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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 23, Issue 4 - Dec 2007
Volume 23, Issue 3 - Sep 2007
Volume 23, Issue 2 - Jun 2007
Volume 23, Issue 1 - Mar 2007
Selecting the target year
Toll-like Receptors in Host Defense and Immune Disorders
Lee, Joo-Y. ;
Toxicological Research, volume 23, issue 2, 2007, Pages 97~105
DOI : 10.5487/TR.2007.23.2.097
Toll-like receptors (TLRs) playa crucial role in initiating and regulating innate and adaptive immune responses by detecting invading microbial pathogens. TLRs can also respond to non-microbial molecules derived from damaged tissue. Accumulating evidence suggests that deregulation of TLRs results in the dysfunction of immune system and ultimately increases the risk of many immune and inflammatory diseases including infectious diseases, allergy, and autoimmune diseases. Therefore, understanding how the immune system is controlled by TLRs will provide new insight to find the way to prevent or treat infectious diseases and immune disorders.
Adult Neurogenesis in Insulted Brain
Kim, Byung-Woo ; Son, Hyeon ;
Toxicological Research, volume 23, issue 2, 2007, Pages 107~114
DOI : 10.5487/TR.2007.23.2.107
Although there are some questions about the venues of adult neurogenesis, it is undoubtedly accepted that new neurons are born in adult brains. Adult neurogenesis is regulated by a wide array of factors. Insults harmful to brain, such as neurodegenerative diseases, seizure, ischemia and exposure to drugs of abuse, are intricately related to adult neurogenesis. Whereas neurodegenerative diseases are characterized by death or functional loss of specific neurons, recent studies report that they can be accompanied by neurogenesis. In addition, alcohol and drugs of abuse which have been reputed to cause irreversible damage to brain can also generate newly born cells in adult brain. As yet, however, we have little knowledge of the functional significance and roles of adult neurogenesis under pathological settings, not to mention under physiological settings. Accordingly, in this review we briefly summarize the results of studies which focus on adult neurogenesis in insulted brain, instead of trying to draw hurried conclusion regarding the relationship between adult neurogenesis and brain insults.
Suggestions for Outcome-Oriented R&D Activity in Terms of Intellectual Property Management
Kim, Seung-Kun ; Ko, Myong-Suk ;
Toxicological Research, volume 23, issue 2, 2007, Pages 115~121
DOI : 10.5487/TR.2007.23.2.115
Biotechnology is often described as the 'exploitation of biological processes for industrial purposes'. The last twenty years have seen phenomenal growth in this industry. The 21 century promises to see further advances in the field. However, since the cost of research is high, and the potential returns are linked to exclusivity, intellectual property protection is critical to this burgeoning industry. Without protection such investments in R&D would not be made and, the benefit that BT-related development are expected to bring, would not occur. BT industry are eager for high technology, and the technology must be transferred to a corporation from a research organization. In order to be successful, it is important that scientist must be directed toward R&D outcome beyond performance assessment. The process to gain a outcome involves multiple steps to turn the idea into the profit, and intellectual property issues are considered into the critical factors to affect the quality of R&D. The management of Intellectual property is very important in R&D. However, According to the survey conducted by KIIP (Korea Institute of Intellectual Property) and KOSEF (Korea Science and Engineering Foundation) in 2006, it is estimated the ability to treat Intellectual property is not sufficient because 82.5% of the respondents have not received an education. Governmental Support is needed to prompt systematically the ability of intellectual property management through education and consulting.
Inhibition of the Induction of Nitric Oxide Synthase by Kobusin
Kim, Sang-Kyum ; Pokharel, Yuba-Raj ; Kim, Ok ; Woo, Eun-Rhan ; Kang, Keon-Wook ;
Toxicological Research, volume 23, issue 2, 2007, Pages 123~126
DOI : 10.5487/TR.2007.23.2.123
We isolated a lignan, kobusin from Geranium thunbergii and studied its effect on the expression of inducible nitric oxide synthase (iNOS) gene in a monocyte/macrophage cell line, RAW264.7 cells. Kobusin inhibited lipopolysaccharide (LPS)-stimulated NO production and the expression of iNOS in a concentration-dependent manner. To identify the mechanistic basis for its inhibition of iNOS induction, we examined the effect of kobusin on both the luciferase reporter activity using
minimal promoter and the nuclear translocation of p65. Kobusin suppressed the reporter gene activity and the LPS-induced movement of p65 in to nucleus.
activation is controlled by the phosphorylation and subsequent degradation of
, and in the present study, we found that
phosphorylation was also inhibited by kobusin. Our findings indicate that kobusin may provide a developmental basis for an agent against inflammatory diseases.
