• Title/Summary/Keyword: BIOLOGICAL TOXICITY

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in vitro Anticancer Activity and in vivo Chronic Toxicity of Homoharringtonine (개비자나무 유효성분인 homoharringtonine의 in vitro 항암활성 및 in vivo 만성 독성)

  • Yoo, Gui-Jae;Cho, Chul-Hee;Lee, Gun-Soon;Ryoo, Zae-Young;Chae, Hee-Jeong
    • Applied Biological Chemistry
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    • v.51 no.2
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    • pp.124-128
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    • 2008
  • Cell proliferation inhibitory effects of homoharringtonine (HHT), an active drug substance in Cephalotaxus koreana, against blood cancer cell line K562 were evaluated. In addition, in vivo chronic toxicity test with mouse was carried out. When K562 cell line was treated everyday for 9, 6, 3 days, $IC_{50}$ values of HHT were determined as 0.27, 0.37, and 1.10 mM respectively. The anticancer activity of HHT was comparable to adriamycin, a known anticancer drug compound for blood cancer treatment. in vivo chronic toxicity test of the HHT, the number of red blood cell (RBC) showed no significant difference. From the analysis of the liver-functional enzymes in blood, all of liver damage related enzymes such as glutamate-oxalate-transferase (GOT), glutamate-pyruvate-transferase (GPT), cholesterol (Chol) and alkaline phosphatase (ALP) showed no significant change. However, from the histologic test, a neutrophil of the band type in liver tissue was observed.

Aluminum toxicity-induced alterations of root proteome in wheat seedlings

  • Oh, Myeong Won;Roy, Swapan Kumar;Cho, Kun;Cho, Seong-Woo;Park, Chul-Soo;Chung, Keun-Yook;Choi, Jong-Soon;Woo, Sun-Hee
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.127-127
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    • 2017
  • Aluminum is the most abundant metallic element in the Earth's crust and considered as the most limiting factor for plant productivity in acidic soils. The inhibition of root growth is recognized as the primary effect of Al toxicity. Seeds of wheat cv. Keumkang (Korean cultivar) were germinated on petridish for 5 days and then transferred hydroponic apparatus which was treated with $0{\mu}M$ $AlCl_3$ (control), $100{\mu}M$ $AlCl_3$ and $150{\mu}M$ $AlCl_3$ for 5 days. The length of roots, shoots and fresh weight of wheat seedlings were decreased under aluminum stress. The concentrations of $K^+$, $Mg^{2+}$ and $Ac^{2+}$ were decreased whereas $Al^{3+}$ and $P_2O_5{^-}$ concentration was increased under aluminum stress. Using confocal microscopy, the fluorescence intensity of aluminum was increased with morin staining. In this study, a proteome analysis was performed to identify proteins, which is responsible to aluminum stress in wheat roots. In 10-day-old seedlings, proteins were extracted from roots and separated by 2-DE, stained by CBB. Using image analysis, a total of 47 differentially expressed protein spots were selected, whereas 19 protein spots were significantly up-regulated such as s-adenosylmethionine, oxalate oxidase, malate dehydrogenase, cysteine synthase, ascorbate peroxidase and 28 protein spots were significantly down-regulated such as heat shock protein 70, o-methytransferase 4, enolase, amylogenin by aluminum stress following protein spots analyzed by LTQ-FTICR mass spectrometry. The results provide the global picture of Al toxicity-induced alterations of protein profiles in wheat roots, and identify the Al toxicity-responsive proteins related to various biological processes that may provide some novel clues about plant Al tolerance.

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Immunostimulating and Anticancer Activities of Hot Water Extract from Capsosiphon fulvescens (매생이 열수추출물의 면역 및 항암 활성)

  • Park, Hee-Yeon;Lim, Chi-Won;Kim, Yeon-Kye;Yeon, Ho-Dong;Lee, Ka-Jung
    • Applied Biological Chemistry
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    • v.49 no.4
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    • pp.343-348
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    • 2006
  • To investigate the immunostimulating and anticancer activities from hot water extract of Capsosiphon fulvescens, tumor cell toxicity, sarcoma-180 growth inhibition activity, complement system-activity, intestinal immune system and oral toxicity were performed. The extract of Capsosiphon fulvescens was prepared by hot water and precipitated by using ethanol. Partially purified extract (CFE) was obtained after dialysis and ultrafiltration. The polysaccharide compositions consisted of xylose(19.1%), fucose(15.3%), mannose(4.2%) and galactose(7.9%). The tumor cell toxicity of CFE slightly showed at high concentrations of 10-30 ${\mu}g/ml$, but inhibition ratio against mouse solid tumor was more increased for CFE of 40.1-59.4% than the control. Blood leukocyte counts increased to a maximum of 83% including liver, spleen and thymic of mouse. Immunoglobulin A binding amounts showed a high level of CFE of $2,454{\pm}113.8-2,670{\pm}133.1{\mu}g/mg$ in comparison with the control of $2,092{\pm}123.0{\mu}g/mg$. Acute toxicity of CFE was not detected at the concentration of 2,000 mg/kg in normal mouse.

