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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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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
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Endothelium-derived Relaxing Factors of Small Resistance Arteries in Hypertension
Kang, Kyu-Tae ;
Toxicological Research, volume 30, issue 3, 2014, Pages 141~148
DOI : 10.5487/TR.2014.30.3.141
Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin (
), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions.
NADPH Oxidase and the Cardiovascular Toxicity Associated with Smoking
Kim, Mikyung ; Han, Chang-Ho ; Lee, Moo-Yeol ;
Toxicological Research, volume 30, issue 3, 2014, Pages 149~157
DOI : 10.5487/TR.2014.30.3.149
Smoking is one of the most serious but preventable causes of cardiovascular disease (CVD). Key aspects of pathological process associated with smoking include endothelial dysfunction, a prothrombotic state, inflammation, altered lipid metabolism, and hypoxia. Multiple molecular events are involved in smoking-induced CVD. However, the dysregulations of reactive oxygen species (ROS) generation and metabolism mainly contribute to the development of diverse CVDs, and NADPH oxidase (NOX) has been established as a source of ROS responsible for the pathogenesis of CVD. NOX activation and resultant ROS production by cigarette smoke (CS) treatment have been widely observed in isolated blood vessels and cultured vascular cells, including endothelial and smooth muscle cells. NOX-mediated oxidative stress has also been demonstrated in animal studies. Of the various NOX isoforms, NOX2 has been reported to mediate ROS generation by CS, but other isoforms were not tested thoroughly. Of the many CS constituents, nicotine, methyl vinyl ketone, and
-unsaturated aldehydes, such as, acrolein and crotonaldehyde, appear to be primarily responsible for NOX-mediated cytotoxicity, but additional validation will be needed. Human epidemiological studies have reported relationships between polymorphisms in the CYBA gene encoding p22phox, a catalytic subunit of NOX and susceptibility to smoking-related CVDs. In particular, G allele carriers of A640G and
polymorphisms were found to be vulnerable to smoking-induced cardiovascular toxicity, but results for C242T studies are conflicting. On the whole, evidence implicates the etiological role of NOX in smoking-induced CVD, but the clinical relevance of NOX activation by smoking and its contribution to CVD require further validation in human studies. A detailed understanding of the role of NOX would be helpful to assess the risk of smoking to human health, to define high-risk subgroups, and to develop strategies to prevent or treat smoking-induced CVD.
Towards a Strategic Approaches in Alternative Tests for Pesticide Safety
Jang, Yoonjeong ; Kim, Ji-Eun ; Jeong, Sang-Hee ; Cho, Myung-Haing ;
Toxicological Research, volume 30, issue 3, 2014, Pages 159~168
DOI : 10.5487/TR.2014.30.3.159
Pesticides have provided significant benefits including plant disease control and increased crop yields since people developed and utilized them. However, pesticide use is associated with many adverse effects, which necessitate precise toxicological tests and risk assessment. Most of these methods are based on animal studies, but considerations of animal welfare and ethics require the development of alternative methods for the evaluation of pesticide toxicity. Although the usage of laboratory animals is inevitable in scientific evaluation and alternative approaches have limitations in the whole coverage, continuous effort is necessary to minimize animal use and to develop reliable alternative tests for pesticide evaluation. This review discusses alternative approaches for pesticide toxicity tests and hazard evaluation that have been used in peer-reviewed reports and could be applied in future studies based on the critical animal research principles of reduction, replacement, and refinement.
A New Paradigm Shift for the Green Synthesis of Antibacterial Silver Nanoparticles Utilizing Plant Extracts
Park, Youmie ;
Toxicological Research, volume 30, issue 3, 2014, Pages 169~178
DOI : 10.5487/TR.2014.30.3.169
This review covers general information regarding the green synthesis of antibacterial silver nanoparticles. Owing to their antibacterial properties, silver nanoparticles are widely used in many areas, especially biomedical applications. In green synthesis practices, the chemical reducing agents are eliminated, and biological entities are utilized to convert silver ions to silver nanoparticles. Among the various biological entities, natural plant extracts have emerged as green reducing agents, providing eco-friendly routes for the preparation of silver nanomaterials. The most obvious merits of green synthesis are the increased biocompatibility of the resulting silver nanoparticles and the ease with which the reaction can be carried out. This review summarizes some of the plant extracts that are used to produce antibacterial silver nanoparticles. Additionally, background information regarding the green synthesis and antibacterial activity of silver nanoparticles is provided. Finally, the toxicological aspects of silver nanoparticles are briefly mentioned.
