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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 29, Issue 4 - Dec 2013
Volume 29, Issue 3 - Sep 2013
Volume 29, Issue 2 - Jun 2013
Volume 29, Issue 1 - Mar 2013
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Post-Translational Modification of Proteins in Toxicological Research: Focus on Lysine Acylation
Lee, Sangkyu ;
Toxicological Research, volume 29, issue 2, 2013, Pages 81~86
DOI : 10.5487/TR.2013.29.2.081
Toxicoproteomics integrates the proteomic knowledge into toxicology by enabling protein quantification in biofluids and tissues, thus taking toxicological research to the next level. Post-translational modification (PTM) alters the three-dimensional (3D) structure of proteins by covalently binding small molecules to them and therefore represents a major protein function diversification mechanism. Because of the crucial roles PTM plays in biological systems, the identification of novel PTMs and study of the role of PTMs are gaining much attention in proteomics research. Of the 300 known PTMs, protein acylation, including lysine formylation, acetylation, propionylation, butyrylation, malonylation, succinylation, and crotonylation, regulates the crucial functions of many eukaryotic proteins involved in cellular metabolism, cell cycle, aging, growth, angiogenesis, and cancer. Here, I reviewed recent studies regarding novel types of lysine acylation, their biological functions, and their applicationsin toxicoproteomics research.
Safety Evaluation of Topical Valproate Application
Choi, Sun Young ; Seop, Song Yi ; Hyun, Moo Yeol ; Yoo, Kwang Ho ; Kim, Beom Joon ; Kim, Myeung Nam ; Cho, Jae-We ;
Toxicological Research, volume 29, issue 2, 2013, Pages 87~90
DOI : 10.5487/TR.2013.29.2.087
The potential role of topical valproate (VPA) in hair regrowth has been recently suggested. However, safety reports of VPA as a topical formulation are lacking. Therefore, in the present study, we investigated whether VPA causes skin irritation in humans. We first performed a cell viability test and showed that VPA did not exhibit toxicity toward HaCaT keratinocytes, fibroblasts, and RBL-3H mast cells. We then performed clinical patch test and skin irritation test through transdermal drug delivery with the help of microneedle rollers. No significant findings were obtained in the clinical patch test. In the skin irritation test, only 1 patient showed erythema at 1 hr, but the irritation reaction faded away within a few hours. Erythema and edema were not observed at 24 hr. We concluded that VPA has minimal potential to elicit skin irritation. Therefore, we consider that VPA can safely be applied to human skin.
Single Oral Dose Toxicity Study of Prebrewed Armeniacae Semen in Rats
Park, Ji-Ha ; Seo, Bu-Il ; Cho, Su-Yeon ; Park, Kyu-Ryul ; Choi, Seung-Hoon ; Han, Chang-Kyun ; Song, Chang-Hyun ; Park, Soo-Jin ; Ku, Sae-Kwang ;
Toxicological Research, volume 29, issue 2, 2013, Pages 91~98
DOI : 10.5487/TR.2013.29.2.091
Armeniacae semen (AS) has been considered a toxic herb in the Korean medicine as it contains hydrogen cyanide and amygdalin, especially in its endocarp. Therefore, prebrewed AS that is devoid of endocarp has been traditionally used. In the present study, amygdalin content of the prebrewed AS was significantly lower (
; p<0.01) than the content in the extract that contained the endocarps (
); amygdalin content corresponded to 10% of the extract in the present study. Because of single oral dose toxicity of prebrewed AS according to the recommendation of Korea Food and Drug Administration Guidelines (2009-116, 2009), which was based on single oral dose toxicity study of prebrewed AS, mortality due to toxic principles was significantly reduced. In this study, 2,000 mg/kg of prebrewed AS led to death of 1 female rat and 1 male rat at the end of 2 hr of administration. Based on these results, the 50% lethal dose in both male and female rats was determined to be 9279.5 mg/kg. Seizure, loss of locomotion, and increases in respiration and heart rate were observed as prebrewed AS treatment-related toxicological signs; these signs were restrictedly manifested in the prebrewed AS (2,000 mg/kg)-treated rats. In addition, no changes were observed in body weight, organ weight, gross features, and histopathological parameters with 2,000 mg/kg of AS in both male and female rats. These findings serve as direct evidence that amygdalin in AS is the toxic principle, which can be reduced by the traditional prebrewing method involving the exclusion of endocarp.
In Vitro Evaluation of Antimicrobial Activity of Lactic Acid Bacteria against Clostridium difficile
Lee, Joong-Su ; Chung, Myung-Jun ; Seo, Jae-Gu ;
Toxicological Research, volume 29, issue 2, 2013, Pages 99~106
DOI : 10.5487/TR.2013.29.2.099
Clostridium difficile infection (CDI) has become a significant threat to public health. Although broad-spectrum antibiotic therapy is the primary treatment option for CDI, its use has evident limitations. Probiotics have been proved to be effective in the treatment of CDI and are a promising therapeutic option for CDI. In this study, 4 strains of lactic acid bacteria (LAB), namely, Lactobacillus rhamnosus (LR5), Lactococcuslactis (SL3), Bifidobacterium breve (BR3), and Bifidobacterium lactis (BL3) were evaluated for their anti-C. difficile activity. Co-culture incubation of C. difficile (
CFU/ml) with each strain of LAB indicated that SL3 possessed the highest antimicrobial activity over a 24-hr period. The cell-free supernatants of the 4 LAB strains exhibited
values between 0.424 mg/ml (SL3) and 1.318 (BR3) mg/ml. These results may provide a basis for alternative therapies for the treatment of C. difficile-associated gut disorders.
