• Title/Summary/Keyword: human toxicity

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Gene Expression Analysis of So Called Asian Dust Extracts in Human Acute Myeloid Leukemia Cells

  • Choi, You-Jin;Yin, Hu-Quan;Park, Eun-Jung;Park, Kwang-Sik;Kim, Dae-Seon;Lee, Byung-Hoon
    • Toxicological Research
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    • v.26 no.1
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    • pp.21-28
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    • 2010
  • As the frequency and the intensity of so called Asian dust (AD) events have increased, public concerns about the adverse health effects has spiked sharply over the last two decades. Despite the recent reports on the correlation between AD events and the risk for cardiovascular and respiratory disease, the nature of the toxicity and the degree of the risk are yet largely unknown. In the present study, we investigated the effects of the dichloromethane extract of AD (AD-X) and that of urban dust (NAD-X) collected during a non-AD period on gene expression in HL-60 cells using Illumina Sentrix HumanRef-8 Expression BeadChips. Global changes in gene expression were analyzed after 24 h of incubation with 50 or 100 ${\mu}g$/ml AD-X and NAD-X. By one-way analysis of variance (p < 0.05) and Benjamini-Hochberg multiple testing correction for false discovery rate of the results, 573 and 297 genes were identified as AD-X- and NAD-X-responsive, respectively. The genes were classified into three groups by Venn diagram analysis of their expression profile, i.e., 290 AD-X-specific, 14 NAD-X-specific, and 283 overlapping genes. Quantitative realtime PCR confirmed the changes in the expression levels of the selected genes. The expression patterns of five genes, namely SORL1, RABEPK, DDIT4, AZU1, and NUDT1 differed significantly between the two groups. Following rigorous validation process, these genes may provide information in developing biomarker for AD exposure.

Synergistic Effect of Ethaselen and Selenite Treatment against A549 Human Non-small Cell Lung Cancer Cells

  • Xu, Wei;Ma, Wei-Wei;Zeng, Hui-Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7129-7135
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    • 2014
  • Background: In this study, we aimed to evaluate the growth inhibitory effect of the combination of ethaselen (BBSKE) and low fixed dose of selenite against A549 human non-small cell lung cancer cells in vitro. Materials and Methods: Growth inhibitory effects against A549 cells were determined by SRB assay. Combination index (CI) values were calculated based on Chou-Talalay median-effect analyses. Dose reduction index (DRI) values were applied to calculate dose reduction of selenite. Contents of free thiols and GSH were determined by DTNB assay and intracellular ROS levels by DCFH-DA fluorescence labeling. Results: Compared with BBSKE or selenite single treatment, the combined application of ethaselen and a low fixed dose of selenite shortened the onset time of sodium selenite, reduced $IC_{50}$ values, and increased the maximum inhibition rates, suggesting a possible molecular mechanism of the synergism. Obvious synergistic effects were observed after different times of combination treatment, especially after 24 h. Compared with selenite single treatment, dosage of selenite could be remarkably reduced in combination therapy to gain the same inhibitory effect on cell proliferation. Compared with BBSKE single treatment, the content of free thiols and GSH were significantly reduced and ROS levels greatly elevated in the combination group. For the combination treatment, cell viability increased as greater concentrations of GSH were added. Conclusions: All these results indicate that the combination treatment of BBSKE and selenite showed synergism to inhibit A549 cell proliferation in vitro, and also reduced the selenite dosage to mitigate its toxicity which is very meaningful for combination chemotherapy of lung cancer. The synergism was probably caused by the accelerated exhaustion of intracellular reductive substances, such as free thiols and GSH, which ultimately leads to enhanced oxidative stress and apoptosis.

