• Title/Summary/Keyword: In vitro toxicology

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Estrogenic Activity Assessment of Alkylphenolic chemicals using in vitro assays : I. E-Screen Assay

  • Park, Hyo-Joung;Lee, Ho-Sa;Na, Jin-Gyun;Ryu, Jae-Chun
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2001.05a
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    • pp.125-125
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    • 2001
  • It has been hypothesized that environmental estrogens may play roles in the increasing incidence of breast and testicular cancers and another problems of the reproductive systems. Alkylphenols which are widely used as plastic additives and surfactants have been shown to induce estrogenic responses. The E-screen assay was developed to assess the estrogenedity of environmental chemicals using the profiferation effect of estrogens on their target cells as an end point. (omitted)

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Synthesis and Antioxidant Properties of Some Novel Benzimidazole Derivatives on Lipid Peroxidation in the Rat Liver

  • Canan Kus;Gulgun, Ayhan-Kilcigil;Eke, Benay-Can;Mumtaz Iscan
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.156-163
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    • 2004
  • Some benzimidazole derivatives namely 1-[(substituted thiocarbamoylhydrazine carbonyl) methyl]-2-phenyl-1 H-benzimidazoles (1a-13a), N-[(2-phenylbenzimidazol-1-yl methyl)-[1,3,4]-thiadiazole-2-yl]-substituted phenyl amines (1b-13b) and 5-(2-phenyl benzimidazol-1-yl-methyl)-4-substituted phenyl-4H-1,2,4-triazole-3-thiones (1c-13c) were synthesized, and their in vitro effects on the rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels were determined. The most active compound 10a caused an 84% inhibition of LP at $10^{-3}$ M, which is better than that of butylated hydroxytoluene (BHT) (65%).

Biochemical and Pharmacological Properties of a New Proton Pump Inhibitor, 2-Amino-4,5-dihydropyrido[1,2-a]thiazolo [5,4-g] benzimidazole (YJA20379-5)

  • Sohn, Sang-Kwon;Chang, Man-Sik;Chung, Young-Kuk;Kim, Kyu-Bong;Woo, Tae-Wook;Kim, Sung-Gyu;Choi, Wahn-Soo
    • Archives of Pharmacal Research
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    • v.21 no.3
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    • pp.241-247
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    • 1998
  • This study was designed to determine biochemical and pharmacological properties of a newly synthesized benzimidazole derivative, 2-amino-4, 5-dihydropyrido [1, 2-a] thiazolo [5, 4-g] benzimidazole (YJA20379-5) in vitro and in vivo. In the leaky membrane vesicles of pig gastric mucosa, YJA20379-5 inhibited the $K^+$-stimulated $H^+$, $K^+$-ATPase activity in a concentration- and time-dependent manner, with $IC_{50}$ values being $43{\mu}\textrm{M}$ and $43{\mu}\textrm{M}$ at pH 6.4 and 7.4, respectively. YJA20379-5, given intraduodenally, had a potent inhibitory effect on the gastric acid secretion in pylorus-ligated rats. The $ED_{50}$ value for acid secretion was 15.4 mg/kg. YJA20379-5, administered orally, also suppressed gastric damages induced by water-immersion stress, indomethacin and ethanol, and duodenal damage induced by mepirizole in rats; the $ED_{50}$ values were 17.6, 4.7, 3.0 and 18.7 mg/kg, respectively. Furthermore, repeated oral administration of YJA20379-5 accelerated the spontaneous healing of acetic acid-induced gastric ulcers in rats. It is concluded that the a-ntisecretory activity of YJA20379-5 appears to be associated with inhibition of $H^+$, $K^+$-ATPase, while its antigastric and antiduodenal lesion activities are primarily related to the antisecretory effect.

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Free Radical Toxicology and Cancer Chemoprevention

  • Lin, Jen-Kun
    • Toxicological Research
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    • v.17
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    • pp.83-88
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    • 2001
  • Most reactive oxygen species (ROS) are free radicals and implicated in the development of a number of disease processes including artherosclerosis, neurodegenerative disorders, aging and cancer. ROS are byproducts of a number of in vivo metabolic processes and are formed deliberately as part of nor-mal inflammatory response. On the other hand, ROS are generated either as by products of oxygen reduction during xenobiotic metabolism or are liberated as the result of the futile redox cycling of the chemical agents including several chemical carcinogens. A better understanding of the mechanisms of free radical toxicity may yield valuable clue to risks associated with chemical exposures that leading to the development of chronic diseases including cancer. The molecular biology of ROS-mediated alterations in gene expression, signal transduction and carcinognesis is one of the important subjects in free radical toxicology. Epidemiological studies suggest that high intake of vegetables and fruits are associated with the low incidence of human cancer. Many phytopolyphenols such as tea polyphenols, curcumin, resveratrol, apigenin, genistein and other flavonoids have been shown to be cancer chemopreventive agents. Most of these compounds are strong antioxidant and ROS scavengers in vitro and effective inducers of antioxidant enzymes such as superoxide dismutatse, catalase and glutathione peroxidase in vivo. Several cellular transducers namely receptor tyrosine kinase, protein kinase C, MAPK, PI3K, c-jun, c-fos, c-myc, NFkB, IkB kinase, iNOS, COX-2, Bcl-2, Bax, etc have been shown to be actively modulated by phyto-polyphenols. Recent development in free radical toxicology have provided strong basis for understanding the action mechanisms of cancer chemoprevention.