Comparison between Source-induced Dissociation and Collision-induced Dissociation of Ampicillin, Chloramphenicol, Ciprofloxacin, and Oxytetracycline via Mass Spectrometry
Lee, Seung Ha ; Choi, Dal Woong ;
Toxicological Research, volume 29, issue 2, 2013, Pages 107~114
DOI : 10.5487/TR.2013.29.2.107
Mass spectrometry (MS) is a very powerful instrument that can be used to analyze a wide range of materials such as proteins, peptides, DNA, drugs, and polymers. The process typically involves either chemical or electron (impact) ionization of the analyte. The resulting charged species or fragment is subsequently identified by the detector. Usually, single mass uses source-induced dissociation (SID), whereas mass/mass uses collision-induced dissociation (CID) to analyze the chemical fragmentations Each technique has its own advantages and disadvantages. While CID is most effective for the analysis of pure substances, multiple-step MS is a powerful technique to get structural data. Analysis of veterinary drugs ampicillin, chloramphenicol, ciprofloxacin, and oxytetracycline serves to highlight the slight differences between SID and CID. For example, minor differences were observed between ciprofloxacin and oxytetracycline via SID or CID. However, distinct fragmentation patterns were observed for ampicllin depending on the analysis method. Both SID and CID showed similar fragmentation spectra but different signal intensities for chloramphenicol. There are several factors that can influence the fragmentation spectra, such as the collision energy, major precursor ion, electrospray mode (positive or negative), and sample homogeneity. Therefore, one must select a fragmentation method on an empirical and case-by-case basis.
Effects of Beryllium on Human Serum Immunoglobulin and Lymphocyte Subpopulation
Kim, Ki-Woong ; Kim, DaeSeong ; Won, Yong Lim ; Kang, Seong-Kyu ;
Toxicological Research, volume 29, issue 2, 2013, Pages 115~120
DOI : 10.5487/TR.2013.29.2.115
To investigate the effects of short-term exposure of beryllium on the human immune system, the proportion of T-lymphocytes such as CD3+, CD4+, CD8+, CD95, and NK cells, and the proportion of B cells and
level in peripheral blood and immunoglobulins in the serum of 43 exposed workers and 34 healthy control subjects were studied. External exposure to beryllium was measured by atomic absorption spectrometer as recommended by the NIOSH analytical method 7300. T lymphocyte subpopulation analysis was carried out with flow cytometer. The working duration of exposed workers was less than 3 months and the mean ambient beryllium level was
in molding (furnace), deforming (grinding), and sorting processes, respectively (cited from Kim et al., 2008). However, ambient beryllium level after process change was non-detectable (<
). The number of T lymphocytes and the amount of immunoglobulins in the beryllium-exposed workers and control subjects were not significantly different, except for the total number of lymphocytes and CD95 (APO1/FAS). The total number of lymphocytes was higher in the beryllium-exposed individuals than in the healthy control subjects. Multiple logistic regression analysis showed lymphocytes to be affected by beryllium exposure (odd ratio = 7.293; p<0.001). These results show that short-term exposure to beryllium does not induce immune dysfunction but is probably associated with lymphocytes proliferation.
Comparison of Toxicity and Deposition of Nano-Sized Carbon Black Aerosol Prepared With or Without Dispersing Sonication
Kang, Mingu ; Lim, Cheol-Hong ; Han, Jeong-Hee ;
Toxicological Research, volume 29, issue 2, 2013, Pages 121~127
DOI : 10.5487/TR.2013.29.2.121
Nanotoxicological research has shown toxicity of nanomaterials to be inversely related to particle size. However, the contribution of agglomeration to the toxicity of nanomaterials has not been sufficiently studied, although it is known that agglomeration is associated with increased nanomaterial size. In this study, we prepared aerosols of nano-sized carbon black by 2 different ways to verify the effects of agglomeration on the toxicity and deposition of nano-sized carbon black. The 2 methods of preparation included the carbon black dispersion method that facilitated clustering without sonication and the carbon black dispersion method involving sonication to achieve scattering and deagglomeration. Male Sprague-Dawley rats were exposed to carbon black aerosols 6 hr a day for 3 days or for 2 weeks. The median mass aerodynamic diameter of carbon black aerosols averaged
(for aerosol prepared without sonication; group N) and
(for aerosol prepared without sonication; group S). The average concentration of carbon black during the exposure period for group N and group S was
, respectively, in the 3-day experiment. The average concentration during the 2-week experiment was
for group N and group S, respectively. The amount of carbon black deposition in the lungs was significantly higher in group S than in group N in both 3-day and 2-week experiments. The number of total cells, macrophages and polymorphonuclear leukocytes in the bronchoalveolar lavage (BAL) fluid, and the number of total white blood cells and neutrophils in the blood in the 2-week experiment were significantly higher in group S than in normal control. However, differences were not found in the inflammatory cytokine levels (IL-
, IL-6, etc.) and protein indicators of cell damage (albumin and lactate dehydrogenase) in the BAL fluid of both group N and group S as compared to the normal control. In conclusion, carbon black aerosol generated by sonication possesses smaller nanoparticles that are deposited to a greater extent in the lungs than is aerosol formulated without sonication. Additionally, rats were narrowly more affected when exposed to carbon black aerosol generated by sonication as compared to that produced without sonication.
