog Inc., USA) which evaluated the ability of metabolizing 95 kinds of carbon and nitrogen sources. Vibrio sp. D9 showed 18 and 13 different responses as compared to V. mimicus and V. cholerae, respectively. Clear hemolysis zones were observed with the strain against human and sheep blood agar plate, Hemolytic toxicity was confirmed by strong vascular permeability and fatal toxicity against mouse was also observed. Thus the strain was a pathogenic vibrio. Growth conditions for Vibrio sp. D9 were salinity of $0{\~}5.0{\%}$, pH of $6.4{\~}9.8$, temperature of $15{\~}41^{\circ}C$, respectively.

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Enhancement of a Liver Form of Cytosolic Phospholipase $A_2$ Activity by Methylmercury

  • Huh, Don-Haeng;Kang, Mi-Sun;Sohn, Dong-Hun;Na, Doe-Sun;Kim, Dae-Kyong
    • BMB Reports
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    • v.31 no.2
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    • pp.189-195
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    • 1998
  • Methylmercury (MeHg), which is widely distributed in the environment, is well known for both its acute and chronic poisoning effects on the human health; however, the precise biochemical mechanisms by which this compound elicits its toxicity in a cellular level are still poorly understood. To examine whether MeHg-induced liver injury involves activation of Phospholipase $A_2$ ($PLA_2$), the $PLA_2$ activity of control and MeHg-administrated livers was measured. MeHg stably enhanced a liver form of cytosolic $PLA_2$ activity, which exhibited several biochemical properties similar to those of the 100 kDa $cPLA_2$, except in its elution profile of a DEAE-5PW HPLC, and it migrated as a molecular weight of 80 kDa in Western blot analysis. This blotting analysis also indicated that the MeHg-induced enhancement of the activity could be due to the increase in the amount of the enzyme protein rather than a stable modification of the enzyme such as phosphorylation. Our data also showed the higher myeloperoxidase activity in MeHg-administrated liver than in the control, suggesting that this increase in the amounts of the 80 kDa $PLA_2$ and its activity may be resulted from infiltration of neutrophils into the liver during a hepatic injury process such as MeHg-induced inflammation. Taken together, these data suggest that MeHg-induced liver injury may be mediated by activation of the 80 kDa form of liver cytosolic $PLA_2$.

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The effects of estradiol and its metabolites on the regulation of CYP1A1 expression.

  • Euno, Joung-Ki;Yhong, Sheen-Yhun
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2002.10a
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    • pp.170-170
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    • 2002
  • College of Pharmacy, Ewha womans University, Seoul, 120-750, Korea 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, and reproductive and developmental toxicity. Dramatic differences in dioxin toxicity have been observed between the sexes of some animal species, suggesting hormonal modulation of dioxin action. Many studies have been reported and propose several mechanisms of anti-estrogenic effects of TCDD. In contrast, the effect of estrogen on the regulation of CYP1A1 are not clear at present. There are several reports showing conflicting results. It seems that induction/inhibition of CYP1A1 may be dependent on cell-type and concentration. The purpose of this study was to investigate the regulation of TCDD-induced CYP1A1 gene expression by estradiol and its metabolites. We examined whether estradiol and its metabolites altered TCDD-mediated induction of CYP1A1 enzyme activity. 17 ${\beta}$ estradiol and 16 ${\alpha}$ estriol at non cytotoxic concentrations caused a significant concentration dependent decline of TCDD-induced EROD activity To determine whether reduced EROD activity reflected altered CYP1A1 mRNA expression, we measured CYP1A1 mRNA level by RT-PCR. And to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level, we also peformed transient transfection with an AhR responsive reporter plasmid containing the 5' flanking region of the human CYP1A1 gene to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level.

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Anti-angiogenic, Anti-cell Adhesion Switch from Halophilic Enterobacteria

  • Lim, Jong Kwon;Seo, Hyo Jin;Kim, Eun Ok;Meydani, Mohsen;Kim, Jong Deog
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.3
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    • pp.156-162
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    • 2006
  • The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/mL$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited non-activated U937 monocytic cell adhesion to HUVECs activated with IL-$1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with IL-$1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to IL-$1{\beta}$ stimulated HUVECs was completely suppressed by 121% at a concentration of 18.5 ug/mL. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin and VE-cadherin to NF-kB based on western bolt analysis. And also inhibited IL-1-stimulated HUVEC expression of the adhesion molecules, ICAM-1 by 40%, VCAM-1 by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities and non-toxicity may be expected from these results.