The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a "Central Dogma" for Toxic Mechanisms?
Park, Yeong-Chul ; Lee, Sundong ; Cho, Myung-Haing ;
Toxicological Research, volume 30, issue 3, 2014, Pages 179~184
DOI : 10.5487/TR.2014.30.3.179
Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems.
Analysis of Statistical Methods Currently used in Toxicology Journals
Na, Jihye ; Yang, Hyeri ; Bae, SeungJin ; Lim, Kyung-Min ;
Toxicological Research, volume 30, issue 3, 2014, Pages 185~191
DOI : 10.5487/TR.2014.30.3.185
Statistical methods are frequently used in toxicology, yet it is not clear whether the methods employed by the studies are used consistently and conducted based on sound statistical grounds. The purpose of this paper is to describe statistical methods used in top toxicology journals. More specifically, we sampled 30 papers published in 2014 from Toxicology and Applied Pharmacology, Archives of Toxicology, and Toxicological Science and described methodologies used to provide descriptive and inferential statistics. One hundred thirteen endpoints were observed in those 30 papers, and most studies had sample size less than 10, with the median and the mode being 6 and 3 & 6, respectively. Mean (105/113, 93%) was dominantly used to measure central tendency, and standard error of the mean (64/113, 57%) and standard deviation (39/113, 34%) were used to measure dispersion, while few studies provide justifications regarding why the methods being selected. Inferential statistics were frequently conducted (93/113, 82%), with one-way ANOVA being most popular (52/93, 56%), yet few studies conducted either normality or equal variance test. These results suggest that more consistent and appropriate use of statistical method is necessary which may enhance the role of toxicology in public health.
Methylglyoxal Induces Mitochondrial Dysfunction and Cell Death in Liver
Seo, Kyuhwa ; Ki, Sung Hwan ; Shin, Sang Mi ;
Toxicological Research, volume 30, issue 3, 2014, Pages 193~198
DOI : 10.5487/TR.2014.30.3.193
Degradation of glucose is aberrantly increased in hyperglycemia, which causes various harmful effects on the liver. Methylglyoxal is produced during glucose degradation and the levels of methylglyoxal are increased in diabetes patients. In this study we investigated whether methylglyoxal induces mitochondrial impairment and apoptosis in HepG2 cells and induces liver toxicity in vivo. Methylglyoxal caused apoptotic cell death in HepG2 cells. Moreover, methylglyoxal significantly promoted the production of reactive oxygen species (ROS) and depleted glutathione (GSH) content. Pretreatment with antioxidants caused a marked decrease in methylglyoxal-induced apoptosis, indicating that oxidant species are involved in the apoptotic process. Methylglyoxal treatment induced mitochondrial permeability transition, which represents mitochondrial impairment. However, pretreatment with cyclosporin A, an inhibitor of the formation of the permeability transition pore, partially inhibited methylglyoxal-induced cell death. Furthermore, acute treatment of mice with methylglyoxal increased the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indicating liver toxicity. Collectively, our results showed that methylglyoxal increases cell death and induces liver toxicity, which results from ROS-mediated mitochondrial dysfunction and oxidative stress.
Comparative Study on the EC
Value in Single and Mixtures of Dimethylformamide, Methyl Ethyl Ketone, and Toluene
Kim, Ki-Woong ; Won, Yong Lim ; Park, Dong Jin ; Kim, Doh-Hee ; Song, Kwan Young ;
Toxicological Research, volume 30, issue 3, 2014, Pages 199~204
DOI : 10.5487/TR.2014.30.3.199
The aim of this research was to improve our understanding of human toxicity due to exposure to DMF, MEK, or TOL individually as compared to exposure to DMF-MEK or DMF-TOL mixtures, by comparing
values as well as the morphological changes in HepG2 cells treated with these substances. We found that there was marked cell necrosis in the groups treated with mixtures than in those treated with the compounds alone, and that the amount of cell death and the
value were more dependent on MEK and TOL than on DMF. Moreover, analysis of the changes in effective concentration curves revealed that MEK had an antagonistic effect on the human toxicity of DMF, whereas TOL had a synergistic effect. Accordingly, these results suggest that in workplaces involved in the manufacture of synthetic leather, mixtures of DMF and TOL should be avoided as much as possible in order to minimize environmental toxicity and protect the health of the workers.
