• Title/Summary/Keyword: lung toxicity

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Cytotoxicity of paraquat and compensatory effects of 3-methylcholanthrene in rat lung (Paraquat의 세포독성과 흰쥐의 폐에서 3-Methylcholanthrene의 독성경감효과)

  • Rim, Yo-Sup;Kim, Doc-Soo;Han, Du-Seok;Hwang, In-Taek
    • The Korean Journal of Pesticide Science
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    • v.6 no.2
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    • pp.96-104
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    • 2002
  • This study was carried out to investigate cytotoxicity of paraquat on NIH 3T3 fibroblasts, toxicity of paraquat and compensatory effects of 3-methylcholanthrene (3-MC) on the rat lung. In order to conduct MIT [3-(4,5-Dimethylthiazol-2-yl) -2,5-diphenyl -2H-tetrazolium-bromide] and NR (Neutral red) assay, the $5.0{\times}10^4cell/ml$ of NIH 3T3 fibroblast in each well of 24 multi-dish were cultured. After 24 hours, the cells were treated with solution of paraquat (1, 25, 50 and $100{\mu}M$ respectively). After the NIH 3T3 fibroblast of all groups were cultured in same condition for 48 hours. MIT and NR assay were performed to evaluate the cytotoxicity of cell organelles. $MTT_{50}\;and\;NR_{50}$ of paraquat were $1668.97{\mu}M\;and\;1030.85{\mu}M$, respectively. These $IC_{50}$ of Paraquat were decided as a low cytotoxicity by Borenfreund and Puemer (1984). In order to observe the toxicity and compensatory effects of paraquat on the rat lung, Spraque Dawley male rats were used as experimental animals and were divided into paraquat only treated group and simultaneous application group of paraquat and 3-MC, at 30 min and 1, 3, 6, 12, 24, 48 and 96 hrs interval after each treatment. The animals were sacrificed by decapitation and their or the lungs were immediately removed, immersed in fixatives, and were processed with routine method for light microscopic study. Paraffin sections were stained with H&E and iron hematoxylin of Verhoeff. Under the light microscopy, erythrocytes were full in alveolar capillaries at 3 hrs and congested at 24 hrs after paraquat administration. The great alveolar cells (Type II cell) were increased and mitosis of great alveolar were observed in interalveolar septa. Many lymphocytes, macrophages and polymorphonuclear (PMN) cells were observed in connective tissue surrounding lung tissue and germinal center in lymph follicles of terminal bronchiole. Alveolar macrophages were increased in interalveolar septa and alveoli at 48 hrs. And observed many alveolar macrophages at 96 hrs. In iron hematoxylin stain of Verhoeff, Collagen fiber were increased in respiratory bronchiole, interalveolar septa and alveoli and breath of alveoli, and alveolar pore were broaden. But, in paraquat plus 3-MC treated group, morphological changes were mild in lung tissue. These results indicate that 3-MC has a compensatory effects against toxicity of paraquat by conjugation with oxygen.

Gemcitabine Plus Vinorelbine as Second-line Chemotherapy of the Patients of Previously Treated Non-small Cell lung Cancer: Phase II Trial (비소세포 폐암 환자의 이차 치료로서 Gemcitabine과 Vinorelbine 혼합 요법의 효과)

  • Jang, Pil Soon;Kang, Hyun Mo;Lee, Jeong Eun;Kwon, Seon Jung;An, Jin Young;Lee, Yun Sun;Jeong, Sung Soo;Kim, Ju Ock;Kim, Sun Young
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.4
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    • pp.344-351
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    • 2005
  • Background : Both gemcitabine and vinorelbine are effective anticancer drugs with mild toxicity on non-small cell lung cancer, and monotherapy of these drugs are effective as a second-line chemotherapy. The aim of this trial was to assess the response and toxicity of a combination of gemcitabine and vinorelbine in patients of previously treated for non-small cell lung cancer. Materials and Methods : 24 patients, initial stage III A/B,IV and previously treated with platinium and taxane based regimens, were enrolled from June 2000 to March 2004. The regimens consisted of vinorelbine $25mg/m^2$ followed by an infusion of gemcitabine $1000mg/m^2$ on day 1 and day 8 every three weeks. This course was repeated more than twice. Results : Twenty-four patients were analyzed for the response, survival rate, and toxicities. The overall response was 17% with a complete remission rate of 4%. The median time-to progression (TTP) was 3.1 months (95%, CI 1-10months), and the survival time was 8.2 months (95%, CI 1-23 months). The grade 3/4 toxicities encountered were neutropenia (12.5%), anemia (0%), thrombocytopenia (0%). Non-hematological 3/4 toxicities were not observed. Conclusion : A combination of gemcitabine and vinorelbine in patients previously treated for non-small cell lung cancer provides a relatively good response rate, and a low toxicity profile. However, further study will be needed to confirm its effectiveness.

