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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 26, Issue 4 - Dec 2010
Volume 26, Issue 3 - Sep 2010
Volume 26, Issue 2 - Jun 2010
Volume 26, Issue 1 - Mar 2010
Selecting the target year
Use of Antioxidants to Prevent Cyclosporine A Toxicity
Lee, Jin-Hwa ;
Toxicological Research, volume 26, issue 3, 2010, Pages 163~170
DOI : 10.5487/TR.2010.26.3.163
Cyclosporine A (CsA) is a potent immunosuppressor that is widely used in transplant surgery and the treatment of several autoimmune diseases. However, major side effects of CsA such as nephrotoxicity, hepatotoxicity, neurotoxicity and cardiovascular diseases have substantially limited its usage. Although molecular mechanisms underlying these adverse effects are not clearly understood, there is some evidence that suggests involvement of reactive oxygen species (ROS). In parallel, protective effects of various antioxidants have been demonstrated by many research groups. Extensive studies of CsA-induced nephrotoxcity have confirmed that the antioxidants can restore the damaged function and structure of kidney. Subsequently, there have appeared numerous reports to demonstrate the positive antioxidant effects on liver and other organ damages by CsA. It may be timely to review the ideas to envisage the relationship between ROS and the CsA-induced toxicity. This review is comprised of a brief description of the immunosuppressive action and the secondary effects of CsA, and a synopsis of reports regarding the antioxidant treatments against the ROS-linked CsA toxicity. A plethora of recent reports suggest that antioxidants can help reduce many CsA`s adverse effects and therefore might help develop more effective CsA treatment regimens.
Bioactivation of Aromatic Amines by Human CYP2W1, An Orphan Cytochrome P450 Enzyme
Eun, Chang-Yong ; Han, Song-Hee ; Lim, Young-Ran ; Park, Hyoung-Goo ; Han, Jung-Soo ; Cho, Kyoung-Sang ; Chun, Young-Jin ; Kim, Dong-Hak ;
Toxicological Research, volume 26, issue 3, 2010, Pages 171~175
DOI : 10.5487/TR.2010.26.3.171
The human genome contains approximately 13 orphan cytochrome P450 (P450, CYP) genes, of which the apparent function or substrate has not been identified. However, they seem to possess their own biological relevance in some tissues or developmental stages. Here, we characterized the heterologously expressed CYP2W1, an orphan P450 enzyme. The recombinant CYP2W1 protein containing a
(His)-tag at Nterminus has been expressed in Escherichia coli and purified. Expression level of CYP2W1 holoenzyme was around 500 nmol P450 holoenzyme per liter culture medium. The reduced CO difference spectrum of CYP2W1 showed a maximum absorption at 449 nm. CYP2W1 indicated the significant induction to bioactivate Trp-P-1, MeIQ, and IQ in E. coli DJ701 tester strain. However, the bioactivation of B[
]P, and NNK by CYP2W1 was relatively low. The model structure of CYP2W1 suggested the characteristic P450 folds with the lengths and orientations of the individual secondary elements. The F-G loop is situated on the distal side of heme to accommodate the flexibility of active site of CYP2W1. These studies can provide useful information for the finding of its biological roles and structure-function relationships of an orphan CYP2W1 enzyme.
Promotion of cAMP Responsive Element-Binding Protein Activity Ameliorates Radiation-Induced Suppression of Hippocampal Neurogenesis in Adult Mice
Kim, Joong-Sun ; Yang, Mi-Young ; Cho, Jae-Ho ; Kim, Sung-Ho ; Kim, Jong-Choon ; Shin, Tae-Kyun ; Moon, Chang-Jong ;
Toxicological Research, volume 26, issue 3, 2010, Pages 177~183
DOI : 10.5487/TR.2010.26.3.177
This study was performed to examine whether elevated activity of cAMP responsive element-binding protein (CREB) attenuates the detrimental effects of acute gamma (
)-irradiation on hippocampal neurogenesis and related functions. C57BL/6 male mice were treated with rolipram (1.25 mg/kg, i.p., twice a day for 5 consecutive days) to activate the cAMP/CREB pathway against cranial irradiation (2 Gy), and were euthanized at 24 h post-irradiation. Exposure to
-rays decreased both CREB phosphorylation and immunohistochemical markers for neurogenesis, including Ki-67 and doublecortin (DCX), in the hippocampal dentate gyrus (DG). However, the rolipram treatment protected from
-irradiation-induced decreases of CREB phosphorylation, and Ki-67 and DCX immunoreactivity in the hippocampal DG. In an object recognition memory test, mice trained 24 h after acute
-irradiation (2 Gy) showed significant memory impairment, which was attenuated by rolipram treatment. The results suggest that activation of CREB signaling ameliorates the detrimental effects of acute
-irradiation on hippocampal neurogenesis and related functions in adult mice.
