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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Journal DOI :
The Korean Society of Toxicology
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Volume & Issues
Volume 30, Issue 4 - Dec 2014
Volume 30, Issue 3 - Sep 2014
Volume 30, Issue 2 - Jun 2014
Volume 30, Issue 1 - Mar 2014
Selecting the target year
Human Tumor Xenograft Models for Preclinical Assessment of Anticancer Drug Development
Jung, Joohee ;
Toxicological Research, volume 30, issue 1, 2014, Pages 1~5
DOI : 10.5487/TR.2014.30.1.001
Xenograft models of human cancer play an important role in the screening and evaluation of candidates for new anticancer agents. The models, which are derived from human tumor cell lines and are classified according to the transplant site, such as ectopic xenograft and orthotopic xenograft, are still utilized to evaluate therapeutic efficacy and toxicity. The metastasis model is modified for the evaluation and prediction of cancer progression. Recently, animal models are made from patient-derived tumor tissue. The patient-derived tumor xenograft models with physiological characters similar to those of patients have been established for personalized medicine. In the discovery of anticancer drugs, standard animal models save time and money and provide evidence to support clinical trials. The current strategy for using xenograft models as an informative tool is introduced.
A Rapid Method for Estimating the Levels of Urinary Thiobarbituric Acid Reactive Substances for Environmental Epidemiologic Survey
Kil, Han-Na ; Eom, Sang-Yong ; Park, Jung-Duck ; Kawamoto, Toshihiro ; Kim, Yong-Dae ; Kim, Heon ;
Toxicological Research, volume 30, issue 1, 2014, Pages 7~11
DOI : 10.5487/TR.2014.30.1.007
Malondialdehyde (MDA), used as an oxidative stress marker, is commonly assayed by measuring the thiobarbituric acid reactive substances (TBARS) using HPLC, as an indicator of the MDA concentration. Since the HPLC method, though highly specific, is time-consuming and expensive, usually it is not suitable for the rapid test in large-scale environmental epidemiologic surveys. The purpose of this study is to develop a simple and rapid method for estimating TBARS levels by using a multiple regression equation that includes TBARS levels measured with a microplate reader as an independent variable. Twelve hour urine samples were obtained from 715 subjects. The concentration of TBARS was measured at three different wavelengths (fluorescence:
530 nm and
515 nm and
553 nm; and absorbance: 532 nm) using microplate reader as well as HPLC. 500 samples were used to develop a regression equation, and the remaining 215 samples were used to evaluate the validity of the regression analysis. The induced multiple regression equation is as follows: TBARS level (
) = -0.282 + 1.830
(TBARS level measured with a microplate reader at the fluorescence wavelengths
530 nm and
(TBARS level measured with a microplate reader at the fluorescence wavelengths
515 nm and
) + 0.035
(TBARS level measured with a microplate reader at the absorbance wavelength 532 nm,
). The estimated TBARS levels showed a better correlation with, and are closer to, the corresponding TBARS levels measured by HPLC compared to the values obtained by the microplate method. The TBARS estimation method reported here is simple and rapid, and that is generally in concordance with HPLC measurements. This method might be a useful tool for monitoring of urinary TBARS level in environmental epidemiologic surveys with large sample sizes.
Inhallation of e-Cigarette Cartridge Solution Aggravates Allergen-induced Airway Inflammation and Hyper-responsiveness in Mice
Lim, Heung Bin ; Kim, Seung Hyung ;
Toxicological Research, volume 30, issue 1, 2014, Pages 13~18
DOI : 10.5487/TR.2014.30.1.013
Electronic cigarettes (e-cigarettes) are becoming increasingly popular worldwide and their cellular effects warrant further evaluation. In this study, we investigated the effects of an e-cigarette cartridge solution on allergen related asthmatic airway inflammation (AI) and airway hyperresponsiveness (AHR), when it is delivered by intratracheal route in mice. Asthmatic AI and AHR were induced by systemic sensitization to ovalbumin (OVA) followed by intratracheal, intraperitoneal, and aerosol allergen challenges in BALB/c mice. The cartridge solution of e-cigarette (containing 16 mg/ml nicotine) was diluted 50 times and
of the diluted solution was intratracheally instilled to OVA-sensitized (OVA-S) mice two times a week for 10 weeks. Long-term e-cigarette inhalation elicited no remarkable changes in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase enzymes in serum, however, increased infiltration of inflammatory cells including eosinophils, into airways from blood, aggravated the asthmatic AI and AHR, and stimulated the production of cytokines such as interleukin (IL)-4, IL-5 and IL-13, and OVA-specific IgE production. Our data suggest that the inhalation of e-cigarette solutions can function as an important factor to exacerbate the allergy-induced asthma symptoms. Further studies are needed to address the effects of e-cigarette solutions on human health.