Toxico-pathological Study p,p-DDE After Experimental Aerosol Exposed to ICR Mouse (환경호르몬인 p,p-DDE의 흡입 시 ICR 마우스의 폐에 미치는 독성병리학적 연구)

  • Choi Hae-Yun;Jung Tae-Young;Ku Sae-Kwang;Yang Hee-Bog;Lee Hyeung-Sik
    • Toxicological Research
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    • v.21 no.2
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    • pp.151-160
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    • 2005
  • In order to monitor the histological and general profiles of lung after direct expose of p,p-DDE, 1, 5 and 10 mg/ml of p,p-DDE were sprayed to male ICR mouse, and seven days after exposure, changes of body weight, lung weight, clinical signs, histological profiles of lung and total WBC in blood were investigated with changes of total cell number and their differential count in bronchoalveolar lavage fluid (BALF). In the present study, a significant and dosage-dependent decrease of body weight was detected in p,p-DDE exposed groups and body weight gains during observational periods (7 days) were also significantly and dosage-dependently decreased in p,p-DDE exposed groups compared to that of vehicle control group. In addition general depression signs were detected in all p,p-DDE exposed groups with dosage-dependent manners, and lung weights were also increased in p,p-DDE exposed groups. Congestion, hemorrhage and severe exudate were observed in the lung of p,p-DDE exposed groups with sarcomatous changes and these signs were also showed by dosage-dependent manners. In addition, foreign body pneumonia signs were observed in the lung of p,p-DDE exposed groups in histological levels. The percentage of ALSA (Area of luminal surface of alveoli) was also significantly and dosage-dependently decreased in p,p-DDE exposed groups and total blood WBC and BALF cell numbers were significantly and dosage-dependently increased in p,p­DDE exposed groups compared to that of vehicle control group and increase percentage of neutrophil, eosinophil, and lymphocyte in BALF were monitored in p,p-DDE exposed groups compared to that of vehicle control group. In conclusion, severe allergic response and/or foreign body pneumonitic changes were induced by direct exposure of p,p-DDE containing beverage. So it is considered that strong and powerful regulation was need to control production of residence of environmental pollutant especially to p,p-DDE.

Affecting Factors of Lung Disease and Classification of Exposure Rating of Applicants for Injuries from Humidifier Disinfectants (가습기살균제 피해신청자들의 노출등급 분류 및 폐질환 발생 영향요인 분석)

  • Gihong, Min;Junghyun, Shin;Eun-Kyung, Jo;Dayoung, Jeong;Jiyoon, Ryu;Dongjun, Kim;Jaemin, Woo;Sungho, Bae;Jihun, Shin;Seula, Lee;Yoon-Hyeong, Choi;Wonho, Yang
    • Journal of Environmental Health Sciences
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    • v.48 no.6
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    • pp.324-330
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    • 2022
  • Background: Lung injuries due to exposure to humidifier disinfectants (HDs) were reported in 2011 in South Korea. As a result of the government's epidemiological investigation and toxicity test study, it was found that HDs caused health damage such as lung disease. Objectives: The purpose of this study was to classify HD exposure ratings and analyze the affecting factors that could identify the relationship with lung disease. Methods: Exposure assessment for HDs was conducted using a questionnaire during face-to-face interviews with the applicants. Ratings of high exposure (Class 1) and low exposure (Class 2) were cross-tabulated with clinical ratings (acceptable and unacceptable). Logistic regression analysis was carried out by setting the clinical rating of lung disease as a dependent variable and the socio-demographic and exposure characteristics obtained through the questionnaire as independent variables. Results: The concentration in air of polyhexamethylene guanidine (PHMG) was 71.96±107.47 ㎍/m3, and the exposure concentration was 15.21±23.28 ㎍/m3 . The exposure rating was overestimated with 97.1% of affected subjects having high exposure using margin of exposure (MOE), but only 9.9% matching the clinical class. In the overestimated group, it could be explained by the fact that the exposure time was long and the subjects had already recovered from damage symptoms. As a result of logistic regression analysis, ten variables were found to be significant influencing factors. Conclusions: A new exposure rating could be calculated based on the MOE, and factors affecting lung disease could be estimated through comparative evaluation with the clinical rating.

