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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 24, Issue 4 - Dec 2008
Volume 24, Issue 3 - Sep 2008
Volume 24, Issue 2 - Jun 2008
Volume 24, Issue 1 - Mar 2008
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Methylated Organic Metabolites of Arsenic and their Cardiovascular Toxicities
Bae, Ok-Nam ; Lim, Kyung-Min ; Noh, Ji-Yoon ; Kim, Keun-Young ; Lim, Eun-Kyung ; Chung, Jin-Ho ;
Toxicological Research, volume 24, issue 3, 2008, Pages 161~167
DOI : 10.5487/TR.2008.24.3.161
Recently, arsenic-toxicity has become the major focus of strenuous assessment and dynamic research from the academy and regulatory agency. To elucidate the cause and the mechanism underlying the serious adverse health effects from chronic ingestion of arsenic-contaminated drinking water, numerous studies have been directed on the investigation of arsenic-toxicity using various in vitro as well as in vivo systems. Neverthless, some questions for arsenic effects remain unexplained, reflecting the contribution of unknown factors to the manifestation of arsenic-toxicity. Interestingly, very recent studies on arsenic metabolites have discovered that trivalent methylated arsenicals show stronger cytotoxic and genotoxic potentials than inorganic arsenic or pentavalent metabolites, arguing that these metabolites could play a key role in arsenic-associated disorders. In this review, recent progress and literatures are summarized on the metabolism of trivalent methylated metabolites and their toxicity on body systems including cardiovascular system in an effort to provide an insight into the future research on arsenic-associated disorders.
Elevation of Nitric Oxide Synthase Activity by Dimethyladenosine from Silkworm Pupae in Aged Rats
Ahn, Mi-Young ; Han, Jea-Woong ; Hong, Yoo-Na ; Hwang, Jae-Sam ;
Toxicological Research, volume 24, issue 3, 2008, Pages 169~174
DOI : 10.5487/TR.2008.24.3.169
This study examined the mechanisms underlying the effects of the vasorelaxation active substance(VAS), dimethyladenosine-5`-L-arabinose, and its partial purification fraction on nitric oxide synthase in improving erectile dysfunction with particular focus on the nitric oxide (NO)-cGMP pathways. Two rat models, 9-month-old SD rats and 11-month-old SD rats, were given VAS(40 mg/kg per day) for 4 days, The aqueous fraction of silworm male pupae extract; semi-purified VAS(100 mg/kg per day) for 10 days, respectively. The NOS activities of the following three enzymes were examined: neuronal NO synthase(nNOS), inducible NOS(iNOS), endothelial NOS(eNOS), vascular endothelial growth factor on endothelial cells(VEGF) and anti-inflammation effect of Tumor necrosis factor-
. The results showed increases in the nitric oxide synthase activities. Western blotting of the tissue homogenate showed an increase in the nNOS level in the brain and tongue, and an increase in the endothelial NO synthase(eNOS) level in penis. However, there was little association with VEGF production in HUVEC endothelial cells and no relationship with TNF-
which showed low levels.
Activation Mechanism of Protein Kinase B by DNA-dependent Protein Kinase Involved in the DNA Repair System
Li, Yuwen ; Piao, Longzhen ; Yang, Keum-Jin ; Shin, Sang-Hee ; Shin, Eul-Soon ; Park, Kyung-Ah ; Byun, Hee-Sun ; Won, Min-Ho ; Choi, Byung-Lyul ; Lee, Hyun-Ji ; Kim, Young-Rae ; Hong, Jang-Hee ; Hur, Gang-Min ; Kim, Jeong-Lan ; Cho, Jae-Youl ; Seok, Jeong-Ho ; Park, Jong-Sun ;
Toxicological Research, volume 24, issue 3, 2008, Pages 175~182
DOI : 10.5487/TR.2008.24.3.175
DNA-dependent protein kinase(DNA-PK) is involved in joining DNA double-strand breaks induced by ionizing radiation or V(D)J recombination and is activated by DNA ends and composed of a DNA binding subunit, Ku, and a catalytic subunit, DNA-PKcs. It has been suggested that DNA-PK might be
upstream kinase for protein kinase B(PKB). In this report, we showed that Ser473 phosphorylation in the hydrophobic-motif of PKB is blocked in DNA-PK knockout mouse embryonic fibroblast cells(MEFs) following insulin stimulation, while there is no effect on Ser473 phosphorylation in DNA-PK wild type MEF cells. The observation is further confirmed in human glioblastoma cells expressing a mutant form of DNA-PK(M059J) and a wild-type of DNA-PK(M059K), indicating that DNA-PK is indeed important for PKB activation. Furthermore, the treatment of cells with doxorubicin, DNA-damage inducing agent, leads to PKB phosphorylation on Ser473 in control MEF cells while there is no response in DNA-PK knockout MEF cells. Together, these results proposed that DNA-PK has a potential role in insulin signaling as well as DNA-repair signaling pathway.