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Study on Genotoxicity of Crocin, a Component of Gardenia Fruit, in Bacterial and Mammalian Cell Systems

  • Choi, Hae-Yeon;Kim, Youn-Jung;Jeon, Hee-Kyung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.4 no.4
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    • pp.285-292
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    • 2008
  • Crocin is one of the major components of gardenia fruit and saffron which are widely used as natural food colorants and as traditional Chinese medicines. However, the genotoxicity data on crocin are not sufficient for safety evaluation. The purpose of this study was the examination of the genotoxicity on crocin from gardenia yellow in bacterial and mammalian cells, using various genotoxic battery testing assays and the influence of crocin on methyl methanesulfonate (MMS) and ${H_2}{O_2}$-induced DNA damage in vitro, using single cell gel electrophoresis (comet) assay. From results, no considerable mutagenicity and clastogenicity were seen in bacteria and mammalian cells treated with crocin, by Ames test, chromosomal aberration assay, ${tk}^{+/-}$ gene forward mutation assay and comet assay. And, post-treatment with crocin significantly suppressed ${H_2}{O_2}$-induced DNA damage in a dose-dependent manner. In conclusion, the findings of the present study and other previous observations indicate that crocin has no genotoxic potential. And it showed that crocin clearly repressed the genotoxic potency of ${H_2}{O_2}$. These results suggest that anti-oxidative effects of crocin may be involved in the protective effects of DNA damage.

Toxicological Characterization of Phthalic Acid

  • Bang, Du-Yeon;Lee, In-Kyung;Lee, Byung-Mu
    • Toxicological Research
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    • v.27 no.4
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    • pp.191-203
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    • 2011
  • There has been growing concern about the toxicity of phthalate esters. Phthalate esters are being used widely for the production of perfume, nail varnish, hairsprays and other personal/cosmetic uses. Recently, exposure to phthalates has been assessed by analyzing urine for their metabolites. The parent phthalate is rapidly metabolized to its monoester (the active metabolite) and also glucuronidated, then excreted. The objective of this study is to evaluate the toxicity of phthalic acid (PA), which is the final common metabolic form of phthalic acid esters (PAEs). The individual PA isomers are extensively employed in the synthesis of synthetic agents, for example isophthalic acid (IPA), and terephthalic acid (TPA), which have very broad applications in the preparation of phthalate ester plasticizers and components of polyester fiber, film and fabricated items. There is a broad potential for exposure by industrial workers during the manufacturing process and by the general public (via vehicle exhausts, consumer products, etc). This review suggests that PA shows in vitro and in vivo toxicity (mutagenicity, developmental toxicity, reproductive toxicity, etc.). In addition, PA seems to be a useful biomarker for multiple exposure to PAEs in humans.

Humidifier disinfectant disaster: what is known and what needs to be clarified

  • Kim, Sungkyoon;Paek, Domyung
    • Environmental Analysis Health and Toxicology
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    • v.31
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    • pp.25.1-25.9
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    • 2016
  • Objectives After the initial investigations by the Korea Centers for Disease Control in 2011, over 1000 suspicious cases of humidifier disinfectant (HD) victims were subsequently reported by 2015, and numbers are still increasing dramatically in 2016 in the midst of the prosecutors' office investigation. This study attempts to summarize the current understandings of the related health effects of HD based upon a systemic review of published epidemiologic studies and toxicology investigations. Methods Published studies of HDs were searched through PubMed and TOXLINE under the search words 'humidifier disinfectant,' and related reports were identified from the references and published report list of regulatory agencies including the Korean National Institute of Environmental Research, US Environmental Protection Agency, and EU European Chemicals Agency. Results Case reports and epidemiologic studies have reported the clinical features of severe forms of HD lung damage, together with epidemiologic findings of seasonal occurrence and demographic variations, including the heightened susceptibility of young children. Toxicological studies have reported inhalation toxicities together with positive findings of in vitro genotoxicity studies. Conclusions This study examined unsolved issues based on cases of upper respiratory diseases and diseases of other organs, including cancers, among suspected victims of HDs. These issues should be clarified in future research for the management and prevention of health effects from HDs and chemicals of other related household products.