Genetic Toxicity Study of YH1715 Series, Antifungal Agents (YH1715계열 항진균제의 유전독성평가)

  • 하광원;오혜영;박장환;허옥순;손수정;한의식;이종영;김소희;강희일
    • Environmental Mutagens and Carcinogens
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    • v.18 no.2
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    • pp.93-97
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    • 1998
  • The results of chromosome aberration test in mammalian cells in culture (Chinese hamster lung fibroblast cells) showed no induction of structural and numerical aberrations by antifungal agents of YH1715 series regardless of metabolic activation. While positive control group (mitomycin C and benzo(a)pyrene) showed structural chromosome aberrations of 37% and 23%, respectively. The in vivo induction of micronuclei was measured in polychromatic erythrocytes in bone marrow of male ddY mouse given YH1715R and YH1729R at 1, 0.5, 0.25 g/kg by p.o. once. After 24 hours, animals were sacrificed and evaluated 40 the incidence of micronucleated polychromatic erythrocytes in whole erythrocytes. Although a positive response for induction of micronuclei in animals treated with mitomycin C demonstrated the sensitivity of the test system for detection of a chemical clastogen, YH1715R did not induce micronuclei in bone marrow of ddY male mice but induced cytotoxicity to bone marrow cells at the highest concentration (1 g/kg, p〈0.05), and YH1729R induced micronuclei in bone marrow of ddY male mice dose dependently (p<0.05) but did not induce cytotoxicity to bone marrow cells.

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The Study of Literature Review on Poisoning and the Pragmatic Significance of the Processing Method of Armeniacae Amarum Semen to use in oriental medical prescription (방제활용을 위한 행인(杏仁)의 포제 및 독성의 문헌적 고찰)

  • Kim, Se-Ran;Lee, Jin-Won;Lim, So-Yeon;Kim, Jong-Dae
    • Herbal Formula Science
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    • v.19 no.2
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    • pp.151-160
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    • 2011
  • Objectives : The purpose of this study was to investigate Armeniacae Amarum Semen of poison and the Pragmatic significance of the processing method. Methods : We researched several books dealing with Armeniacae Amarum Semen of poison and the Pragmatic significance of the processing method. Results & Conclusions : Armeniacae Amarum Semen is sweet, bitter, warm and harmful in nature. It is known as moistening the lung to arrest cough, moistening the colon, to move the bowels and promoting digestion and curing dog bites. Armeniacae Amarum Semen has toxicity, decreasing toxicity of Armeniacae Amarum Semen is boiling, peeling or roasting. If Armeniacae Amarum Semen has two seeds in one apricot or has six-floral leaf, do not used for medicinal purposes.

