• Title/Summary/Keyword: toxic mechanism

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Reduction effects of N-acetyl-L-cysteine, L-glutathione, and indole-3-acetic acid on phytotoxicity generated by methyl bromide fumigation- in a model plant Arabidopsis thaliana (모델식물 애기장대에 대한 훈증제 메틸브로마이드의 약해발생 및 N-acetyl-L-cysteine, L-glutathione, indole-3-acetic acid의 약해억제 효과)

  • Kim, Kyeongnam;Kim, Chaeeun;Park, Jungeun;Yoo, Jinsung;Kim, Woosung;Jeon, Hwang-Ju;Kim, Jun-Ran;Lee, Sung-Eun
    • Korean Journal of Environmental Biology
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    • v.39 no.3
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    • pp.354-361
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    • 2021
  • Understanding the phytotoxic mechanism of methyl bromide (MB), an essential fumigant during the quarantine and pre-shipment process, is urgently needed to ensure its proper use and reduce international economic losses. In a previous study, two main MB-induced toxic mechanisms such as reactive oxygen species (ROS) and auxin distribution were selected by analyzing transcriptomic analysis. In the study, a 3-week-old A. thaliana was supplied with 1 mM ROS scavengers [N-acetyl-L-cysteine (NAC) or L-glutathione (GSH)] and 1µM indole-3-acetic acid(IAA) three times every 12 h, and visual and gene expression assessments were performed to evaluate the reduction in phytotoxicity by supplements. Phytotoxic effects on the MB-4h exposed group were decreased with GSH application compared to the other single supplements and a combination of supplements at 7 days post fumigation. Among these supplements, GSH at a concentration of 1, 2, and 5mM was suppled to A. thaliana with MB-fumigation. During a long-term observation of 2 weeks after the fumigation, 5 mM GSH application was the most effective in minimizing MB-induced phytotoxic effects with up-regulation of HSP70 expression and increase in main stem length. These results indicated that ROS was a main key factor of MB-induced phytotoxicity and that GSH can be used as a supplement to reduce the phytotoxicity of MB.

Neutrophil Chemotactic Activity in Bronchoalveolar Lavage Fluid of the Rats Exposed to Hyperoxia (고농도의 산소에 노출시킨 쥐의 기관지폐포세척액내 호중구 화학주성활성화도)

  • Song, Jeong Sup;Lee, Sook Young;Moon, Wha Sik;Park, Sung Hak
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.4
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    • pp.547-557
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    • 1996
  • Background : An excessive accumulation of neutrophils in lung tissue has been known to play an important role in mediating the tissue injury among the adult respiratory distress syndrome, idiopathic pulmonary fibrosis and cystic fibrosis by releasing toxic oxygen radicals and proteolytic enzymes. Therefore, it is important to understand a possible mechanism of neutrophil accumulation in lung tissue. In many species, exposure to hyperoxic stimuli can cause changes of lung tissues very similar to human adult respiratory distress syndrome and neutrophils are also functioning as the main effector cells in hyperoxic lung injury. The purpose of the present study was to examine whether neutrophils function as a key effector cell and to study the nature of possible neutrophil chemotactic factors found in bronchoalveolar lavage fluid from the hyperoxia exposed rats. Methods : We exposed the rats to the more than 95% oxygen for 24, 48, 60 arid 72 hours and bronchoalveolar lavage(BAL) was performed. Neutrophil chemotactic activity was measured from the BAT- fluid of each experimental groups. We also evaluated the molecular weight of neutrophil chemotactic tractors using fast performance liquid chromatography and characterized the substances by dialyzer membrane and heat treatment. Results : 1) The neutrophil proportions in bronchoalveolar lavage fluid began to rise from 48 hours after oxygen exposure, and continued to be significantly increased with exposure times. 2) chemotactic index for neutrophils in lung lavages from rats exposed to hyperoxia was significantly higher in 48 hours group than in control group, and was significantly increased with exposure time. 3) No deaths occured until after 48 hours of exposure. However, mortality rates were increased to 33.3 % in 60 hours group and 81.3 % in 72 fours group. 4) Gel filtration using fast performance liquid chromatography disclosed two peaks of neutrophil chemotactic activity in molecular weight of 104,000 and 12,000 daltons. 5) Chemotactic indices of bronchoalveolar lavage fluid were significantly deceased when bronchoalveolar lavage fluid was treated with heat ($56^{\circ}C$ for 30 min or $100^{\circ}C$ for 10 min) or dialyzed (dialyzer membrane molecular weight cut off : 12,000 daltons). Conclusion : These results suggested that the generation of neutrophil chemotactic factor and subsequent neutrophil influx into the lungs are playing an important roles in hyperoxia-induced acute lung injury. Neutrophil chemotactic factor in the lung lavage fluids consisted of several distinct components having different molecular weight and different physical characteristics.