Cell-Based Screen Using Amyloid Mimic β23 Expression Identifies Peucedanocoumarin III as a Novel Inhibitor of α-Synuclein and Huntingtin Aggregates

  • Ham, Sangwoo;Kim, Hyojung;Hwang, Seojin;Kang, Hyunook;Yun, Seung Pil;Kim, Sangjune;Kim, Donghoon;Kwon, Hyun Sook;Lee, Yun-Song;Cho, MyoungLae;Shin, Heung-Mook;Choi, Heejung;Chung, Ka Young;Ko, Han Seok;Lee, Gum Hwa;Lee, Yunjong
    • Molecules and Cells
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    • v.42 no.6
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    • pp.480-494
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    • 2019
  • Aggregates of disease-causing proteins dysregulate cellular functions, thereby causing neuronal cell loss in diverse neurodegenerative diseases. Although many in vitro or in vivo studies of protein aggregate inhibitors have been performed, a therapeutic strategy to control aggregate toxicity has not been earnestly pursued, partly due to the limitations of available aggregate models. In this study, we established a tetracycline (Tet)-inducible nuclear aggregate (${\beta}23$) expression model to screen potential lead compounds inhibiting ${\beta}23$-induced toxicity. High-throughput screening identified several natural compounds as nuclear ${\beta}23$ inhibitors, including peucedanocoumarin III (PCIII). Interestingly, PCIII accelerates disaggregation and proteasomal clearance of both nuclear and cytosolic ${\beta}23$ aggregates and protects SH-SY5Y cells from toxicity induced by ${\beta}23$ expression. Of translational relevance, PCIII disassembled fibrils and enhanced clearance of cytosolic and nuclear protein aggregates in cellular models of huntingtin and ${\alpha}$-synuclein aggregation. Moreover, cellular toxicity was diminished with PCIII treatment for polyglutamine (PolyQ)-huntingtin expression and ${\alpha}$-synuclein expression in conjunction with 6-hydroxydopamine (6-OHDA) treatment. Importantly, PCIII not only inhibited ${\alpha}$-synuclein aggregation but also disaggregated preformed ${\alpha}$-synuclein fibrils in vitro. Taken together, our results suggest that a Tet-Off ${\beta}23$ cell model could serve as a robust platform for screening effective lead compounds inhibiting nuclear or cytosolic protein aggregates. Brain-permeable PCIII or its derivatives could be beneficial for eliminating established protein aggregates.

Adsorption of Mn on iron minerals and calcium compounds to reduce Mn(II) toxicity (2가 망간의 독성 저감을 위해 철산화물과 칼슘화합물을 이용한 망간 흡착)

  • Hyo Kyung Jee;Jin Hee Park
    • Journal of Applied Biological Chemistry
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    • v.65 no.4
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    • pp.457-462
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    • 2022
  • Manganese (Mn) exists in various oxidation states and Mn(II) is the most mobile species of Mn, which is toxic to plants and limits their growth. Therefore, the purpose of this study was to reduce Mn toxicity by immobilizing Mn using various adsorbents including iron oxides and calcium compounds. Ferrihydrite, schwertmannite, goethite were synthesized, which was confirmed by X-ray diffraction. Hematite was purchased and used as Mn adsorbent. Calcium compounds such as CaNO3, CaSO4, and CaCO3 were used to increase pH and oxidize Mn. For Mn adsorption, Mn(II) solution was reacted with four iron oxides, CaNO3, CaSO4, and CaCO3 for 24 hours, filtered, and the remaining Mn concentrations in the solution were analyzed by inductively coupled plasma optical emission spectroscopy. The adsorption rate and adsorption isotherm were calculated. Among iron oxides, the adsorption rate was highest for hematite followed by ferrihyrite, but goethite and schwertmannite did not adsorb Mn. In the case of calcium compounds, the adsorption rate was high in the order of CaCO3>CaNO3>CaSO4. In conclusion, treatment of CaCO3 was the most effective in reducing Mn toxicity by increasing pH.