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Identification of Anti-Angiogenic and Anti-Cell Adhesion Materials from Halophilic Enterobacteria of the Trachurus japonicus

  • Lim, Jong-Kwon;Seo, Hyo-Jin;Kim, Eun-Ok;Meydani, Mohsen;Kim, Jong-Deog
    • Journal of Microbiology and Biotechnology
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    • v.16 no.10
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    • pp.1544-1553
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    • 2006
  • The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/ml$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited cell adhesion that non-activated U937 monocytic cell adhesion to HUVECs activated with $IL-1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with $IL-1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to $IL-1{\beta}$-stimulated HUVECs was completely suppressed by 121% at a concentration of $18.5{\mu}g/ml$. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin, and VE-cadherin to NF-kB, based on western bolt analysis. It also inhibited IL-l-stimulated HUVEC expression of the adhesion molecules, ICAM-l by 40%, VCAM-l by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities, and non-toxicity may be expected from these results.

Clostridium difficile Toxin A Inhibits the Kinase Activity of Extracellular Signal-Related Kinases 1 and 2 Through Direct Binding

  • Seok, Heon;Nam, Hyo-Jung;Nam, Seung-Taek;Kang, Jin-Ku;Kim, Sung-Kuk;Chang, Jong-Soo;Ha, Eun-Mi;Park, Young-Joo;Kim, Ho
    • Journal of Microbiology and Biotechnology
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    • v.22 no.2
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    • pp.170-175
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    • 2012
  • Clostridium difficile toxin A glucosylates Rho family proteins, resulting in actin filament disaggregation and cell rounding in cultured colonocytes. Given that the cellular toxicity of toxin A is dependent on its receptor binding and subsequent entry into the cell, we herein sought to identify additional colonocyte proteins that might bind to toxin A following its internalization. Our results revealed that toxin A interacted with ERK1 and ERK2 in two human colonocyte cell lines (NCM460 and HT29). A GST-pulldown assay also showed that toxin A can directly bind to ERK1 and ERK2. In NCM460 cells exposed to PMA (an ERK1/2 activator), the phosphorylation of ERK1/2 did not affect the interaction between toxin A and ERK1/2. However, an in vitro kinase assay showed that the direct binding of toxin A to ERK1 or ERK2 inhibited their kinase activities. These results suggest a new molecular mechanism for the cellular toxicity seen in cells exposed to toxin A.

Comparison of Distribution and Inflammatory Response by Diameter and Shape of Silver Nanoparticles (은나노 입자의 입경 크기 및 형태에 따른 체내 동태 및 염증 반응)

  • Kim, Soo-Nam;Roh, Jin-Kyu;Kang, Min-Sung;Han, Young-Ah;Lee, Byoung-Seok;Kim, Young-Hun;Park, Kwang-Sik;Choi, Kyung-Hee;Park, Eun-Jung
    • Environmental Analysis Health and Toxicology
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    • v.25 no.3
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    • pp.215-222
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    • 2010
  • The market size of engineered nanoparticles is rapidly increasing due to the fast application of nanotechnologies into different industries and consumer products. The development of new technology and materials has improved human's quality of life, but it also entails the possibility of exposure to new materials. In this study, we compared the distribution in the body by the inflow of silver nanoparticles having another diameter and shape at 1 h or 24 h after injection via the tail vein. And, we compared the cell composition and cytokine concentration in BAL fluid, and histopathological changes. As results, discharge of silver nanoparticles having small diameter and sphere shape was more rapid than that of big diameter or plate shape. It is estimated that the toxicity in liver and lung was proportional to accumulation level. The persistence of inflammation was also longer in mice treated with plate shape. Consequently, we suggest that the first choice of silver nanoparticles having small diameter and sphere shape in applying is desirable.

The Current Status of Strong Acids Production, Consumption, and Spill Cases in Korea (사고 누출 화학물질 중 강산의 생산, 사용 현황 및 사고 사례 분석)

  • Shin, Doyun;Moon, Hee Sun;Yoon, Yoon Yeol;Yun, Uk;Lee, Yunho;Ha, Kyoochul;Hyun, Sung Pil
    • Journal of Soil and Groundwater Environment
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    • v.19 no.6
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    • pp.6-12
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    • 2014
  • We reviewed literature focusing on the amounts of domestic production, distribution, and consumption of strong acids and their spill cases. In particular, we investigated the chemistry and toxicity of four strong acids classified as "accident preparedness substances," including hydrochloric, nitric, sulfuric, and hydrofluoric acid. We recommend sulfuric and hydrofluoric acid as the chemicals of priority control based on the amounts used and toxicity. An advanced prevention/response system needs to be established along with an improved human and social infrastructure to prevent and efficiently respond to chemical accidents. Understanding the behavior and transport of spilled strong acids in the soil and groundwater environments requires a multi-disciplinary approach since they go through a variety of chemical and biogeochemical reactions with complex geomedia. However, no such research has been done in this area in Korea to the best of our knowledge. We expect the results of this study to contribute as basic data to future research.