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Cumulative Risk Assessment of Organophosphorus Pesticides in the Diet (식품을 통한 유기인계농약류의 동시노출위해성평가)

  • 이효민;한지연;윤은경;김효미;황인균;최동미;이강봉;원경풍;송인상
    • Journal of Food Hygiene and Safety
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    • v.16 no.1
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    • pp.21-26
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    • 2001
  • Risk assessment traditionally are conducted on individual chemicals; however, humans are exposed to multiple chemicals in daily life. The organophosphorus (OP) pesticides are considered in a single risk assessment because they act by a common mechanism of toxicity, and there is likely to be expose to multiple OP pesticides simultaneously or sequentially. The OP pesticides act by inhibiting the enzyme acetylcholinesterasc (AChE) and have available extensive database. AChE is widely distributed throughout the body, most importantly in the nervous system. Inhibition of AChE results in accumulation of acetylcholine in the nervous system that results in clinical signs of cholinergic toxicity, including increased salivation and lacrimation, nausea and vomiting, muscle fasciculation, lethargy and fatigue, among others. To conduct an exposure assessment for pesticides in the diet, we need to know the food consumption patterns of the populations, and the pesticide residue levels in the foods that are consumed. This study was conducted to identify cumulative dietary risk due to multiple OP pesticides that can be exposed through various foods. Total 22 food samples including cereals, vegetables and fruits were collected randomly two times from food markets in several sites (4 cities). The subjected foods were selected by regarding of highly consumed foods to general Korean people. The 12 OP pesticides including Acephate, Azinphos-methyl, Chlorpyrifos, and Diazinon were monitored. For the exposure assessment, general adult group of 60 kg body weight was regarded as target population and food consumption data suggested by Lee et al. (2000) were used as consumed value of individual food. Analyses of samples for OP pesticides have been carried out according to the multiclass multiresidue analysis method and acephate and methamidophos analysis method of Korea Food Code. In general the levels of OP pesticides found in the food samples were very low or not detected.

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Innovative Technology of Landfill Stabilization Combining Leachate Recirculation with Shortcut Biological Nitrogen Removal Technology (침출수 재순환과 생물학적 단축질소제거공정을 병합한 매립지 조기안정화 기술 연구)

  • Shin, Eon-Bin;Chung, Jin-Wook;Bae, Woo-Keun;Kim, Seung-Jin;Baek, Seung-Cheon
    • Journal of Korean Society of Environmental Engineers
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    • v.29 no.9
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    • pp.1035-1043
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    • 2007
  • A leachate containing an elevated concentration of organic and inorganic compounds has the potential to contaminate adjacent soils and groundwater as well as downgradient areas of the watershed. Moreover high-strength ammonium concentrations in leachate can be toxic to aquatic ecological systems as well as consuming dissolved oxygen, due to ammonium oxidation, and thereby causing eutrophication of the watershed. In response to these concerns landfill stabilization and leachate treatment are required to reduce contaminant loading sand minimize effects on the environment. Compared with other treatment technologies, leachate recirculation technology is most effective for the pre-treatment of leachate and the acceleration of waste stabilization processes in a landfill. However, leachate recirculation that accelerates the decomposition of readily degradable organic matter might also be generating high-strength ammonium in the leachate. Since most landfill leachate having high concentrations of nitrogen also contain insufficient quantities of the organic carbon required for complete denitrification, we combined a shortcut biological nitrogen removal (SBNR) technology in order to solve the problem associated with the inability to denitrify the oxidized ammonium due to the lack of carbon sources. The accumulation of nitrite was successfully achieved at a 0.8 ratio of $NO_2^{-}-N/NO_x-N$ in an on-site reactor of the sequencing batch reactor (SBR) type that had operated for six hours in an aeration phase. The $NO_x$-N ratio in leachate produced following SBR treatment was reduced in the landfill and the denitrification mechanism is implied sulfur-based autotrophic denitrification and/or heterotrophic denitrification. The combined leachate recirculation with SBNR proved an effective technology for landfill stabilization and nitrogen removal in leachate.

