• Molecular & Cellular Toxicology
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• 제3권2호
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• pp.107-112
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• 2007

o-Nitrotoluene is used to synthesize artificial dyes and raw materials of urethane resin. In this study, we have carried out in vitro genetic toxicity tests and microarray analysis to understand the underlying mechanisms and the mode of action of toxicity of onitrotoluene. TA1535 and TA98 cells were treated with o-nitrotoluene to test its toxicity by basic genetic toxicity test. Ames and two new in vitro micronucleus and COMET assays were applied using CHO cells and L5178Y cells, respectively. In addition, microarray analysis of differentially expressed genes in L5178Y cells in response to o-nitrotoluene was analyzed using Affymatrix genechip. The result of Ames test was that o-nitrotoluene treatment did not increase the mutations both in base substitution strain TA1535 and in frame shift TA98. o-Nitrotoluene has not increased micronuclei in CHO cells. But onitrotoluene increased DNA damage in L5178Y cell. Two-hundred two genes were initially selected as differentially expressed genes in response to o-nitrotoluene by microarray analysis and forty four genes among them were over 2 times of log fold changed. These forty four genes could be candidate biomarkers of genetic toxic action of o-nitrotoluene related to induction of mutation and/or induction of micronuclei and DNA damage. Further confirmation of these candidate markers related to the DNA damage will be useful to understand the detailed mechanism of action of o-nitrotoluene.

• Molecular & Cellular Toxicology
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• 제3권2호
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• pp.90-97
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• 2007

8-Hydroxyquinoline is used as antibacterial agent and antioxidant based on its function inducing the chelation of ferrous ion present in host resulting in production of chelated complex. This complex being transported to cell membrane of bacteria and fungi exerts antibacterial and antifungal action. In this study, we have carried out in vitro genetic toxicity tests and microarray analysis to understand the underlying mechanisms and the mode of action of toxicity of 8-hydroxyquinoline. TA1535 and TA98 cells were treated with 8-hydroxyquinoline to test its toxicity by basic genetic toxicity test, Ames and two new in vitro micronucleus and COMET assays were applied using CHO cells and L5178Y cells, respectively. In addition, microarray analysis of differentially expressed genes in L5178Y cells in response to 8-hydroxyquinoline were analyzed using Affymatrix genechip. The result of Ames test was that 8-hydroxyquinoline treatment increased the mutations in base substitution strain TA1535 and likewise, 8-hydroxyquinoline also increased mutations in frame shift TA98. 8-Hydroxyquinoline increased micronuclei in CHO cells and DNA damage in L5178Y. 8-Hdroxyquinoline resulted in positive response in all three tests showing its ability to induce not only mutation but also DNA damage. 783 Genes were initially selected as differentially expressed genes in response to 8-hydroxyquinoline by microarray analysis and 34 genes among them were over 4 times of log fold changed. These 34 genes could be candidate biomarkers of genetic toxic action of 8-hydroxyquinoline related to induction of mutation and/or induction of micronuclei and DNA damage. Further confirmation of these candidate markers related to their biological function will be useful to understand the detailed mode of action of 8-hydroxyquinoline.

• 동의생리병리학회지
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• 제24권6호
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• pp.950-955
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• 2010

In this study, we prepared CheonJeongKiBo-Dan(7 oriental medicinal plants, 7OMP: Astragalus Membranaceus root, Panax Ginseng root, Glycyrrhiza Glabra (licorice) root, Schizandra Chinensis fruit, Polygonatum Odoratum, Rehmannia Glutinosa root, Paeonia Albiflora root) by extracting them in one reactor and studied its efficacies on skin. UV irradiation has been suggested as a major cause of photoaging in skin. In order to investigate protective effects against UV-B induced cellular damage, 7OMP was extracted with 70% ethanol and dissolved in DMSO. The protective effect was detected by MTT assay, reactive oxygen species (ROS) generation, phosphorylation of ATR and p53 in human dermal fibroblast cell system after UV-B irradiation. 7OMP reduced UV-B-induced cellular damage in HDFs cells, and inhibited ROS generation. UV-B-induced toxicity accompanying ROS production and the resultant DNA damage are responsible for activation of ATR, p53 and Bad. In this study, 7OMP hampered phosphorylations of ATR and p53 in human dermal fibroblasts. Therefore, 7OMP may be protective against UV-induced skin photoaging.

• Tuberculosis and Respiratory Diseases
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• 제87권1호
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• pp.52-64
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• 2024

Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and respiratory infections injure the alveoli; the damage evoked is mostly irreversible and occasionally leads to death. Achieving a detailed understanding of the pathogenesis of these fatal respiratory diseases has been hampered by limited access to human alveolar tissue and the differences between mice and humans. Thus, the development of human alveolar organoid (AO) models that mimic in vivo physiology and pathophysiology has gained tremendous attention over the last decade. In recent years, human pluripotent stem cells (hPSCs) have been successfully employed to generate several types of organoids representing different respiratory compartments, including alveolar regions. However, despite continued advances in three-dimensional culture techniques and single-cell genomics, there is still a profound need to improve the cellular heterogeneity and maturity of AOs to recapitulate the key histological and functional features of in vivo alveolar tissue. In particular, the incorporation of immune cells such as macrophages into hPSC-AO systems is crucial for disease modeling and subsequent drug screening. In this review, we summarize current methods for differentiating alveolar epithelial cells from hPSCs followed by AO generation and their applications in disease modeling, drug testing, and toxicity evaluation. In addition, we review how current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellular heterogeneity, and maturity.