A Study on the Prevention of Salmonella Infection by Using the Aggregation Characteristics of Lactic Acid Bacteria
Kim, Min-Soo ; Yoon, Yeo-Sang ; Seo, Jae-Gu ; Lee, Hyun-Gi ; Chung, Myung-Jun ; Yum, Do-Young ;
Toxicological Research, volume 29, issue 2, 2013, Pages 129~135
DOI : 10.5487/TR.2013.29.2.129
Salmonella is one of the major pathogenic bacteria that cause food poisoning. This study investigated whether heat-killed as well as live Lactobacillus protects host animal against Salmonella infection. Live and heat-killed Lactobacillusacidophilus was administered orally to Sprague-Dawley rats for 2 weeks before the rats were inoculated with Salmonella. Rise in body temperature was moderate in the group that was treated with heat-killed bacteria as compared to the Salmonella control group. The mean amount of feed intake and water consumption of each rat in the heat-killed bacteria group were nearly normal. The number of fecal Salmonellae was comparable between the live and the heat-killed L. acidophilus groups. This finding shows that L. acidophilus facilitates the excretion of Salmonella. Moreover, the levels of pro inflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta, in the heat-killed L. acidophilus group were significantly lower when compared to the levels in the Salmonella control group. These results indicate that nonviable lactic acid bacteria also could play an important role in preventing infections by enteric pathogens such as Salmonella.
Urinary Arsenic Concentrations and their Associated Factors in Korean Adults
Bae, Hye-Sun ; Ryu, Doug-Young ; Choi, Byung-Sun ; Park, Jung-Duck ;
Toxicological Research, volume 29, issue 2, 2013, Pages 137~142
DOI : 10.5487/TR.2013.29.2.137
Arsenic (As) is a well-known human carcinogen and its dietary exposure has been found to be the major route of entry into general population. This study was performed to assess the body levels of As and their associated factors in Korean adults by analyzing total As in urine. Urine and blood samples were collected from 580 adults aged 20 years and older, who had not been exposed to As occupationally. Demographic information was collected with the help of a standard questionnaire, including age, smoking, alcohol intake, job profiles, and diet consumed in the last 24 hrs of the study. Total As, sum of As(III), As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), in urine was determined using atomic absorption spectrometer involving hydride generation method. The geometric mean concentration of total As in urine was
. Urine As was significantly higher in men (
) than in women (
). Age, smoking, alcohol consumption, and job profiles of study subjects did not significantly affect the concentration of As in urine. No significant relationship was observed between body mass index (BMI), Fe, and total cholesterol in serum and urinary As. Urine As level was positively correlated with seaweeds, fishes & shellfishes, and grain intake. A negative correlation between urinary As level and HDL-cholesterol in serum and meat intake was observed. Overall, these results suggest that urinary As concentration could be affected by seafood consumption. Therefore, people who frequently consume seafood and grain need to be monitored for chronic dietary As exposure.
Determination of Cyanogenic Compounds in Edible Plants by Ion Chromatography
Cho, Hye-Jeon ; Do, Byung-Kyung ; Shim, Soon-Mi ; Kwon, Hoonjeong ; Lee, Dong-Ha ; Nah, Ahn-Hee ; Choi, Youn-Ju ; Lee, Sook-Yeon ;
Toxicological Research, volume 29, issue 2, 2013, Pages 143~147
DOI : 10.5487/TR.2013.29.2.143
Cyanogenic glycosides are HCN-producing phytotoxins; HCN is a powerful and a rapidly acting poison. It is not difficult to find plants containing these compounds in the food supply and/or in medicinal herb collections. The objective of this study was to investigate the distribution of total cyanide in nine genera (Dolichos, Ginkgo, Hordeum, Linum, Phaseolus, Prunus, Phyllostachys, Phytolacca, and Portulaca) of edible plants and the effect of the processing on cyanide concentration. Total cyanide content was measured by ion chromatography following acid hydrolysis and distillation. Kernels of Prunus genus are used medicinally, but they possess the highest level of total cyanide of up to 2259.81
/g dry weight. Trace amounts of cyanogenic compounds were detected in foodstuffs such as mungbeans and bamboo shoots. Currently, except for the WHO guideline for cassava, there is no global standard for the allowed amount of cyanogenic compounds in foodstuffs. However, our data emphasize the need for the guidelines if plants containing cyanogenic glycosidesare to be developed as dietary supplements.