Comparison study of dermal cell toxicity and zebrafish brain toxicity by humidifier sterilizer chemicals (PHMG, PGH, CMIT/MIT) (가습기 살균제 성분(PHMG, PGH, CMIT/MIT)의 사람 피부세포 독성 및 제브라피쉬 뇌신경 독성 비교 연구)

  • Cho, Kyung-Hyun;Kim, Jae-Ryong
    • Korean Journal of Environmental Biology
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    • v.38 no.2
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    • pp.271-277
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    • 2020
  • Toxicities to many organs caused by humidifier disinfectants have been reported. Recently, humidifier disinfectants have been reported to cause cardiovascular, embryonic, and hepatic toxicities. This study was designed to investigate the toxic mechanism of humidifier disinfectants and compare toxicity in a cellular model and a zebrafish animal model. Because brain toxicity and skin toxicity have been less studied than other organs, we evaluated toxicity in a human dermal cell line and zebrafish under various concentrations of humidifier disinfectants that included polyhexamethyleneguanidine phosphate (PHMG), oligo-[2-(2-ethoxy)-ethoxyethyl-guanidinium-chloride] (PGH) and methylchloroisothiazolinone/methylisothiazolinone (CMIT/MIT). A human dermal fibroblast cell line was treated with disinfectants (0, 2, 4, 6, 8, and 16 mg L-1) to compare their cytotoxicity. The fewest PHMG-treated cells survived (up to 33%), while 49% and 40% of the PGH- and CMIT/MIT-treated cells, respectively, survived. The quantification of oxidized species in the media revealed that the PHMG-treated cells had the highest MDA content of around 28 nM, while the PGH- and CMIT/MIT-treated cells had 13 and 21 nM MDA, respectively. As for brain toxicity, treatment of the zebrafish tank water with CMIT/MIT (final 40 mg L-1) for 30 min resulted in a 17-fold higher production of reactive oxygen species (ROS) than in the control. Treatment with PGH or PHMG (final 40 mg L-1) resulted in 15- and 11-fold higher production, respectively. The humidifier disinfectants (PHMG, PGH, and CMIT/MIT) showed severe dermal cell toxicity and brain toxicity. These toxicities may be relevant factors in understanding why some children have language disorders, motor delays, and developmental delays from exposure to humidifier disinfectants.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

  • Lu, Feng-Bin;Chen, Da-Zhi;Chen, Lu;Hu, En-De;Wu, Jin-Lu;Li, Hui;Gong, Yue-Wen;Lin, Zhuo;Wang, Xiao-Dong;Li, Ji;Jin, Xiao-Ya;Xu, Lan-Man;Chen, Yong-Ping
    • Molecules and Cells
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    • v.42 no.12
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    • pp.906-918
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    • 2019
  • MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Transfer Factor of Heavy Metals from Agricultural Soil to Agricultural Products (농작물 재배지 토양 내 비소, 납 및 카드뮴의 농산물로의 전이계수 산출)