• ALGAE
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• 제29권4호
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• pp.311-319
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• 2014

The biocide sodium hypochlorite (NaOCl) is widely used for controlling algal growth, and this application can be extended to marine environments as well. This study evaluates the biocidal efficiency and cellular toxicity of NaOCl on the harmful dinoflagellate Cochlodinium polykrikoides, with emphasis on pigment production and antioxidant enzyme activity. The test organism showed dose-dependent decrease in growth rate on exposure to NaOCl, and the 72 h $EC_{50}$ was measured to be $0.584mg\;L^{-1}$. NaOCl significantly decreased pigment levels and chlorophyll autofluorescence intensity, indicating possible detrimental effects on the photosystem of C. polykrikoides. Moreover, it significantly increased the activities of antioxidant enzymes, suggesting the production of reactive oxygen species in the cells. These data indicate that NaOCl exerted deleterious effects on the photosynthetic machinery and induced oxidative damage in the dinoflagellate and this biocide could be effectively used for the control of algal blooms.

• 동의생리병리학회지
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• 제28권4호
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• pp.384-389
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• 2014

The purpose of this study is to investigate the modulatory effect of oroxylin A on hydrogen peroxide production in TM4 mouse testis sertoli cells induced by the synthetic analog of double-stranded RNA [polyinosinic-polycytidylic acid]. Hydrogen peroxide production was measured by dihydrorhodamine 123 (DHR) assay. Oroxylin A significantly inhibited the polyinosinic-polycytidylic acid (PIC)-induced production of hydrogen peroxide for 0.5, 2, 12, 18, and 24 hr incubation at the concentrations of 5, 10, 25, and $50{\mu}M$ in TM4 (P < 0.05) in dose dependent manner. These results suggest that oroxylin A has a protective effect against PIC-induced cellular toxicity with its inhibition of hydrogen peroxide production in PIC-induced sertoli cells.

• Toxicological Research
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• 제25권4호
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• pp.195-201
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• 2009

Recent publications showed that metal nanoparticles which are made from $TiO_2,\;CeO_2,\;Al_2O_3,\;CuCl_2,\;AgNO_3$ and $ZnO_2$ induced oxidative stress and pro-inflammatory effects in cultured cells and the responses seemed to be common toxic pathway of metal nanoparticles to the ultimate toxicity in animals as well as cellular level. In this study, we compared the gene expression induced by two different types of metal oxide nanoparticles, titanium dioxide nanoparticles (TNP) and cerium dioxide nanoparticles (CNP) using microarray analysis. About 50 genes including interleukin 6, interleukin 1, platelet-derived growth factor $\beta$, and leukemia inhibitory factor were induced in cultured BEAS2B cells treated with TNP 40 ppm. When we compared the induction levels of genes in TNP-treated cells to those in CNP-treated cells, the induction levels were very correlated in various gene categories (r=0.645). This may suggest a possible common toxic mechanism of metal oxide nanoparticles.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.381.3-382
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• 2002

Free radical-mediated cell damage and free radical attack on polyunsaturated fatty acids result in the formation of lipid radicals. These lipid radicals react readily with molecular oxygen to produce peroxy radicals responsible for initiating lipid peroxidation. The peroxidation of cellular membrane lipid can lead to cell necrosis and considered to be implicated in a number of pathophysiological conditions as well as in the toxicity of many xenobiotics. DPPH is known to abstract labile hydrogen and the ability to scavenge the DPPH radical is related to the inhibition of lipid peroxidation. (omitted)

• 대한의생명과학회지
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• 제7권1호
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• pp.7-15
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• 2001

Although extracorporeal circulation (ECC) has been routinely used for cardiovascular surgery, hyperoxemia during ECC may produce oxygen toxicity and cellular injury. This study was performed to investigate the clinical influences of hyperoxemic ECC during cardiovascular operation. 40 adult patients scheduled for elective cardiovascular surgery were classified into normoxemic (arterial oxygen tension: 115 mmHg, n＝20) and hyperoxemic (arterial oxygen tension: 380 mmHg, n＝20) ECC. At preoperative and postoperative period, total leukocyte and neutrophil counts, platelet counts, iron, glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine in peripheral arterial blood, malondialdehyde (MDA) and troponin-T concentration (TnT) in coronary sinus blood, pulmonary vascular resistance (PVR), and postoperative blood loss volume (BLS) were measured and compared between groups. Hyperoxemic group had postoperatively higher total leukocyte and neutrophil counts, MDA, TnT, PVR total BLS, iron, glucose, AST, ALT, BUN, and creatinine than normoxemic group (p<0.05).0 conclusion, hyperoxemic ECC results in greater inflammatory response and oxidative damaging effects on the heart lung, liver and kidney, probably being adverse to postoperative patient recovery. For reducing these deleterious effects and improving postoperative outcomes, management lowering oxygen tension during ECC is recommended.

• Journal of Microbiology and Biotechnology
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• 제9권5호
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• pp.672-674
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• 1999

Cepacidine A was first identified as a novel antifungal antibiotic which was isolated from the culture broth of Pseudomonas cepacia AF200l. It showed a potent in vitro antifungal activity against various pathogenic fungi, but did not show any activity against bacteria. Recently, the immunosuppressive action of cepacidine A was discovered using an in vitro screening system involving inhibition of the proliferation of murine lymphocytes stimulated by 2 mitogens, and also by in vivo mouse models involving inhibition of delayed type hypersensitivity and SRBC hemagglutination. Cepacidine A showed a significant activity of cellular immunosuppression (ED/sub 50/) at concentration levels of 1-3 ㎎/㎏, i.p.. Unfortunately, the delayed toxicity at a dose of above 3 ㎎/㎏ i.p. was apparent.