Effects of Didecyldimethylammonium Chloride on Sprague-Dawley Rats after Two Weeks of Inhalation Exposure
Lim, Cheol-Hong ; Chung, Yong-Hyun ;
Toxicological Research, volume 30, issue 3, 2014, Pages 205~210
DOI : 10.5487/TR.2014.30.3.205
Didecyldimethylammonium chloride (DDAC) is used for various purposes, such as a fungicide for coolants, an antiseptic for wood, and disinfectant for cleaning. Despite the increasing likelihood of DDAC inhalation, available data on its toxicity from inhalation are scarce. Therefore, this study was aimed at confirming the toxicity of DDAC after inhalation exposure for 2 wk. Male Sprague-Dawley rats were exposed to approximately
DDAC aerosols in whole-body exposure chambers. After DDAC exposure for 2 wk, effects of DDAC on body weight, blood, bronchoalveolar lavage (BAL), and the lungs were verified. The mass median aerodynamic diameter of DDAC aerosols was
and the geometric standard deviation was 2.75. The concentrations of DDAC aerosols for the low, medium, and high groups were
, respectively. Body weight gain was significantly influenced by DDAC exposure. In the high group, a body weight decrease of 2.6 g was observed, whereas a 25.8 g increase was observed in the normal control group after the first 3 days. The low and medium groups showed 23.3 g and 20.4 g increases, respectively, after the first 3 days. Decreases in body weight were recovered during the next 4 days. In contrast, no changes were noted in hematological and blood biochemistry parameters after DDAC exposure. Furthermore, only mild effects were observed on bronchoalveolar cell differentiation counts and cell damage parameters in the BAL fluids of the medium and high groups. Although inflammatory cell infiltration and interstitial pneumonia were partially observed, fibrosis was not found in the lungs of the medium and high groups. In conclusion, body weight gain and the lungs were mainly affected by DDAC exposure. The no-observed-adverse-effect level (NOAEL) for DDAC was determined as
In Vitro Genotoxicity Assessment of a Novel Resveratrol Analogue, HS-1793
Jeong, Min Ho ; Yang, Kwangmo ; Lee, Chang Geun ; Jeong, Dong Hyeok ; Park, You Soo ; Choi, Yoo Jin ; Kim, Joong Sun ; Oh, Su Jung ; Jeong, Soo Kyung ; Jo, Wol Soon ;
Toxicological Research, volume 30, issue 3, 2014, Pages 211~220
DOI : 10.5487/TR.2014.30.3.211
Resveratrol has received considerable attention as a polyphenol with various biological effects such as anti-inflammatory, anti-oxidant, anti-mutagenic, anti-carcinogenic, and cardioprotective properties. As part of the overall safety assessment of HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, we assessed genotoxicity in three in vitro assays: a bacterial mutation assay, a comet assay, and a chromosomal aberration assay. In the bacterial reverse mutation assay, HS-1793 did not increase revertant colony numbers in S. typhimurium strains (TA98, TA100, TA1535 and TA1537) or an E. coli strain (WP2 uvrA) regardless of metabolic activation. HS-1793 showed no evidence of genotoxic activity such as DNA damage on L5178Y
mouse lymphoma cells with or without the S9 mix in the in vitro comet assay. No statistically significant differences in the incidence of chromosomal aberrations following HS-1793 treatment was observed on Chinese hamster lung cells exposed with or without the S9 mix. These results provide additional evidence that HS-1793 is non-genotoxic at the dose tested in three standard tests and further supports the generally recognized as safe determination of HS-1793 during early drug development.