• Title/Summary/Keyword: cellular toxicity

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A Study on Gamma ray effects on Stress Response and Cellular Toxicity using Bacterial Cells

  • Min, Ji-Ho;Lee, Hyeon-Ju;Lee, Chang-U;Gu, Man-Bok
    • 한국생물공학회:학술대회논문집
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    • 2000.11a
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    • pp.187-190
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    • 2000
  • Effects of gamma ionizing radiation on recombinant Escherichia coli cells containing stress promoters, recA, fabA, grpE, or katG, fused to luxCDABE originated from Vibrio fischeri were characterized by monitoring transcriptional responses reflected by bioluminescent output. Quantification of gamma-ray intensity may be possible using the recA and fabA promoter fusion since a linear enhancement of bioluminescence emission with increasing gamma-ray intensity was observed. Other strains sensitive to either oxidative stress (DPD2511, katG::luxCDABE) or protein-damaging stress (TV1061, grpE::luxCDABE) were also irradiated by gamma-rays, and resulted in no noticeable bioluminescent output while DPD2794 with recA promoter and DPD2540 with fabA promoter irradiated by the same intensities of gamma-rays gave a significant bioluminescent output. This indicates that the main stresses in the recombinant bacteria caused by ionizing radiation are DNA and membrane-damage, not protein- or oxidative-damage. In addition, in this study, to investigate the relationship between the radiation dose rate and bacterial responses, two recombinant Escherichia coli strains, DPD2794 and GC2, containing lac promoter fused to luxCDABE originating from Photorhapdus luminescences, were used for detecting DNA damage and cellular toxicity under various radiation dose rates. Throughout this study, it was found that these bacteria showed quantitative stress responses to DNA damage and general toxicity caused by gamma rays, depending on the radiation dose rates, indicating that the bacterial stress responses and general toxicity were seriously influenced according to radiation dose rates.

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Protective effects of mealworm (Tenebrio molitor) extract on N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced cellular toxicity in SH-SY5Y neuroblastoma cells (SH-SY5Y 인간 신경모세포종 세포에서 MPTP 유발 세포 독성에 대한 거저리(Tenebrio molitor) 추출물의 보호효과)

  • In Ho Jo;Yoo Ji Kim;Seon Tae Kim
    • Journal of The Korean Society of Clinical Toxicology
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    • v.21 no.2
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    • pp.81-91
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    • 2023
  • Purpose: Edible insect extracts have been used as an alternative source for medicinal supplements due to their significant antioxidative and anti-inflammatory activity. Recent studies have reported that anti-microbial peptides from insects have neuroprotective effects on dopamine toxins. The purpose of this study was to investigate the protective functions of mealworm (Tenebrio molitor) extract (MWE) on N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced cellular toxicity in SH-SY5Y neuroblastoma cells. Methods: Cellular toxicity induced by the MPTP toxin and the impact of MWE on cell survival were analyzed using MTT assays. DAPI staining was performed to observe apoptotic phenomena caused by MPTP. Changes in caspase-3 activity and protein expression were observed using enzyme activity assays and western blot assays, respectively. Results: MWE exerted significant antioxidant activity, which was measured by both DPPH and ABTS radical assays, with a dose-dependent relationship. Furthermore, MWE resulted in cellular proliferation in SHSY5Y cells in a dose-dependent manner. Furthermore, MWE pretreatment significantly inhibited MPTP-induced cytotoxicity, with a dose-dependent relationship. The morphological characteristics of apoptosis and increased reactive oxygen species induced by MPTP were also significantly reduced by MWE pretreatment. Conclusion: MWE treatment significantly attenuated MPTP-induced changes in the levels of proteins associated with apoptosis, such as caspase-3 and PARP. These findings suggest that MWE exerts neuroprotective effects on human neuroblastoma SH-SY5Y cells subject to MPTP-induced dopaminergic neurodegeneration.

Identification of Hepatotoxicity Related Genes Induced by Hexachlorobenzne (HCB) in Human Hepatocellular Carcinoma (HepG2) Cells

  • Kim, Youn-Jung;Choi, Han-Saem;Song, Mee;Song, Mi-Kyung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.5 no.3
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    • pp.179-186
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    • 2009
  • Hexachlorobenzene (HCB) is a bioaccumulative, persistent, and toxic pollutant. HCB is one of the 12 priority of Persistent Organic Pollutants (POPs) intended for global action by the United Nations Environment Program (UNEP) Governing Council. POPs are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes. Some of HCB is ubiquitous in air, water, soil, and biological matrices, as well as in major environmental compartments. HCB has effects on various organs such as thyroid, bone, skin, kidneys and blood cells and especially, revealed strong toxicity to liver. In this study, we identified genes related to hepatotoxiciy induced by HCB in human hepatocellular carcinoma (HepG2) cells using microarray and gene ontology (GO) analysis. Through microarray analysis, we identified 96 up- and 617 down-regulated genes changed by more than 1.5-fold by HCB. And after GO analysis, we determined several key pathways which known as related to hepatotoxicity such as metabolism of xenobiotics by cytochrome P450, complement and coagulation cascades, and tight junction. Thus, our present study suggests that genes expressed by HCB may provide a clue for hepatotoxic mechanism of HCB and gene expression profiling by toxicogenomic analysis also affords promising opportunities to reveal potential new mechanistic markers of toxicity.