  • Kim, Ji-Young;Lee, Ji-Ho;Kunhikrishnan, Anitha;Kang, Dae-Won;Kim, Min-Ji;Yoo, Ji-Hyock;Kim, Doo Ho;Lee, Young-Ja;Kim, Won Il
    • Korean Journal of Environmental Agriculture
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    • v.31 no.4
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    • pp.300-307
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    • 2012
  • BACKGROUND: The Transfer Factor (TF) of heavy metals from soil to plant is important, because TF is an indicator of heavy metal in soils and a factor that quantifies bioavailability of heavy metals to agricultural products. This study was conducted to investigate the transfer ability of Arsenic (As), Cadmium (Cd), and Lead (Pb) from soil to agricultural products. METHODS AND RESULTS: We investigated heavy metals (As, Cd and Pb) concentrations in 9 agricultural products (rice, barely, corn, pulse, lettuce, pumpkin, apple, pear, tangerin) and soil. TF of agricultural products was evaluated based on total and HCl-extractable soil concentration of As, Cd, and Pb. Regression analysis was used to predict the relationship of total and HCl-extractable concentration with agricultural product contents of As, Cd, and Pb. The result showed that TF was investigated average 0.006~0.309 (As), 0.002~6.185 (Cd), 0.003~0.602 (Pb). The mean TF value was the highest as rice 0.309 in As, lettuce 6.185, pear 0.717, rice 0.308 in Cd, lettuce 0.602, pumpkin 0.536 in Pb which were dependent on the vegetable species and cereal is showed higher than fruit-vegetables in As. CONCLUSION(S): Soil HCl-extractable concentration of As, Cd, and Pb had the larger effects on thier contents in agricultural products than total soil concentrations. We suggests that TF are served as influential factor on the prediction of uptake. Further study for uptake and accumulation mechanism of toxic metals by agricultural products will be required to assess the human health risk and need TF of more agricultural products.

Effects of Aminotriazole on Lung Toxicity of Paraquat Intoxicated Mice (Paraquat중독에 의한 폐독성에 미치는 Aminotriazole의 영향)

  • Lee, Seung-Il;An, Gi-Wan;Chung, Choon-Hae
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.3
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    • pp.222-230
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    • 1994
  • Background: Paraquat, a widely used herbicide, is extremely toxic, causing multiple organ failure in humans. Paraquat especially leads to irreversible progressive pulmonary fibrosis, which is related to oxygen free radicals. However, its biochemical mechanism is not clear. Natural mechanisms that prevent damage from oxygen free radicals include changes in glutathione level, G6PDH, superoxide dismutase(SOD), catalase, and glutathione peroxidase. The authors think catalase is closely related to paraquat toxicity in the lungs Method: The effects of 3-amino-1,2,4-triazole(aminotriazole), a catalase inhibitor, on mice administered with paraquat were investigated. We studied the effects of aminotriazole on the survival of mice administered with paraquat, by comparing life spans between the group to which paraquat had been administered and the group to which a combination of paraquat and aminotriazole had been administered. We measured glutathion level, glucose 6-phosphate dehydrogenase(G6PDH), superoxide dismutase(SOD), catalase, and glutathione peroxidase(GPx) in the lung tissue of 4 groups of mice: the control group, group A(aminotriazole injected), group B(paraquat administered), group C(paraquat and aminotriazole administered). Results: The mortality of mice administered with paraquat which were treated with aminotriazole was significantly increased compared with those of mice not treated with aminotriazole. Glutathione level in group B was decreased by 20%, a significant decrease compared with the control group. However, this level was not changed by the administration of aminotriazole(group C). The activity of G6PDH in all groups was not significantly changed compared with the control group. The activities of SOD, catalase, and glutathione peroxidase(GPx) in the lung tissue were significantly decreased by paraquat administration(group B); catalase showed the largest decrease. Catalase and GPX were significantly decreased by aminotriazole treatment in mice administered with paraquat but change in SOD activity was not significant(group C). Conclusion: Decrease in catalase activity by paraquat suggests that paraquat toxicity in the lungs is closely related to catalase activity. Paraquat toxicity in mice is enhanced by aminotriazole administration, and its result is related to the decrease of catalase activity rather than glutathione level in the lungs. Production of hydroxyl radicals, the most reactive oxygen metabolite, is accelerated due to increased hydrogen peroxide by catalase inhibition and the lung damage probably results from nonspecific tissue injury of hydroxyl radicals.