Repression of γ-Glutamylcysteine Synthetase and Glutathione S-Transferases by Metformin, an Anti-diabetic Agent, in H4IIE Rat Hepatocytes
Bae, Eun-Ju ; Cho, Min-Joo ; Kim, Sang-Geon ;
Toxicological Research, volume 23, issue 2, 2007, Pages 127~133
DOI : 10.5487/TR.2007.23.2.127
Metformin is a drug used to lower blood sugar levels in patients with type 2 diabetes via activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). The primary objective of this study was to investigate whether metformin at the pharmacologically effective concentrations affects the expressions of
-glutamylcysteine synthetase and phase II antioxidant genes in the H4IIE cell. Treatment of the cells with either metformin or 5-aminoimidazole-4-carboxamide riboside (AICAR) abrogated tert-butylhydroxyquinone (t-BHQ) induction of
-glutamylcysteine synthetase, a rate limiting enzyme of GSH synthesis. The ability of t-BHQ to induce glutathione S-transferases (GSTs), a major class of phase II detoxifying enzymes that playa critical role in protecting cells from oxidative stress or electrophiles, was also inhibited by the agents. Transcriptional gene repression by metformin was verified by the GSTA2 promoter luciferase assay. Moreover, either metformin or AICAR treatment significantly decreased t-BHQ-dependent induction of other GSTs (i.e.,
forms). Taken together, our data indicate that metformin treatment may result in the repression of
-glutamylcysteine synthetase and glutathione S-transferase genes possibly via AMPK activation.
Effects of Formononetin on the Aryl Hydrocarbon Receptor and 7,12-Dimethylbenz[a]anthracene-induced Cytochrome P450 1A1 in MCF-7 Human Breast Carcinoma Cells
Han, Eun-Hee ; Jeong, Tae-Cheon ; Jeong, Hye-Gwang ;
Toxicological Research, volume 23, issue 2, 2007, Pages 135~142
DOI : 10.5487/TR.2007.23.2.135
Formononetin is an isoflavonoid phytoestrogen found in certain foodstuffs such as soy and red clover. In this study, we examined the action of formononetin with the carcinogen activation pathway mediated through the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with formononetin alone caused the accumulation of CYP1A1 mRNA as well as elevation in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. However, a concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and formononetin markedly reduced both the DMBA-inducible EROD activity and CYP1A1 mRNA level. Under the same conditions, formononetin inhibited the DMBA-induced AhR transactivation, as shown by reporter gene analysis using a xenobiotic responsive element (XRE). Additionally, formononetin inhibited both DMBA-inducible nuclear localization of the aryl hydrocarbon receptor (AhR) and metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. Furthermore, formononetin competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. These results suggest that formononetin might be considered as a natural ligand to bind on AhR and consequently produces a potent protective effect against DMBA-induced genotoxicity. Therefore, that's the potential to act as a chemopreventive agent that is related to its effect on AhR pathway as antagonist/agonist.