The effect of the cytotoxicity of sodium lauryl sulfate containing toothpaste on HaCaT and NIH-3T3 cells (구강세치제에 함유된 SLS(Sodium lauryl Sulfate)가 HaCaT 세포와 NIH-3T3 세포에 미치는 독성 효과)

  • Park, Sang-Rye;Kim, Young-Min;Choi, Byul-Bora;Kim, Ji-Young
    • Journal of Korean society of Dental Hygiene
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    • v.15 no.4
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    • pp.719-725
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    • 2015
  • Objectives: The purpose of this study was to determine the toxic effects of sodium lauryl sulfate(SLS) in human keratinocyte HaCaT cells and mouse fibroblast NIH-3T3 cells. Methods: The effect of sodium lauryl sulfate(SLS) cell viability and proliferation were determined by WST-1 assay and changes shape of nucleus were evaluated by Hoechst staining under fluorescence microscopy. Additionally, observation of cell morphological changes under light microscopy. Results: SLS induced cytotoxicity and a marked apoptosis in both HaCaT and NIH-3T3 cell lines. With the result of the WST-1 assay, SLS induced the cytotoxicity of 0.005% and 0.0075%, 0.01% SLS for 24 h after HaCaT and NIH-3T3 cells in time and dose-dependent manner(p<0.005). SLS inhibited cell growth and caused apoptosis as evidenced by nuclear fragmentation and condensation. Thus, determination of the morphological changes to define apoptosis was visualized using inverted phase contrast microscopy. Conclusions: SLS had toxicity of the human keratinocyte cells and mouse fibroblast cells and this study will provide the basic data for the development of proper SLS concentration in dentifrice.

Wild Mushrooms: A Potential Source of Nutritional and Antioxidant Attributes with Acceptable Toxicity

  • Sharif, Sumaira;Shahid, Muhammad;Mushtaq, Muhammad;Akram, Sumia;Rashid, Ayoub
    • Preventive Nutrition and Food Science
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    • v.22 no.2
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    • pp.124-130
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    • 2017
  • This paper describes in detail proximate composition, nutritional profile, phytochemical constituents, antioxidant activities, antimicrobial potential, and antihemolytic activity (towards human erythrocytes) of various fractions of wild Ganoderma lucidum. Proximate analysis established that wild G. lucidum comprises about $87.02{\pm}5.45%$ of moisture, and the remaining part is a rich source of proteins ($8.59{\pm}0.37%$), crude fiber ($54.21{\pm}1.2%$), and carbohydrate (35.16%) with smaller fat content (3.33 %). Similarly, phytochemical screening revealed the presence of flavonoids ($217.51{\pm}0.30mg/g$), ascorbic acid ($116{\pm}7.32mg/g$), phenolics ($360.72{\pm}34.07mg/g$), ${\beta}$-carotenes ($0.42{\pm}0.04{\mu}g/g$), and lycopene ($0.05{\pm}0.00{\mu}g/g$). Extracts of wild G. lucidum in various solvents provided first line protection against Escherichia coli and Pasteurella multocida in the order of ethyl acetate> ethanol> methanol> n-hexane> water. Furthermore, aqueous and methanolic extracts of wild G. lucidum were found to be safe towards human erythrocytes. Overall, wild mushroom (G. lucidum) was found to be a good source of dietary supplements, antimicrobial and antioxidant agents in the pursuance of its commercial utilization in food and pharmaceutical industries.

Anti Proliferative Properties of Melissa officinalis in Different Human Cancer Cells

  • Jahanban-Esfahlan, Akram;Modaeinama, Sina;Abasi, Mozhgan;Abbasi, Mehran Mesgari;Jahanban-Esfahlan, Rana
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5703-5707
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    • 2015
  • Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of their antioxidative properties. Melissa officinalis L. (MO), an aromatic and medicinal plant, is well known in thios context. However, toxicity against cancer cells has not been fully studied. Here, we investigated the selective anticancer effects of an MO extract (MOE) in different human cancer cells. Materials and Methods: a hydro-alcoholic extract of MO was prepared and total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. MTT assays were used to evaluate cytotoxicity of different doses of MOE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) towards A549 (lung non small cell cancer cells), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all cancer cells, MOE reduced the cell viability to values below 33%, even at the lowest doses. In all cases, $IC_{50}$ values were below $5{\mu}g/ml$. The mean growth inhibition was 73.1%, 86.7%, 79.9% and 77.8% in SKOV3, MCF-7 and PC-3 and A549 cells, respectively. Conclusions: Our results indicate that a hydro-alcoholic extract of MO possess a high potency to inhibit proliferation of different tumor cells in a dose independent manner, suggesting that an optimal biological dose is more important than a maximally tolerated one. Moreover, the antiprolifreative effect of MO seems to be tumor type specific, as hormone dependant cancers were more sensitive to antitumoral effects of MOE.