[Retracted] Novel Genotoxic Strategies for Efficiently Detect Chemicals' Carcinogenicity ([논문 철회] 노동자 건강보호를 위한 최신 유전독성학 연구전략)

  • Rim, Kyung-Taek
    • Journal of Environmental Health Sciences
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    • v.44 no.1
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    • pp.31-43
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    • 2018
  • Objectives: Effective genetic toxicology and molecular biology research techniques and strategies that are highly correlated with the carcinogenic inhalation toxicity test and related research are required. The aim of this study was to maximize the utilization of chemical substances to prevent workers' occupational diseases. Methods: We surveyed the literature, domestic and international references, and the status of relevant domestic and foreign professional organizations. Expert advisory opinions were reflected, and experts were consulted by participating in domestic and overseas academic conferences. Results: The current status of domestic and international genotoxic toxicity evaluation was examined through various documents from related organizations. Cell models for in vitro lung toxicology were investigated and summarized, and the human resources and performance results of genetic toxicity studies and pilot projects were compared and analyzed by holding an advisory meeting. We examined domestic and international genotoxicity guidelines and investigated new test methods for the development of genotoxicity and carcinogenicity. Ultimately, we described long-term future predictions, including the implementation of our researchers' recommendations and occupational genetic toxicology forecasts for future worker health protection. Conclusions: This research project aims to establish current genetic toxicology and molecular biology research techniques and strategies that can maximize the linkage with the carcinogenic inhalation toxicity test and research in the future. We expanded the study of genetic toxicity and establish a foundation forgenetic toxicity in accordance with research trends in Korea and abroad.

Scavenging Effects of Flavonoids on Paraquat Induced Pulmonary Toxicity (Paraquat 유도 폐독성에 대한 Flavonoid류의 독성경감 효과)

  • 최병기;조내규
    • Environmental Analysis Health and Toxicology
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    • v.10 no.3_4
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    • pp.29-40
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    • 1995
  • To investigate and evaluate the scavenging and antioxidative effects of various ftavonoids on paraquat induced pulmonary toxicity, in vivo and vitro tests of eight flavonoids(catechin, epicatechin, flayone, chrysin, apigenin, quercetin, morin and biochanin A) were carried out. In vitro test, inhibitory and antioxidative effects of lipoxygenase dependent lipidperoxidation, NADPH dependent cytochrome p-450 reductase to liver and lung microsome and superoxide anion production in rat peritoneal exudated macrophage were studied. In vivo test, biochemical parameters and cell population in bronchoalveolar lavage fluid(BALF) in mouse and rats after administration of paraquat and flavonoids were tested. The results are summerized as follows; 1. All flavonoids tested inhibited on NADPH dependent cytochrome p-450 reductase in liver and lung microsome. 2. All flavonoids tested showed the inhibitory effects on the superoxide anion production in rat peritoneal exudated macropharge. 3. Lactate dehydrogenase, acid phosphatase and total protein in BALF of mouse which increased by the administration of paraquat, decreased significantly by catechin, chrysin, morin and biochanin A. 4. Numbers of alveolar macropharge and PMN in BALF of rats which increased by the administration of paraquat decreased by all the tested flavonoids. Therefore, all flavonoids tested showed the useful compounds for scavenger and antioxidant on paraquat induced pulmonary toxicity.

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Effects of Organic Solvents on Mucus Penetration Distance, Motility and Survival Rate of Human Sperm in vitro (수종의 유기용제가 사람 정자의 점액 침투능, 운동성과 생존율에 미치는 영향)

  • Yoo Dong-Chul;Choi Dal-Woong
    • Environmental Analysis Health and Toxicology
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    • v.19 no.2
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    • pp.177-182
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    • 2004
  • Alcohol consumption and exposure to endocrine disruptors and industrial solvents have been implicated in impaired spermatogenesis, increase in the incidence of malformed sperm and decrease in the percentage of moving sperm. The aim of this study was to determine and compare the direct effects of some organic solvents(bisphenol A; BPA, dibutyl phthalate; DBP, formaldehyde; HCHO, dimethylsulphoxide; DMSO, ethanol) on mucus penetration distance, motility and survival rate of human sperm in vitro. Semen samples from 3 health subjects were prepared using swim-up method and 0.0005-0.5% organic solvents were added to the test medium. BPA, DBP, HCHO and DMSO produced significant decreases in the motility and survival rate with a different potency. The most potent inhibition of mucus penetration distance, motility and survival rate was observed after exposure to HCHO. A concentration of 0.0005% HCHO significantly inhibited sperm motility. When ethanol m.: added directly to sperm, at concentrations equivalent to that in serum after heavy drinking, these damaging effects were lowest compared with other solvents. Present study shows that each compound has different toxic potency to human sperm and we need special caution for the use of HCHO.