Evaluation of Antioxidant Activity of Sugar Alcohols Using TOSC (Total Oxy-radical Scavenging Capacity) Assay
Kang, Keon-Wook ; Kwak, Sang-Hoon ; Yun, Sei-Young ; Kim, Sang-Kyum ;
Toxicological Research, volume 23, issue 2, 2007, Pages 143~150
DOI : 10.5487/TR.2007.23.2.143
Although animal and epidemiological studies have suggested oxidative stress as an etiological factor in pathogenesis including cancer, inflammation, sepsis, fibrosis, cardiovascularlneurodegenerative diseases and aging-related disorders, conflicting results have been obtained in clinical trial with antioxidants. The reason for this discrepancy remains unknown but may be due, in part, to the lack of a validated assay system for evaluating antioxidant capacity. The antioxidant activity of a series of sugar alcohols against peroxyl radicals, hydroxyl radicals and peroxynitrites was determined by the total oxy-radical scavenging capacity (TOSC) assay and cell-based assay using H4IIE cells. Specific TOSC values calculated from the slope of the linear regression for erythritol, xylitol, sorbitol or mannitol against peroxyl radicals was
TOSC/mM, respectively. Specific TOSC values for erythritol, xylitol, sorbitol or mannitol against peroxynitrite was
TOSC/mM, respectively. These results suggest that oxy-radical scavenging capacity is dependent on the number of aliphatic hydroxyl group in sugar alcohols of monosaccharide. Tert-butylhydroperoxide (t-BHP)-induced cell toxicity determined by MTT assay was marginally attenuated by 10 mM erythritol, but completely inhibited by 10 mM xylitol, 2 mM sorbitol or 0.75 mM maltitol, a disaccharide alcohol. Oxidative stress markers, such as glutathione (GSH) and malondial-dehyde (MDA) levels, were measured in t-BHP-treated cells using HPLC equipped with a fluorescence detector and a reverse phase column. Erythritol did not change the levels of GSH and MDA in H411E cells treated with t-BHP. The t-BHP-induced changes in cellular GSH and MDA levels were ameliorated by 10 mM xylitol and completely blocked by 10 mM sorbitol and maltitol. These results indicate that sugar alcohols protect cells against oxidative stress via scavenging oxy-radical and suggest that TOSC assay in conjunction with cell-based assay is a valid method for evaluating antioxidant capacity of natural and synthetic chemicals.
Teratogenicity Study of tert-Butyl Acetate in Rats
Ahn, Tai-Hwan ; Yang, Young-Su ; Lee, Jong-Chan ; Kang, Seong-Soo ; Bae, Chun-Sik ; Kim, Sung-Ho ; Kim, Jong-Choon ; Kim, Hyeon-Yeong ; Chung, Yong-Hyun ;
Toxicological Research, volume 23, issue 2, 2007, Pages 151~158
DOI : 10.5487/TR.2007.23.2.151
tert-Butyl acetate is an organic solvent used for coatings, industrial cleaning, and surface treatment applications. This study investigated the potential adverse effects of tert-butyl acetate on pregnant dams and embryo-fetal development after maternal exposure on gestational days 6 through 19 in rats. The test chemical was administered to pregnant rats by gavage at dose levels of 0, 500, 1,000, 1,500, and 2,000 mg/kg/day. All dams were subjected to a caesarean section on day 20 of gestation and their fetuses were examined for any external, visceral, and skeletal abnormalities. At 2,000 mg/kg, treatment-related clinical signs, including piloerection, abnormal gait, decreased locomotor activity, loss of fur, reddish tear, anorexia, nasal discharge, vocalization and coma, were observed in a dose-dependent manner. All dams died between the 2nd day and 5th day of treatment due to a severe systemic toxicity. At 1,500 mg/kg, minimal maternal toxicity including an increase in the incidence of decreased locomotor activity and loss of fur, and an increase in the weights of adrenal glands and liver was observed. On the contrary, no significant adverse effect on the embryo-fetal development was detected. There were no adverse effects on either pregnant dams or embryo-fetal development at <1,000 mg/kg. These results show that a 14-day repeated oral dose of tert-butyl acetate in rats caused a minimal maternal toxicity including increases in the incidence of clinical signs and the weights of adrenal glands and liver, but no embryotoxicity and teratogenicity at 1,500 mg/kg/day. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) of tert-butyl acetate is estimated to be 1,000 mg/kg per day for dams and 1,500 mg/kg per day for embryo-fetal development.
Toxicity Screening After Single Dose of a Newly Developed Oral Heparin Derivative in Male Cynomolgus Monkeys
Kim, Choong-Yong ; Kim, Sang-Kyoon ; Woo, Young-Ah ; Jeong, Eun-Ju ; Han, Su-Cheol ; Heo, Jeong-Doo ; Park, Kui-Lea ; Byun, Young-Ro ;
Toxicological Research, volume 23, issue 2, 2007, Pages 159~164
DOI : 10.5487/TR.2007.23.2.159
Toxicity screening of a newly developed oral heparin derivative were carried out in 6 male cynomolgus monkeys (Macaca fascicularis), composed of a treatment group and vehicle control group. A newly orally active heparin derivative, developed by Seoul National University, was once given to treatment group at dose of 500 mg/kg. A treatment group did not show any change in body weights, hematological parameters including platelet-related varivables (platelet, PDW, PCT, MPV) and serum biochemical parameters (e.g., AST, ALT, BUN, etc.) for 2 weeks compared with those of vehicle control group. We also confirmed the maximum plasma concentration (Cmax, 1.73 IU/ml) and the time (Tmax, 1 hr) to reach Cmax. The present study will be valuable in the proper interpretation for nonclinical study using cynomolgus monkeys in the development of new drug of heparin derivative.