Licochalcone Suppresses LXRα-Induced Hepatic Lipogenic Gene Expression through AMPK/Sirt1 Pathway Activation
Han, Jae Yun ; Park, Sun Hee ; Yang, Ji Hye ; Kim, Mi Gwang ; Cho, Seung Sik ; Yoon, Goo ; Cheon, Seung Hoon ; Ki, Sung Hwan ;
Toxicological Research, volume 30, issue 1, 2014, Pages 19~25
DOI : 10.5487/TR.2014.30.1.019
Licochalcone (LC), a major phenolic retrochalcone from licorice, has anti-inflammatory activity. This study investigated the effects of licochalcone A (LCA) and licochalcone E (LCE) on Liver X receptor-
)-mediated lipogenic gene expression and the molecular mechanisms underlying those effects. LCA and LCE antagonized the ability of
agonists (T0901317 or GW3965) to increase sterol regulatory element binding protein-1c (SREBP-1c) expression and thereby inhibited target gene expression (e.g., FAS and ACC) in HepG2 cells. Moreover, treatment with LCA and LCE impaired
-induced CYP7A1-LXRE-luciferase (CYP7A1) transactivation. The AMPK-Sirt1 signaling pathway is an important regulator of energy metabolism and, therefore, a potential therapeutic target for metabolic diseases, including hepatic steatosis. We found here that LCE increased AMPK phosphorylation and Sirt1 expression. We conclude that LC inhibits SREBP-1c-mediated hepatic lipogenesis via activation of the AMPK/Sirt1 signaling pathway.
A Probiotic Preparation Duolac-Gold Ameliorates Dextran Sulphate Sodium-induced Mouse Colitis by Downregulating the Expression of IL-6
Yoon, Hyunho ; Yoon, Yeo-Sang ; Kim, Min-Soo ; Chung, Myung-Jun ; Yum, Do-Young ;
Toxicological Research, volume 30, issue 1, 2014, Pages 27~32
DOI : 10.5487/TR.2014.30.1.027
Probiotics are live microorganisms that confer a health benefit on the host. Duolac-Gold is a mixture of seven probiotic bacteria containing three species of Bifidobacteria, two species of Lactobacillus, and Streptococcus thermophilus. The aim of this study was to assess the anti-inflammatory effects of Duolac-Gold in an inflammatory bowel disease (IBD) mouse model. IBD was induced by administering 1.5% dextran sulfate sodium (DSS) for 10 days. After induction of DSS-induced colitis, Duolac-Gold was orally administered at three different concentrations. Interestingly, Duolac-Gold treatment accelerated IBD healing, and anti-inflammatory activity was assessed by weight loss, length of the colon, and a microscopic damage score by histology. The expression of inflammatory related cytokines was measured in colon tissues and serum. Of these cytokines, the expression of interleukin-6 decreased remarkably after Duolac-Gold treatment. Taken together, these results suggest that Duolac-Gold treatment is effective in IBD healing by regulating IL-6.
Expression and Characterization of Truncated Recombinant Human Cytochrome P450 2J2
Park, Hyoung-Goo ; Lim, Young-Ran ; Han, Songhee ; Kim, Donghak ;
Toxicological Research, volume 30, issue 1, 2014, Pages 33~38
DOI : 10.5487/TR.2014.30.1.033
The human cytochrome P450 2J2 catalyzes an epoxygenase reaction to oxidize various fatty acids including arachidonic acid. In this study, three recombinant enzyme constructs of P450 2J2 were heterologously expressed in Escherichia coli and their P450 proteins were successfully purified using a
-NTA affinity column. Deletion of 34 amino acid residues in N-terminus of P450 2J2 enzyme (2J2-D) produced the soluble enzyme located in the cytosolic fraction. The enzymatic analysis of this truncated protein indicated the typical spectral characteristics and functional properties of P450 2J2 enzyme. P450 2J2-D enzymes from soluble fraction catalyzed the oxidation reaction of terfenadine to the hydroxylated product. However, P450 2J2-D enzymes from membrane fraction did not support the P450 oxidation reaction although it displayed the characteristic CO-binding spectrum of P450. Our finding of these features in the N-terminal modified P450 2J2 enzyme could help understand the biological functions and the metabolic roles of P450 2J2 enzyme and make the crystallographic analysis of the P450 2J2 structure feasible for future studies.
Association between Urinary Bisphenol A and Waist Circumference in Korean Adults
Ko, Ahra ; Hwang, Myung-Sil ; Park, Jae-Hong ; Kang, Hui-Seung ; Lee, Hee-Seok ; Hong, Jin-Hwan ;
Toxicological Research, volume 30, issue 1, 2014, Pages 39~44
DOI : 10.5487/TR.2014.30.1.039
Bisphenol A (BPA) is widely used in the production of polycarbonate plastics, epoxy resins, and food and beverage containers. In the present study, we aimed to investigate the relationship between urinary concentrations of BPA and waist circumference in Korean adults. A total of 1,030 Korean adults (mean age,
years) were enrolled in the study on the integrated exposure to hazardous materials for safety control, conducted by the Ministry of Food and Drug Safety from 2010 to 2012. Abdominal obesity was defined as having a waist circumference of at least 90 cm and 85 cm for men and women, respectively. The participants were divided into 4 groups according to the urinary BPA concentration quartile. Waist circumference was significantly higher among subjects with a urinary BPA concentration in the highest quartile relative to those in the lowest quartile (p = 0.0071). Linear regression analysis revealed a significant positive association between urinary BPA concentrations and body mass index, body fat, after adjusting for potential confounders. Moreover, subjects with urinary BPA concentrations in the fourth quartile were more likely to be obese compared to those with urinary BPA concentrations in the first quartile (odds ratio, 1.938; 95% CI: 1.314~2.857; p for trend = 0.0106). These findings provide evidence for a positive association between urinary BPA concentration and waist circumference in Korean adults.