Initial Risk Assessment System of Pesticides - A case study of captan, paraquat dichloride, and glyphosate - (농약의 초기위해성평가체계에 관한 연구 - Captan, Paraquat dichloride, Glyphosate에 대한 Case study -)

  • Lee, Yong-Ju;Kim, Kyun;Kim, Yong-Hwa
    • The Korean Journal of Pesticide Science
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    • v.9 no.3
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    • pp.214-220
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    • 2005
  • Initial Risk assessments using physicochemical properties and acute toxicity are conducted to provide information for managers to decide the potential adverse effects and played as a tool for decision-making in development of new substances. In this study, we built initial risk assessment framework and carried out human and ecology initial risk assessment for three different pesticides of captan, glyphosate, and paraquat dichloride to confirm our framework. Two water estimation models of GENEEC (GENeric Estimated Environmental Concentration) and FOCUS (FOrum for the Co-ordination of pesticide models and their USe) were employed for pesticides exposure assessment. Application for paraquat dichloride and glyphosate uses shows very low human and ecology risk. On the other hand, high acute ecological risk was observed from the application for captan. These results showed good agreements with the U.S. EPA RED (Reregistration Eligibility Decision) reports verifying the framework of this study.

Heavy Metal Risk Management: Case Analysis

  • Kim, Ji-Ae;Lee, Seung-Ha;Choi, Seung-Hyun;Jung, Ki-Kyung;Park, Mi-Sun;Jeong, Ji-Yoon;Hwang, Myung-Sil;Yoon, Hae-Jung;Choi, Dal-Woong
    • Toxicological Research
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    • v.28 no.3
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    • pp.143-149
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    • 2012
  • To prepare measures for practical policy utilization and the control of heavy metals, hazard control related institutions by country, present states of control by country, and present states of control by heavy metals were examined. Hazard control cases by heavy metals in various countries were compared and analyzed. In certain countries (e.g., the U.S., the U.K., and Japan), hazardous substances found in foods (e.g., arsenic, lead, cadmium, and mercury) are controlled. In addition, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) recommends calculating the provisional tolerable weekly intake (PTWI) of individual heavy metals instead of the acceptable daily intake (ADI) to compare their pollution levels considering their toxicity accumulated in the human body. In Korea, exposure assessments have been conducted, and in other countries, hazardous substances are controlled by various governing bodies. As such, in Korea and other countries, diverse food heavy metal monitoring and human body exposure assessments are conducted, and reducing measures are prepared accordingly. To reduce the danger of hazardous substances, many countries provide leaflets and guidelines, develop hazardous heavy metal intake recommendations, and take necessary actions. Hazard control case analyses can assist in securing consumer safety by establishing systematic and reliable hazard control methods.

Isolation of Urease Inhibitory Compounds from Arecae Semen (빈랑자 (Arecae Semen)로부터 Urease 억제 활성 물질의 분리)