Antigastritic Effect of Carbenoxolone Disodium from Glycyrrhizae Radix
Cho, So-Yean ; Lee, Seung-Ho ; Choi, Ji-Young ; Myoung, Shin-Eun ; Kang, Sam-Sik ; Jeong, Jeong-Suk ; Jeong, Choon-Sik ;
Toxicological Research, volume 23, issue 2, 2007, Pages 165~172
DOI : 10.5487/TR.2007.23.2.165
Glycyrrhizae Radix, the dried roots of Glycyrrhiza glabra or Glycyrrhiza uralensis Fischer(Legumino-sae), has been used as a medicine for treatment of imflammation, arthritis, respiratory ailment, skin diseases and liver problems. The purpose of this study was to examine the effect of 70% ethanol extract, 18-
-glycyrrhetinic acid, glycyrol and carbenoxolone disodium from Glycyrrhizae Radix on gastritis and gastric cancer. Using these materials, we tested antibacterial activity against Helicobacter pylori, antigastritic activity for HCI-ethanol-induced gastric lesion and the pylorus ligated gastric secretion with rats, and cell viability in gastric cancer cell. 18-
-glycyrrhetinic acid and carbenoxolone disodium decreased the volume of gastric secretion and acid output in pylorus ligated rats. Also, carbenoxolone disodium had a strong effect of antibacterial activity on H. pylori. In addition 18-
-glycyrrhetinic acid and glycyrol reduced cell viability in human gastric cancer cells(AGS and SNU638 cell) in dose-dependent manner. The reduction of total acid output and gastric secretion as well as the anti-bacterial activity against H. pylori might account for the antigastritic effects of carbenoxolone disodium.
Characterization of Test Substance in the GLP
Lee, Eun-Jung ; Song, Kyung-Seuk ; Yu, Il-Je ;
Toxicological Research, volume 23, issue 2, 2007, Pages 173~177
DOI : 10.5487/TR.2007.23.2.173
The GLP contains specific language concerning characterization of the test, control and reference substances used in toxicity studies. This paper will describe and discuss what types of documents are required to support test/reference substance characterization under GLP system. The purpose of this article is to present an overview of data needed in the characterization package that will adequately define the substance. Most sponsors use a certificate of analysis (COA) to communicate the test sub-stance characterization status information to the contracting research organizations. The COA should provide the test
characterization results, substance storage requirements, expiration dates, verification of the collection of the retention sample, archival location of the data to support the characterization and GLP compliance status of the characterization.
Investigation of International Nonproprietary Names (INN) Nomenclature System For Biotechnological Products
Kim, Eun-Sook ; Song, Jae-In ; Moon, A-Ree ;
Toxicological Research, volume 23, issue 2, 2007, Pages 179~187
DOI : 10.5487/TR.2007.23.2.179
An International Nonproprietary Name (INN) identifies a pharmaceutical substance or active pharmaceutical ingredient by a unique name that is globally recognized and is of public property. Also known as the generic or common names, the official INNs are provided by national and international nomenclature bodies such as United States Adopted Names (USAN), British Approved Names (BAN), Japanese Accepted Names (JAN) and World Health Organization (WHO). Due to the increasing interest on the development of biotechnological products in Korea, needs for the formulated nomenclature body in Korea are arising for systemic management of newly developed biotechnological products. This study investigated and analyzed nomenclature systems and procedures for the selection of recommended INN for biotechnological products in WHO, USAN and JAN. Based on these documents from advanced countries, we suggested a Korean INN nomenclature organization named KAN (Korean Adopted Names or Korean Agreed Names). Composition and roles of KAN and KAN expert committee and a working process for INN selection/approval were also proposed. Taken together, this study provides a detailed information on INN system recognized worldwide and suggests guidelines for establishment of INN nomenclature system for biotechnological products in Korea.