Inhibitory Activities of Palmatine from Coptis chinensis Against Helicobactor pylori and Gastric Damage
Jung, Joohee ; Choi, Jae Sue ; Jeong, Choon-Sik ;
Toxicological Research, volume 30, issue 1, 2014, Pages 45~48
DOI : 10.5487/TR.2014.30.1.045
Helicobacter pylori (H. pylori) is the most important factor of gastric disease in clinical practice. Moreover, smoking, stress and a poor diet may be additive factors for gastric damage. With these factors, increasing infection of H. pylori triggers gastritis, gastric ulcers and gastric cancer. To develop a new protective agent, we are concerned with plant-derived extract. The extract of Coptis chinensis (C. chinensis) and its constituents were investigated to assess their protective activities against gastric damage. The C. chinensis extract showed a scavenging effect against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals, inhibition of H. pylori colonization and antiulcerogenic activities in rat. In particular, palmatine derived from C. chinensis was found to be the novel protective agent. It is better than the C. chinensis extract, berberine, a well-known constituent of C. chinensis. We suggest that palmatine from the root cortex of C. chinensis may be a good candidate for the development of new pharmaceuticals to prevent gastric disease.
Hepatoprotective Effect of Aged Black Garlic Extract in Rodents
Shin, Jung Hyu ; Lee, Chang Woo ; Oh, Soo Jin ; Yun, Jieun ; Kang, Moo Rim ; Han, Sang-Bae ; Park, Heungsik ; Jung, Jae Chul ; Chung, Yoon Hoo ; Kang, Jong Soon ;
Toxicological Research, volume 30, issue 1, 2014, Pages 49~54
DOI : 10.5487/TR.2014.30.1.049
In this study, we investigated the hepatoprotective effects of aged black garlic (ABG) in rodent models of liver injury. ABG inhibited carbon tetrachloride-induced elevation of aspartate transaminase (AST) and alanine transaminase (ALT), which are markers of hepatocellular damage, in SD rats. D-galactosamine-induced hepatocellular damage was also suppressed by ABG treatment. However, ABG does not affect the elevation of alkaline phosphatase (ALP), a marker of hepatobilliary damage, in rats treated with carbon tetrachloride or D-galactosamine. We also examined the effect of ABG on high-fat diet (HFD)-induced fatty liver and subsequent liver damage. ABG had no significant effect on body weight increase and plasma lipid profile in HFD-fed mice. However, HFD-induced increase in AST and ALT, but not ALP, was significantly suppressed by ABG treatment. These results demonstrate that ABG has hepatoprotective effects and suggest that ABG supplementation might be a good adjuvant therapy for the management of liver injury.
Studies on the Toxicity and Distribution of Indium Compounds According to Particle Size in Sprague-Dawley Rats
Lim, Cheol Hong ; Han, Jeong-Hee ; Cho, Hae-Won ; Kang, Mingu ;
Toxicological Research, volume 30, issue 1, 2014, Pages 55~63
DOI : 10.5487/TR.2014.30.1.055
Objectives: The use of indium compounds, especially those of small size, for the production of semiconductors, liquid-crystal panels, etc., has increased recently. However, the role of particle size or the chemical composition of indium compounds in their toxicity and distribution in the body has not been sufficiently investigated. Therefore, the aim of this study was to examine the effects of particle size and the chemical composition of indium compounds on their toxicity and distribution. Methods: Male Sprague-Dawley rats were exposed to two different-sized indium oxides (average particle sizes under 4,000 nm [IO_4000] and 100 nm [IO_100]) and one nano-sized indium-tin oxide (ITO; average particle size less than 50 nm) by inhalation for 6 hr daily, 5 days per week, for 4 weeks at approximately
of indium by mass concentration. Results: We observed differences in lung weights and histopathological findings, differential cell counts, and cell damage indicators in the bronchoalveolar lavage fluid between the normal control group and IO- or ITO-exposed groups. However, only ITO affected respiratory functions in exposed rats. Overall, the toxicity of ITO was much higher than that of IOs; the toxicity of IO_4000 was higher than that of IO_100. A 4-week recovery period was not sufficient to alleviate the toxic effects of IO and ITO exposure. Inhaled indium was mainly deposited in the lungs. ITO in the lungs was removed more slowly than IOs; IO_4000 was removed faster than IO_100. IOs were not distributed to other organs (i.e., the brain, liver, and spleen), whereas ITO was. Concentrations of indium in the blood and organ tissues were higher at 4 weeks after exposure. Conclusions: The effect of particle size on the toxicity of indium compounds was not clear, whereas chemical composition clearly affected toxicity; ITO showed much higher toxicity than that of IO.