Effect of Copper on Marine Microalga Tetraselmis suecica and its Influence on Intra- and Extracellular Iron and Zinc Content

  • Kumar, K. Suresh;Shin, Kyung-Hoon
    • Korean Journal of Ecology and Environment
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    • v.50 no.1
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    • pp.16-28
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    • 2017
  • In an aquatic environment, toxicity of metals to organisms depends on external factors (type of metal, exposure concentration and duration, environmental parameters, and water quality) and intracellular processes(metal-binding sites and detoxification). Toxicity of copper(Cu) on the marine microalga Tetraselmis suecica was investigated in this study. Dose-dependent (Cu concentration dependent) inhibition of growth and cell division, as well as, variation of intra- and extra-cellular Cu, Fe and Zn content was observed. T. suecica was sensitive to Cu; the 96 h $EC_{50}$ (concentration to inhibit growth-rate by 50%) of growth rate (${\mu}$) ($21.73{\mu}M\;L^{-1}$), cell division $day^{-1}$ ($18.39{\mu}M\;L^{-1}$), and cells $mL^{-1}$ ($13.25{\mu}M\;L^{-1}$) demonstrate the toxicity of Cu on this microalga. High intra-($19.86Pg\;cell^{-1}$) and extra-cellular($54.73Pg\;cell^{-1}$) Cu concentrations were recorded, on exposure to 24.3 and $72.9{\mu}M\;L^{-1}$ of Cu.

Synthesis, Characterization, and the Influence of Functionalized Multi-Walled Carbon Nanotubes with Creatinine and 2-Aminobenzophenone on the Gastric Cancer Cells

  • Tahermansouri, Hasan;Aryanfar, Yaser;Biazar, Esmaeil
    • Bulletin of the Korean Chemical Society
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    • v.34 no.1
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    • pp.149-153
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    • 2013
  • The chemical functionalization of carboxylated multi-walled carbon nanotubes (MWCNT-COOH) by creatinine (MWCNT-Amide) and latter modification with 2-aminobenzophenone for producing 1-methyl-9-phenyl-1H-imidazo[4,5-b]quinolin-2-amine (MWCNT-quino) have been investigated. All products were characterized by Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscope, elemental analysis, thermogravimetric analysis, derivative thermogravimetric and cellular investigations. The interesting point is that MWCNT-quino can be homogeneously dispersed in dimethylformamide and to some extent in ethyl alcohol without sonication. Also, MTT assay was used to examine the behavior of cell proliferation after 48 h of cell culture experiments. Cellular results showed high toxicity of MWCNT-quino on the cancer cells. These functionalizations have been chosen due to active sites of carbonyl and methylene groups in MWCNT-Amide and the creating quinoline derivative on the MWCNTs for future application.

Naringenin Exerts Cytoprotective Effect Against Paraquat-Induced Toxicity in Human Bronchial Epithelial BEAS-2B Cells Through NRF2 Activation

  • Podder, Biswajit;Song, Ho-Yeon;Kim, Yong-Sik
    • Journal of Microbiology and Biotechnology
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    • v.24 no.5
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    • pp.605-613
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    • 2014
  • We have previously shown that paraquat (PQ)-induced oxidative stress causes dramatic damage in various human cell lines. Naringenin (NG) is an active flavanone, which has been reported to have beneficial bioactivities, including antioxidative, anti-inflammatory, and antitumorigenic activities, with a relatively low toxicity to normal cells. In this study, we intended to assess the cytoprotective effect of NG against PQ-induced toxicity in the human bronchial epithelial BEAS-2B cell line. Co-treatment with NG in PQ-treated BEAS-2B cells can reduce PQ-induced cellular toxicity. NG can also decrease the generation of intracellular ROS caused by PQ treatment. We also observed that treatment with NG in PQ-exposed BEAS-2B cells can significantly induce the expression of antioxidant-related genes, including GPX2, GPX3, GPX5, and GPX7. NG co-treatment can also activate the NRF2 transcription factor and promote its nuclear translocation. In addition, NG co-treatment can induce the expression of NRF2-downstream target genes such as that of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). A small interfering RNA study revealed that the knockdown of NRF2 can abrogate NG-mediated protection of the cells from PQ-induced cellular toxicity. We propose that NG effectively alleviates PQ-induced cytotoxicity in human bronchial epithelial BEAS-2B cells through the NRF2-regulated antioxidant defense pathway, and NG might be a good therapeutic candidate molecule in oxidative stress-related diseases.