Fatty Acid Composition of Adipose Tissues in Obese Mice and SD Rats Fed with Isaria sinclairii Powder
Ahn, Mi-Young ; Seo, Yun-Jung ; Ji, Sang-Deok ; Han, Jea-Woong ; Hwang, Jae-Sam ; Yun, Eun-Young ;
Toxicological Research, volume 26, issue 3, 2010, Pages 185~192
DOI : 10.5487/TR.2010.26.3.185
Isaria sinclairii (Cicada Dongchunghacho) was studied as a potential crude natural food in powdered form. The role of tissue fatty acids in relation to the anti-obesity effects of I. sinclairii (IS) was examined by feeding the powder to SD rats ad libitum at 0, 1.25, 2.5, 5 and 10% (calculated about 8 g/kg) of the feed for a period of 3 months and 6 months. The fatty acid composition profile as indicated GC-MS, showed significantly slight dose-dependent increases in the levels of unsaturated fatty acids, particularly, arachidonic acid (C20: 4n6), oleic acid, linoleic acid, eicosadienoic acid, eicosapentaenoic acid (EPA) (C20: 5) concentration in the the ad libitum IS-fed groups compared to the control group in SD abdominal fat over 6 month period. Over viewing of the SD and Ob mice treated Isaria sinclairii powder; there were increases in the single (mono) unsaturated fatty acids ratio but decreases in polyunsaturated fatty acid. In IS-fed groups in proportion to the treatment period, this Dongchunghacho also induced an increase in the level of same result of unsaturated fatty acid in C57BL/6 obese (ob/ob) mice over a 6-month period treatment compared to those given 10% dry mulberry leaf powder (ML) or silkworm powder mixed with the standard diet.
Inhibitory Effect of 1-O-Hexyl-2,3,5-Trimethylhydroquinone on Dimethylnitrosamine-induced Liver Fibrosis in Male SD Rats
Jung, Yu-Ri ; Lee, Young-Jung ; Lee, Nam-Jin ; Lin, Chun-Mai ; Moon, Jun-Hawn ; Chai, Hee-Yul ; Kang, Jong-Koo ;
Toxicological Research, volume 26, issue 3, 2010, Pages 193~201
DOI : 10.5487/TR.2010.26.3.193
Hepatic fibrosis represents the main complication of most chronic liver disorders and, regardless of its etiology, is characterized by excessive deposition of extracellular matrix components. In this study, we examined that 1-O-Hexyl-2,3,5-Trimethylhydroquinone (HTHQ), a potent anti-oxidative agent, could prevent experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in male SD rats. Except for vehicle control group, other groups were induced hepatic fibrosis by intraperitoneal injection with DMN (10 mg/ml/kg) on 3 consecutive days weekly for 4 weeks. During the same 4 weeks, control and DMN groups were given vehicle and HTHQ 50, 100 and 200 groups were orally administered HTHQ (50, 100, 200 mg/kg respectively). In HTHQ 100 and 200 groups, relative liver weight and serum chemistry level improved significantly. HTHQ reduced hydroxyproline (p < 0.05) and malondialdehyde (p < 0.05) level in the liver. Histopathological examination of H&E, Masson`s trichrome stain showed the reduced fibrotic septa in HTHQ 100 and 200 groups. HTHQ administration showed reduced mRNA level of PDGF (Platelet-derived growth factor),
-smooth muscle actin) and TGF-
(transforming growth factor-
) than DMN-induced hepetic fibrosis animals in the liver tissue. In this study, we showed that HTHQ improves against DMN-induced liver fibrosis in male SD rats.