Strain-dependent Differences of Locomotor Activity and Hippocampus-dependent Learning and Memory in Mice
Kim, Joong-Sun ; Yang, Mi-Young ; Son, Yeong-Hoon ; Kim, Sung-Ho ; Kim, Jong-Choon ; Kim, Seung-Joon ; Lee, Yong-Duk ; Shin, Tae-Kyun ; Moon, Chang-Jong ;
Toxicological Research, volume 24, issue 3, 2008, Pages 183~188
DOI : 10.5487/TR.2008.24.3.183
The behavioral phenotypes of out-bred ICR mice were compared with those of in-bred C57BL/6 and BALB/c mice. In particular, this study examined the locomotor activity and two forms of hippocampus-dependent learning paradigms, passive avoidance and object recognition memory. The basal open-field activity of the ICR strain was greater than that of the C57BL/6 and BALB/c strains. In the passive avoidance task, all the mice showed a significant increase in the cross-over latency when tested 24 hours after training. The strength of memory retention in the ICR mice was relatively weak and measurable, as indicated by the shorter cross-over latency than the C57BL/6 and BALB/c mice. In the object recognition memory test, all strains had a significant preference for the novel object during testing. The index for the preference of a novel object was lower for the ICR and BALB/c mice. Nevertheless, the variance and the standard deviation in these strains were comparable. Overall, these results confirm the strain differences on locomotor activity and hippocampus-dependent learning and memory in mice.
Effects of DHU001, a Mixed Herbal Formula on Acute Inflammation in Mice
Back, Young-Doo ; Lee, Hyeung-Sik ; Ku, Sae-Kwang ;
Toxicological Research, volume 24, issue 3, 2008, Pages 189~194
DOI : 10.5487/TR.2008.24.3.189
The effects of DHU001, a mixed herbal formula consisted of 7 types aqueous extracts for treating respiratory disorders were observed on xylene-induced acute inflammation. The xylene was topically applied 60 min after administration of 500, 250 and 125 mg/kg of DHU001, and all animals were sacrificed 2 hrs after xylene application. The changes on ear weights, histolopathological analyses of ear were evaluated and compared to those of indomethacin and dexamethasone(15 mg/kg treated)-Both of drugs are well-known by anti-inflammatory agents. Xylene application resulted in marked increases in induced ear weights as compared with intact control ear. Severe vasodilation, edematous changes of ear skin and increase in the thickness of the ear tissues, neutrophil infiltration as acute inflammation were detected in xylene-treated control ears at histopathological observation. However, these xylene-induced acute inflammatory changes were dose-dependently decreased by oral treatment of DHU001. Therefore, it is concluded that DHU001 has favorable anti-inflammatory effects on xylene-applicated acute ear inflamed mice.