  • Ryu, Jei-Man;Jang, Hwan-Bong;Rho, Yang-Kook;Oh, Seong-Jun;Lee, Hyun-Yong;Leem, Moon-Jeong
    • Korean Journal of Pharmacognosy
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    • v.36 no.1 s.140
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    • pp.56-59
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    • 2005
  • Urease plays an important role in the urea metabolism and the effect of urease activity on human and environment is enormous. For instance, urease acts as a virulence factor of the urinary and gastrointestinal tracts infections in human and animal, being involved in kidney stone formation, catheter encrusatation, pyelonephritis, ammonia encephalopathy, hepatic coma, and urinary tract infections. Widespread urease activity in soil induces a plant damage due to ammonia toxicity and pH increase. Therefore, urease activity regulation through urease inhibitors would lead to an enhanced efficiency of urea nitrogen uptake in plants and to the improved therapeutic strategies for ureolytic bacterial infections. To search for new inhibitory compounds on urease activity from herbs, MeOH extracts of herbs were screened. Among of them, the MeOH extracts of Areca catechu exhibited an excellent inhibitory effect on urease activity. Two compounds were isolated from the ethyl acetate fraction by the activity guided fractionation. Their chemical structures were identified as (+)-catechin(compound I) and allantoin(compound II) by spectroscopic evidence, respectively. Compound I showed a stronger inhibitory effect on urease activity than compound II.

Effects of Dried Gentiana scabra Rhizomes and Roots on the Intestinal Transit Rate of Mice with Experimental Gastrointestinal Motility Dysfunctions (용담 열수 추출물이 위장관 운동 기능 저해 상황에서 위장관 이송률에 미치는 영향)

  • Lee, Hyun-Tai
    • Journal of Life Science
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    • v.29 no.12
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    • pp.1345-1350
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    • 2019
  • Our recent study has revealed that in vivo intestinal transit rate (ITR) in normal mice was significantly increased by the administration of an aqueous extract of dried Gentiana scabra rhizomes and roots (GS-W) in a dose-dependent manner. Following on from our previous study, the effect of GS-W on ITR was measured in mice with experimentally induced gastrointestinal motility dysfunctions (GMDs) in the present study. GS-W showed no significant acute toxicity even at an oral dose of 5 g/kg to mice. ITR was significantly retarded in the GMD mice compared with that in normal mice, and this retardation was significantly recovered by the oral administration of GS-W in a dose-dependent manner. Furthermore, the ITR value of GS-W at a dose of 1 g/kg appeared to be higher than that of cisapride, which was predominantly prescribed for human patients with various GMDs in the late 1900s but was withdrawn from the market in 2000 due to its fatal side effects. The current results suggest that GS-W is a potential substitute for cisapride to prevent or alleviate human GMDs.

Neurotoxin-Induced Pathway Perturbation in Human Neuroblastoma SH-EP Cells

  • Do, Jin Hwan
    • Molecules and Cells
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    • v.37 no.9
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    • pp.672-684
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    • 2014
  • The exact causes of cell death in Parkinson's disease (PD) remain unknown despite extensive studies on PD.The identification of signaling and metabolic pathways involved in PD might provide insight into the molecular mechanisms underlying PD. The neurotoxin 1-methyl-4-phenylpyridinium ($MPP^+$) induces cellular changes characteristic of PD, and $MPP^+$-based models have been extensively used for PD studies. In this study, pathways that were significantly perturbed in $MPP^+$-treated human neuroblastoma SH-EP cells were identified from genome-wide gene expression data for five time points (1.5, 3, 9, 12, and 24 h) after treatment. The mitogen-activated protein kinase (MAPK) signaling pathway and endoplasmic reticulum (ER) protein processing pathway showed significant perturbation at all time points. Perturbation of each of these pathways resulted in the common outcome of upregulation of DNA-damage-inducible transcript 3 (DDIT3). Genes involved in ER protein processing pathway included ubiquitin ligase complex genes and ER-associated degradation (ERAD)-related genes. Additionally, overexpression of DDIT3 might induce oxidative stress via glutathione depletion as a result of overexpression of CHAC1. This study suggests that upregulation of DDIT3 caused by perturbation of the MAPK signaling pathway and ER protein processing pathway might play a key role in $MPP^+$-induced neuronal cell death. Moreover, the toxicity signal of $MPP^+$ resulting from mitochondrial dysfunction through inhibition of complex I of the electron transport chain might feed back to the mitochondria via ER stress. This positive feedback could contribute to amplification of the death signal induced by $MPP^+$.