Standardization of Bronchoalveolar Lavage Method Based on Suction Frequency Number and Lavage Fraction Number Using Rats
Song, Jeong-Ah ; Yang, Hyo-Seon ; Lee, Jin-Soo ; Kwon, Soon-Jin ; Jung, Kyung-Jin ; Heo, Jeong-Doo ; Cho, Kyu-Hyuk ; Song, Chang-Woo ; Lee, Kyu-Hong ;
Toxicological Research, volume 26, issue 3, 2010, Pages 203~208
DOI : 10.5487/TR.2010.26.3.203
Bronchoalveolar lavage (BAL) is a useful tool in researches and in clinical medicine of lung diseases because the BAL fluid contains biochemical and cytological indicators of the cellular response to infection, drugs, or toxicants. However, the variability among laboratories regarding the technique and the processing of the BAL material limits clinical research. The aim of this study was to determine the suction frequency and lavage fraction number necessary to reduce the variability in lavage using male Sprague-Dawley rats. We compared the total cell number and protein level of each lavage fraction and concluded that more cells and protein can be obtained by repetitive lavage with a suction frequency of 2 or 3 than by lavage with a single suction. On the basis of total cell recovery, approximately 70% of cells were obtained from fractions 1~3. The first lavage fraction should be used for evaluation of protein concentration because fractions 2~5 of lavage fluid were diluted in manifolds. These observations were confirmed in bleomycin-induced inflamed lungs of rats. We further compared the BAL data from the whole lobes with data from the right lobes and concluded that BAL data of the right lobes represented data of the whole lobes. However, this conclusion can only be applied to general lung diseases. At the end, this study provides an insight into the technical or analytical problems of lavage study in vivo.
Evaluation of Embryotoxic Potential of Olaquindox and Vitamin A in Micromass Culture and in Rats
Kang, Hwan-Goo ; Ku, Hyun-Ok ; Jeong, Sang-Hee ; Cho, Joon-Hyoung ; Son, Seong-Wan ;
Toxicological Research, volume 26, issue 3, 2010, Pages 209~216
DOI : 10.5487/TR.2010.26.3.209
Limb bud (LB) and central nerve system (CNS) cells were prepared from 12.5 day old pregnant female Crj:CD (SD) rats and treated with olaquindox and vitamin A. Cytotoxicity and inhibition on differentiation were measured in each cell. Three doses of olaquindox (4, 21 and 100 mgkg), and 0.2 and 75 mg/kg of vitamin A were administered to pregnant rat for 11 days from
values of olaquindox for proliferation and differentiation in CNS cell were 22.74 and
and 79.34 and
in LB cell and those values of vitamin A were 8.13 and
in CNS cell and 0.81 and
in LB cell, respectively. Mean body weights of pregnant rats were decreased at high dose of olaquindox (110 mg/kg) but relative ovary weight, number of corpus lutea, and number of implantation were not changed. Resorption and dead fetus were increased at high dose of olaquindox, and relative ovary weight, the number of corpus lutea and implantation, and sex ratio of male to female were not significantly changed in all dose of olaquindox. Mean fetal and placenta weights were significantly (p < 0.01) decreased in rats of high group. Seven fetuses out of 103 showed external anomaly like bent tail, and 10 out of 114 fetuses showed visceral anomalies at high group. The ossification of sternebrae and metacarpals were significantly (p < 0.01) increased by low and middle dose of olaquindox but it was significantly (p < 0.01) prohibited by high dose of olaquindox. In rats treated with vitamin A, the resorption and dead fetus were increased by high dose. Mean fetal weights were significantly (p < 0.01) increased by low dose but significantly (p < 0.01) decreased by high dose. Thirty four fetuses out of 52 showed external anomaly; bent tail (1), cranioarchschisis (14), exencephaly (14), dome shaped head (22), anophthalmia (15), brcahynathia (10) and others (19). Forty five fetuses out of 52 showed soft tissue anomaly; cleft palate (42/52) and anophthalmia (22/52) by high dose of vitamin A. Sixty one fetuses out of 61 (85.2%) showed skull anomaly; defect of frontal, partial and occipital bone (21/61), defect of palatine bone (52/61) and others (50/61). In summary, we support that vitamin A is strong teratogen based on our micromass and in vivo data, and olaquindox has a weak teratogenic potential in LB cell but not in CNS cell. We provide the in vivo evidence that a high dose of olaquindox could have weak embryotoxic potential in rats.