Health Effects of Chronic Arsenic Exposure

  • Hong, Young-Seoub;Song, Ki-Hoon;Chung, Jin-Yong
    • Journal of Preventive Medicine and Public Health
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    • v.47 no.5
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    • pp.245-252
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    • 2014
  • Arsenic is a unique element with distinct physical characteristics and toxicity whose importance in public health is well recognized. The toxicity of arsenic varies across its different forms. While the carcinogenicity of arsenic has been confirmed, the mechanisms behind the diseases occurring after acute or chronic exposure to arsenic are not well understood. Inorganic arsenic has been confirmed as a human carcinogen that can induce skin, lung, and bladder cancer. There are also reports of its significant association to liver, prostate, and bladder cancer. Recent studies have also suggested a relationship with diabetes, neurological effects, cardiac disorders, and reproductive organs, but further studies are required to confirm these associations. The majority of research to date has examined cancer incidence after a high exposure to high concentrations of arsenic. However, numerous studies have reported various health effects caused by chronic exposure to low concentrations of arsenic. An assessment of the health effects to arsenic exposure has never been performed in the South Korean population; thus, objective estimates of exposure levels are needed. Data should be collected on the biological exposure level for the total arsenic concentration, and individual arsenic concentration by species. In South Korea, we believe that biological exposure assessment should be the first step, followed by regular health effect assessments.

Toxicity and Carcinogenicity of Dichlorodiphenyltrichloroethane (DDT)

  • Harada, Takanori;Takeda, Makio;Kojima, Sayuri;Tomiyama, Naruto
    • Toxicological Research
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    • v.32 no.1
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    • pp.21-33
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    • 2016
  • Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p'-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT.

Differential Gene Expression Profiling in Human Promyelocytic Leukemia Cells Treated with Benzene and Ethylbenzene

  • Sarma, Sailendra Nath;Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.4 no.4
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    • pp.267-277
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    • 2008
  • Benzene and ethylbenzene (BE), the volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Chronic exposure of benzene is responsible for myeloid leukemia and also ethylbenzene is also recognized as a possible carcinogen. To evaluate the BE effect on human, whole human genome 35 K oligonucleotide microarray were screened for the identification of the differential expression profiling. We identified 280 up-regulated and 201 down-regulated genes changed by more than 1.5 fold by BE exposure. Functional analysis was carried out by using DAVID bioinformatics software. Clustering of these differentially expressed genes were associated with immune response, cytokine-cytokine receptor interaction, toll-like signaling pathway, small cell lung cancer, immune response, apoptosis, p53 signaling pathway and MAPKKK cascade possibly constituting alternative or subordinate pathways of hematotoxicity and immune toxicity. Gene ontology analysis methods including biological process, cellular components, molecular function and KEGG pathway thus provide a fundamental basis of the molecular pathways through BEs exposure in human lymphoma cells. This may provides a valuable information to do further analysis to explore the mechanism of BE induced hematotoxicity.

Antimycobacterial Activity and Cytotoxicity of Flavonoids from the Flowers of Chromolaena odorata

  • Suksamrarn, Apichart;Chotipong, Apinya;Suavansri, Tananit;Boongird, Somnuk;Timsuksai, Puntip;Vimuttipong, Saovaluk;Chuaynugul, Aporn
    • Archives of Pharmacal Research
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    • v.27 no.5
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    • pp.507-511
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    • 2004
  • From the flowers of Chromolaena odorata (Eupatorium odoratum) four flavanones, isosakuranetin (5,7-dihydroxy-4'-methoxyflavanone) (1), persicogenin (5,3'-dihydroxy-7,4'-dimethoxyflavanone) (2), 5,6,7,4'-tetramethoxyflavanone (3) and 4'-hydroxy-5,6,7-trimethoxyfla-vanone (4), two chalcones, 2'-hydroxy-4,4',5',6'-tetramethoxychalcone (5) and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (6), and two flavones, acacetin (5,7-dihydroxy-4'-methoxyflavone) (7) and luteolin (5,7,3',4'-tetrahydroxyflavone) (8) were isolated and identified. Compound 1 exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis with the MIC value of 174.8 $\mu$M, whereas compounds 4,7, and 8 exhibited weak activity with the MIC values of 606.0, 704.2 and 699.3 $\mu$M respectively. Compound 7 showed moderate cytotoxicity against human small cell lung cancer (NCI-H187) cells with the MIC value of 24.6 $\mu$M, whereas compound 8 exhibited moderate toxicity against NCI-H187 cells and week toxicity against human breast cancer (BC) cells with the MIC values of 19.2 and 38.4 $\mu$M respectively.