The effects of water extract from Dictamnus dasycarpus Turcz on Hepatocellular Damage in vitro (백선 추출물의 간세포 손상에 대한 연구)

  • Ha, Hun-Yong
    • The Korea Journal of Herbology
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    • v.29 no.5
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    • pp.91-95
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    • 2014
  • Objectives : This study was carried out to evaluate whether the water extract from cause the cellular damage in HepG2 cell line. It was reported that Dictamnus dasycarpus Turcz(DDT) intake induce poisoning symptoms in human population. These symptoms was closely related to liver toxicity, however, mechanisms for liver toxicity caused by DDT have not been elucidated exactly. Here, hepatotoxicity caused by DDT was evaluated using HepG2 cell line. Methods : Water extract of DDT was treated into HepG2 cell with various doses such as 0, 0.1, 0.5, 1.0 and $5.0mg/m{\ell}$. In order to cell viability, both MTT and LDH assay were carried out. Also, apoptosis array kit was used to identify whether cell death caused by DDT is due to apoptosis or not. In addition, reactive oxygen species (ROS) was measured after treatment of water extract. Results : We found out significant changes in the apoptosis related factors of hepatocyte. The cell viability of HepG2 treated with DDT water extract was decreased in dose-dependent. Also most of the apoptosis related factors were significantly increased. We found out that Caspase 3, Cytochrome C and ROS had increased in dose-dependent. In addition, other apoptosis related factors Bcl 2 and Bax, which were also constant changes. However, there was no significance. Conclusions : These results suggest that water soluble extract of DDT is expected to have oral toxicity, including hepatocellular damage Therefore, it is suggested that DDT could cause various side effects and toxicity of clinical conditions.

Comparison of cytotoxicities and wound healing effects of diquafosol tetrasodium and hyaluronic acid on human corneal epithelial cells

  • Lee, Jong Heon;Lee, Jong Soo;Kim, Sujin;Lee, Ji Eun
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.2
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    • pp.189-195
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    • 2017
  • This study aimed to compare the cellular toxicities of three clinically used dry eye treatments; 3% diquafosol tetrasodium and hyaluronic acid at 0.3 and 0.18%. A methyl thiazolyltetrazoiun (MTT)-based calorimetric assay was used to assess cellular proliferation and a lactate dehydrogenase (LDH) leakage assay to assess cytotoxicity, using Human corneal epithelial cells (HCECs) exposed to 3% diquafosol tetrasodium, 0.3% hyaluronic acid (HA), or 0.18% HA or 1, 6 or 24 h. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy, and wound widths were measured 24 h after confluent HCECs were scratched. Diquafosol had a significant, time-dependent, inhibitory effect on HCEC proliferation and cytotoxicity. HCECs treated with diquafosol detached more from the bottoms of dishes and damaged cells showed degenerative changes, such as, reduced numbers of microvilli, vacuole formation, and chromatin of the nuclear remnant condensed along the nuclear periphery. All significantly stimulated reepithelialization of HCECs scratched, which were less observed in diquafosol. Therefore, epithelial toxicity should be considered after long-term usage of diquafosol and in overdose cases, especially in dry eye patients with pre-existing punctated epithelial erosion.

Gene Expression Profiling of Human Bronchial Epithelial (BEAS-2B) Cells Treated with Nitrofurantoin, a Pulmonary Toxicant

  • Kim, Youn-Jung;Song, Mee;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.3 no.4
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    • pp.222-230
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    • 2007
  • Some drugs may be limited in their clinical application due to their propensity towards their adverse effects. Toxicogenomic technology represents a useful approach for evaluating the toxic properties of new drug candidates early in the drug discovery process. Nitrofurantoin (NF) is clinical chemotherapeutic agent and antimicrobial and used to treatment of urinary tract infections. However, NF has been shown to result in pulmonary toxic effects. In this research, we revealed the changing expression gene profiles in BEAS-2B, human bronchial epithelial cell line, exposed to NF by using human oligonucleotide chip. Through the clustering analysis of gene expression profiles, we identified 136 up-regulated genes and 379 down-regulated genes changed by more than 2-fold by NF. This study identifies several interesting targets and functions in relation to NF-induced toxicity through a gene ontology analysis method including biological process, cellular components, molecular function and KEGG pathway.