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Inhibition of Adipocyte Differentiation by Methanol Extracts of Oenanthe javanica Seed in 3T3-L1 Preadipocytes (돌미나리씨 추출물에 의한 3T3-L1 지방전구세포의 분화 억제)

  • Ji, Hyang Hwa;Jeong, Hyun Young;Jin, Soojung;Kwon, Hyun Ju;Kim, Byung Woo
    • Journal of Life Science
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    • v.22 no.12
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    • pp.1688-1696
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    • 2012
  • Oenanthe javanica has been used as a food source and also in traditional folk medicine for its detoxifying properties and anti-microbial effects since ancient times. In this study, we evaluated the effect and mechanism of O. javanica seed methanol extract (OJSE) on adipocyte differentiation by 3T3-L1 preadipocytes. Under non-toxic conditions, OJSE treatment resulted in a dose-dependent inhibition of lipid droplet generation and triglyceride accumulation by suppressing adipocyte differentiation, which are associated with the decreased expression of key proadipogenic transcription factors including CCAAR/enhancer binding protein ${\alpha}$, ${\beta}$ ($C/EBP{\alpha}$, $C/EBP{\beta}$) and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$). OJSE also significantly inhibited proliferation and differentiation of 3T3-L1 preadipocytes through G1-phase arrest, indicating that OJSE blocked mitotic clonal expansion during adipocyte differentiation. Investigation of the alteration of G1 phase arrest-related proteins indicated a dose-dependent increase in the expression of p21 and reduction in expression of cyclin E, Cdk2, E2F-1 and phospho-Rb by OSJE. Taken together, these results suggest that OJSE inhibits adipocyte differentiation by blocking the mitotic clonal expansion, which is accompanied by preadipocyte cell cycle arrest.

Role of PKR and EGR-1 in Induction of Interleukin-S by Type B Trichothecene Mycotoxin Deoxynivalenol in the Human Intestinal Epithelial Cells (B형 트리코테센 곰팡이 독소 데옥시니발레놀에 의한 인체 장관 상피세포 염증성 인터루킨 8유도에서의 PKR과 EGR-1의 상호 역할 규명)

  • Park, Seong-Hwan;Yang, Hyun;Choi, Hye-Jin;Park, Yeong-Min;Ahn, Soon-Cheol;Kim, Kwan-Hoi;Lee, Soo-Hyung;Ahn, Jung-Hoon;Chung, Duk-Hwa;Moon, Yu-Seok
    • Journal of Life Science
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    • v.19 no.7
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    • pp.949-955
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    • 2009
  • Mucosal epithelia sense external stress signals and transmit them to the intracellular cascade responses. Ribotoxic stress-producing chemicals such as deoxynivalenol (DON) or other trichothecene mycotoxins have been linked with gastrointestinal inflammatory diseases by Fusarium-contamination. The purpose of this study was to test the hypothesis that DON evokes the epithelial sentinel signals of RNA-dependent protein kinase (PKR) and early growth response gene 1 (EGR-1), which together contribute to the pro-inflammatory cytokine interleukin 8 (IL-8) in human intestinal epithelial cells. PKR suppression by the dominant negative PKR expression attenuated DON-stimulated interleukin-8 production. Moreover, 1L-8 transcriptional activation by DON was also reduced by PKR inhibition in the human intestinal epithelial cells. Treatment with the PKR inhibitor also suppressed EGR-1 promoter activity, mRNA and protein induction, although mitogen-activated protein (MAP) kinases such as extracellular signal-regulated protein kinases (ERK) 1/2, p38, c-Jun N-terminal Kinase (INK) were little affected or even enhanced in presence of a PKR inhibitor. These patterns were also compared in the EGR-1-suppressed cells, which showed much more suppressed production of 1L-8. All things taken into consideration, DON-activated sentinel signals of EGR-1 via PKR mediated interleukin-8 production in human intestinal epithelial cells, which provide insight into the possible general mechanism associated with mucosal inflammation as an intestinal toxic insult by ribotoxic trichothecene mycotoxins.