Effects of Oral Rutaecarpine on the Pharmacokinetics of Intravenous Chlorzoxazone in Rats
Bista, Sudeep R. ; Lee, Sang-Kyu ; Thapa, Dinesh ; Kang, Mi-Jeong ; Seo, Young-Min ; Kim, Ju-Hyun ; Kim, Dong-Hyeon ; Jahng, Yurng-Dong ; Kim, Jung-Ae ; Jeong, Tae-Cheon ;
Toxicological Research, volume 24, issue 3, 2008, Pages 195~199
DOI : 10.5487/TR.2008.24.3.195
It has been reported that hepatic microsomal cytochrome P450(CYP) 2E1 is responsible for the metabolism of chlorzoxazone(CZX) to 6-hydroxychlorzoxazone. The present study was undertaken to assess the possible interaction of rutaecarpine, an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa, with CZX. Male Spraque-Dawley rats were administered with 80 mg/kg/day of oral rutaecarpine for three consecutive days. Twenty four hr after the pre-treatment with rutaecarpine, the rats were treated with 20 mg/kg of intravenous CZX. Rat hepatic microsomes isolated from rutaecarpine-treated rats showed greater(50% increase) activity of p-nitrophenol hydroxylase(a marker of CYP2E1) when compared with the control rats. Compared with control rats, the AUC of CZX was significantly smaller(84% decrease) possibly due to significantly faster CL(646% increase) in rats pretreated with rutaecarpine. This could be, at least partially, due to induction of CYP2E1 by rutaecarpine.
Changes in the Expression of Ras-family Genes in Rats Exposed to Formaldehyde by Inhalation
Li, Guang-Yong ; Lee, Hye-Young ; Choi, You-Jin ; Lee, Mi-Ock ; Shin, Ho-Sang ; Kim, Hyeon-Young ; Lee, Sung-Bae ; Lee, Byung-Hoon ;
Toxicological Research, volume 24, issue 3, 2008, Pages 201~206
DOI : 10.5487/TR.2008.24.3.201
Exposure to formaldehyde(FA) is closely associated with adverse health effects such as irritation, inflammation, and squamous cell carcinomas of the nasal cavities. Owing to its rapid metabolism and elimination, exposure to FA does not always result in an increased concentration in blood or urine of animals and humans. Therefore, the development of biomarkers for FA exposure is necessary for risk assessment. In the present study, the effects of FA were investigated on the expression of genes involved in the MAPK pathway in vitro and results confirmed in rats exposed to FA by inhalation. Treatment of Hs 680.Tr human tracheal epithelial cells with FA induced gene expression for PDGFA, TNFSF11, SHC1, and HRAS. HRAS expression was also increased in tracheas of rats exposed to FA. In addition, FA exposure induced the expression of RASSF4, a member of the Rasassociation domain family of Ras effectors, in rat tracheas. In conclusion, data showed FA-inducible expression of genes involved in the MAPK pathway occurred and increased expression of HRAS and RASSF4 was noted in rat tracheas subchronically exposed to FA by inhalation. These genes may serve as molecular targets of FA toxicity facilitating the understanding of the toxic mechanism.
Determination of Methoxyfenozide Residues in Water and Soil by Liquid Chromatography: Evaluation of its Environmental Fate Under Laboratory Conditions
Choi, Jeong-Heui ; Mamun, M.I.R. ; Shin, Eun-Ho ; Kim, Hee-Kwon ; El-Aty, A.M. Abd ; Shim, Jae-Han ;
Toxicological Research, volume 24, issue 3, 2008, Pages 207~212
DOI : 10.5487/TR.2008.24.3.207
Pesticide residues play several key roles as environmental and food pollutants and it is crucial to develop a method for the rapid determination of pesticide residues in environments. In this study, a simple, effective, and sensitive method has been developed for the quantitative analysis of methoxyfenozide in water and soil when kept under laboratory conditions. The content of methoxyfenozide in water and soil was analyzed by first purifying the compound through liquid-liquid extraction and partitioning followed by florisil gel filtration. Upon the completion of the purification step the residual levels were monitored through high performance liquid chromatography(HPLC) using a UV absorbance detector. The average recoveries of methoxyfenozide from three replicates spiked at two different concentrations and were ranged from 83.5% to 110.3% and from 98.1% to 102.8% in water and soil, respectively. The limits of detection(LODs) and limits of quantitation(LOQs) were 0.004 vs. 0.012 ppm and 0.008 vs. 0.024 ppm, respectively. The method was successfully applied to evaluate the behavioral fate of a 21% wettable powder(WP) methoxyfenozide throughout the course of 14 days. A first-order model was found to accurately fit the dissipation of methoxyfenozide in water with and a
value of 3.03 days was calculated from the fit. This result indicates that methoxyfenozide dissipates rapidly and does not accumulate in water.