Screening of Biological Activity of Crude Drugs Using Brine Shrimp Bioassay (Brine Shrimp Bioassay를 이용한 수종생약의 생리 활성 검색)

  • Lee, Ji-Sook;Kim, Jin-Woong
    • Korean Journal of Pharmacognosy
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    • v.21 no.1
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    • pp.100-102
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    • 1990
  • Brine shrimp bioassay has been frequently utilized as a basic screening method for detecting a broad range of bioactive compounds from natural products. Each methanol, chloroform, and water extract of thirty-eight crude drugs were screened in the brine shrimp bioassay, and a number of crude drugs exhibited toxicity against brine shrimp nauplii.

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Biopesticides from Indigenous Marine-Derived Actinomycetes

  • Krishnasamy, Getha
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.163-165
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    • 1998
  • The use of synthetic pesticides in crop production, brings the possibility of a nonselective toxicity and accumulation of toxic compounds in the environment. As an alternative, bioactive compounds from actinomycetes can provide a rich source for biodegradable pesticides. A variety of biological activities such as antibacterial, antifungal, herbicidal, insecticidal and anticoccidial are associated with these microbial metabolites. Studies on the production of bioactive compounds from marine-derived actinomycetes have been very few, compared to the terrestrial actinomycetes. With their unique metabolic and physiological capabilities, the marine actinomycetes can be useful producers of novel metabolites.

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Microbial Metal Transformations

  • Gadd, Geoffrey M.
    • Journal of Microbiology
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    • v.39 no.2
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    • pp.83-88
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    • 2001
  • There is considerable interest in how microbiological processes can affect the behaviour of metal contaminants in natural and engineered environments and their potential for bioremediation. The extent to which microorganisms can affect metal contaminants is dependent on the identity and chemical form of the metal and the physical and chemical nature of the contaminated site or substance. In general terms, microbial processes which solubilize metals increase their bioavailability and potential toxicity, whereas those that immobilize them reduce bioavailability. The balance between mobilization and immobilization varies depending on the metal, the organisms, their environment and physico-chemical conditions.

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Identification and Characterization of Genes that are Induced after Cadmium Exposure

  • Lee, Mi-Ock
    • Proceedings of the PSK Conference
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    • 2003.10a
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    • pp.73-73
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    • 2003
  • The heavy metal cadmium is a xenobiotic toxicant of environmental and occupational concern and it has been classified as a human carcinogen. Inhalation of cadmium has been implicated in the development of emphysema and pulmonary fibrosis, but, the detailed mechanism by which cadmium induces adverse biological effects is not yet known. Therefore, we undertook the investigation of genes that are induced after cadmium exposure to illustrate the mechanism of cadmium toxicity. (omitted)

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Transgenic Strategy to Improve Stress Resistance of Crop Plants

  • Horvath, Gabor V.;Oberschall, Attila;Deak, Maria;Sass, Laszlo;Vass, Imre;Barna, Balazs;Kiraly, Zoltan;Hideg, Eva;Feher, Attila
    • Journal of Plant Biotechnology
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    • v.1 no.1
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    • pp.61-68
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    • 1999
  • Rapid accumulation of reactive oxygen species (ROS) and their toxic reaction products with lipids and proteins significantly contributes to the damage of crop plants under biotic and abiotic stresses. We have identified several stress activated alfalfa genes, including the gene of the alfalfa ferritin and a novel NADPH-dependent aldose/aldehyde reductase enzyme. Transgenic tobacco plants that synthesize alfalfa ferritin in vegetative tissues-either in its processed form in chloroplast or in the cytoplasmic non-processed form-retained photosynthetic function upon free radical toxicity generated by paraquat treatment and exhibited tolerance to necrotic damage caused by viral and fungal infections. We propose that by sequestering intracellular iron involved in generation of the very reactive hydroxyl radicals through a Fenton reaction, ferritin protects plant cells from oxidative damage. Our preliminary results with the other stress-inducable alfalfa gene (a NADPH-dependent aldo-keto reductase) indicate, that the encoded enzyme may play role in the stress response of the plant cells. These studies reveal new pathways in plants that can contribute to the increased stress resistance with a potential use in crop improvement.

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