Dose-response Effects of Bleomycin on Inflammation and Pulmonary Fibrosis in Mice
Kim, Soo-Nam ; Lee, Jin-Soo ; Yang, Hyo-Seon ; Cho, Jae-Woo ; Kwon, Soon-Jin ; Kim, Young-Beom ; Her, Jeong-Doo ; Cho, Kyu-Hyuk ; Song, Chang-Woo ; Lee, Kyu-Hong ;
Toxicological Research, volume 26, issue 3, 2010, Pages 217~222
DOI : 10.5487/TR.2010.26.3.217
Many studies have reported that bleomycin, anti-cancer drug, induces pulmonary fibrosis as a side effect. However, few investigations have focused on the dose-response effects of bleomycin on pulmonary fibrosis. Therefore, in the present study, we investigated the effects of different doses of bleomycin in male mice. ICR mice were given 3 consecutive doses of bleomycin: 1, 2, or 4 mg/kg in bleomycin-treated (BT) groups and saline only in vehicle control (VC) groups. The animals were sacrificed at 7 and 24 days postinstillation. The severity of pulmonary fibrosis was evaluated according to inflammatory cell count and lactate dehydrogenase (LDH) activity in the broncho alveolar lavage fluid (BALF), and lung tissues were histologically evaluated after hematoxylin and eosin (H&E), and Masson`s trichrome staining. BT groups exhibited changed cellular profiles in BAL fluid compared to the VC group, which had an increased number of total cells, neutrophils, and lymphocytes and a modest increase in the number of macrophages at 7 days post-bleomycin instillation. Moreover, BT groups showed a dose-dependent increase in LDH levels and inflammatory cell counts. However, at 24 days after treatment, collagen deposition, interstitial thickening, and granulomatous lesions were observed in the alveolar spaces in addition to a decrease in inflammatory cells. These results indicate that pulmonary fibrosis induced by 4 mg/kg bleomycin was more severe than that induced by 1 or 2 mg/kg. These data will be utilized in experimental animal models and as basic data to evaluate therapeutic candidates through non-invasive monitoring using the pulmonary fibrosis mouse model established in this study.
General Pharmacology of Artesunate, a Commonly used Antimalarial Drug: Effects on Central Nervous, Cardiovascular, and Respiratory System
Lee, Hyang-Ae ; Kim, Ki-Suk ; Kim, Eun-Joo ;
Toxicological Research, volume 26, issue 3, 2010, Pages 223~232
DOI : 10.5487/TR.2010.26.3.223
Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR), and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial). Thus, it can be concluded that artesunate is safe at clinical therapeutic doses.
Assay of In Vivo Chromium with a Hollow-fiber Dialysis Sensor
Ly, Suw-Young ; Yoo, Hai-Soo ; Jung, Min-Ki ; Ko, Kwang-Hee ; Kim, Byung-Jin ; Lee, Ki-Chul ; Choi, Byung-Min ;
Toxicological Research, volume 26, issue 3, 2010, Pages 233~236
DOI : 10.5487/TR.2010.26.3.233
The analytical in vivo chromium ion was searched for using a voltammetric hollow-fiber dialysis sensor via square wave stripping voltammetry (SW), cyclic voltammetry (CV), and chronoamperometry. Under optimum parameters, the analytical results indicated linear working ranges of 50~400 mg/l CV and
SW within a 30-sec accumulation time. The analytical detection limit (S/N) was
. The developed method can be applied to in vivo tissues and in ex vivo toxicity assay, as well as to other materials that require chromium analysis.