Micronucleus Test of Kong-Jin-Dan, a Polyherbal Formula, in Bone Marrow Cells of Male ICR Mice
Lee, Sang-Nam ; Park, Ji-Ha ; Ku, Sae-Kwang ;
Toxicological Research, volume 24, issue 3, 2008, Pages 213~218
DOI : 10.5487/TR.2008.24.3.213
In this research, the genotoxic effects of Kong-Jin-Dan(KJD), a polyherbal formula were evaluated using the mouse micronucleus test. KJD was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2000, 1000 and 500 mg/kg. Cyclophosphamide was used as a known genotoxic agent in a positive control. The appearance of a micronucleus is used as an index for genotoxic potential. In addition, the changes on the total white blood cells and differential counts on the lymphocytes, neutrophils, eosinophils, basophils and monocytes in the prepared blood smears were also conducted to observe the possible immunosuppress. The results obtained indicated that KJD shows no genotoxicity effects up to 2000 mg/kg dosing levels, but KJD shows slight increased trends in the blood total leukocyte numbers as pharmacological effects of immune stimulation. In addition, it is also considered that there were no problems from cytotoxicity of KJD tested in this study because the polychromatic erythrocyte ratio was detected as > 0.42 in all tested groups.
Toxicity Screening of Single Dose of Inorganic and Organic Arsenics on Hematological and Serum Biochemical Parameters in Male Cynomolgus Monkeys
Kim, Choong-Yong ; Han, Kang-Hyun ; Heo, Jeong-Doo ; Han, Eui-Sik ; Yum, Young-Na ; Lee, Jin-Young ; Park, Kyung-Su ; Im, Ruth ; Choi, Seong-Jin ; Park, Jung-Duck ;
Toxicological Research, volume 24, issue 3, 2008, Pages 219~225
DOI : 10.5487/TR.2008.24.3.219
A screening study of the acute toxicity of organic arsenics such as arsenobetaine and arsenocholine, a product of arsenic methylation metabolite, and inorganic arsenic was carried out to examine hematological and serum biochemical parameters in cynomolgus monkeys(Macaca fascicularis). We found soft and liquid feces, and vomiting in all treated groups with inorganic and organic arsenics. The monkeys in inorganic arsenic-treated group showed a significant increase in vomiting frequency compared with those in three organic arsenics-treated groups. These results suggest that inorganic arsenic might be more toxic than three other organic arsenics tested. The monkeys in inorganic arsenic-treated group showed a decrease in platelet and an increase in monocyte on day 4 and the monkeys in arsenocholine-treated group showed an increase in reticulocyte percentage on day 8. The monkeys in inorganic-treated group also showed decreases in AST and ALT values and the monkeys in arsenobetaine-treated group showed a decrease in AST value and an increase in T-CHO value. However, these hematological and biochemical changes were within the physiological ranges, showing that the single dose of inorganic and organic arsenics did not affect at least hematological and serum biochemical parameters. The present study of toxicity with single dose of arsenics provides valuable indicators for longer term study of toxicity of repeated doses of arsenics in primates.
Analysis of Lead Ions in a Waste Solution Using Infrared Photo-Diode Electrode
Ly, Suw-Young ; Lee, Hyun-Kuy ; Kwak, Kyu-Ju ; Ko, Jun-Seok ; Lee, Jeong-Jae ; Cho, Jin-Hee ; Kim, Ki-Hong ; Kim, Min-Seok ; Lee, So-Jung ;
Toxicological Research, volume 24, issue 3, 2008, Pages 227~233
DOI : 10.5487/TR.2008.24.3.227
To detect lead ions using electrochemical voltammetric analysis, Infrared Photo-Diode Electrode(IPDE) was applied via cyclic and square wave stripping voltammetry. Lead ions were deposited at 0.5 V(versus Ag/AgCl) accumulation potential. Instrumental measurements systems were made based on a simple and compact detection system. The stripping voltammetric and cyclic voltammetric optimal parameters were searched. The results yielded a cyclic range of
Pb(II) and a square wave stripping working range of
Pb(II). The relative standard deviation at 2 and 4
Pb(II) was 0.04% and 0.02%(n