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The Korean Society of Toxicology
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Volume 32, Issue 3 - Jul 2016
Volume 32, Issue 2 - Apr 2016
Volume 32, Issue 1 - Jan 2016
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Cancer Activation and Polymorphisms of Human Cytochrome P450 1B1
Chun, Young-Jin ; Kim, Donghak ;
Toxicological Research, volume 32, issue 2, 2016, Pages 89~93
DOI : 10.5487/TR.2016.32.2.089
Human cytochrome P450 enzymes (P450s, CYPs) are major oxidative catalysts that metabolize various xenobiotic and endogenous compounds. Many carcinogens induce cancer only after metabolic activation and P450 enzymes play an important role in this phenomenon. P450 1B1 mediates bioactivation of many procarcinogenic chemicals and carcinogenic estrogen. It catalyzes the oxidation reaction of polycyclic aromatic carbons, heterocyclic and aromatic amines, and the 4-hydroxylation reaction of
-estradiol. Enhanced expression of P450 1B1 promotes cancer cell proliferation and metastasis. There are at least 25 polymorphic variants of P450 1B1 and some of these have been reported to be associated with eye diseases. In addition, P450 1B1 polymorphisms can greatly affect the metabolic activation of many procarcinogenic compounds. It is necessary to understand the relationship between metabolic activation of such substances and P450 1B1 polymorphisms in order to develop rational strategies for the prevention of its toxic effect on human health.
Bio-Inspired Green Nanoparticles: Synthesis, Mechanism, and Antibacterial Application
Velusamy, Palaniyandi ; Kumar, Govindarajan Venkat ; Jeyanthi, Venkadapathi ; Das, Jayabrata ; Pachaiappan, Raman ;
Toxicological Research, volume 32, issue 2, 2016, Pages 95~102
DOI : 10.5487/TR.2016.32.2.095
In the recent years, noble nanoparticles have attracted and emerged in the field of biology, medicine and electronics due to their incredible applications. There were several methods have been used for synthesis of nanoparticles such as toxic chemicals and high energy physical procedures. To overcome these, biological method has been used for the synthesis of various metal nanoparticles. Among the nanoparticles, silver nanoparticles (AgNPs) have received much attention in various fields, such as antimicrobial activity, therapeutics, bio-molecular detection, silver nanocoated medical devices and optical receptor. Moreover, the biological approach, in particular the usage of natural organisms has offered a reliable, simple, nontoxic and environmental friendly method. Hence, the current article is focused on the biological synthesis of silver nanoparticles and their application in the biomedical field.
Hair Growth-Promoting Effects of Lavender Oil in C57BL/6 Mice
Lee, Boo Hyeong ; Lee, Jae Soon ; Kim, Young Chul ;
Toxicological Research, volume 32, issue 2, 2016, Pages 103~108
DOI : 10.5487/TR.2016.32.2.103
The purpose of this study was to determine the hair growth effects of lavender oil (LO) in female C57BL/6 mice. The experimental animals were divided into a normal group (N: saline), a vehicle control group (VC: jojoba oil), a positive control group (PC: 3% minoxidil), experimental group 1 (E1: 3% LO), and experimental group 2 (E2: 5% LO). Test compound solutions were topically applied to the backs of the mice (
per application), once per day, 5 times a week, for 4 weeks. The changes in hair follicle number, dermal thickness, and hair follicle depth were observed in skin tissues stained with hematoxylin and eosin, and the number of mast cells was measured in the dermal and hypodermal layers stained with toluidine blue. PC, E1, and E2 groups showed a significantly increased number of hair follicles, deepened hair follicle depth, and thickened dermal layer, along with a significantly decreased number of mast cells compared to the N group. These results indicated that LO has a marked hair growth-promoting effect, as observed morphologically and histologically. There was no significant difference in the weight of the thymus among the groups. However, both absolute and relative weights of the spleen were significantly higher in the PC group than in the N, VC, E1, or E2 group at week 4. Thus, LO could be practically applied as a hair growth-promoting agent.
External Application of Apo-9`-fucoxanthinone, Isolated from Sargassum muticum, Suppresses Inflammatory Responses in a Mouse Model of Atopic Dermatitis
Han, Sang-Chul ; Kang, Na-Jin ; Yoon, Weon-Jong ; Kim, Sejin ; Na, Min-Chull ; Koh, Young-Sang ; Hyun, Jin-Won ; Lee, Nam-Ho ; Ko, Mi-Hee ; Kang, Hee-Kyoung ; Yoo, Eun-Sook ;
Toxicological Research, volume 32, issue 2, 2016, Pages 109~114
DOI : 10.5487/TR.2016.32.2.109
Allergic skin inflammation such as atopic dermatitis is characterized by skin barrier dysfunction, edema, and infiltration with various inflammatory cells. The anti-inflammatory effects of Apo-9`-fucoxanthinone, isolated from Sargassum muticum, have been described in many diseases, but the mechanism by which it modulates the immune system is poorly understood. In this study, the ability of Apo-9`-fucoxanthinone to suppress allergic reactions was investigated using a mouse model of atopic dermatitis. The Apo-9`-fucoxanthinone-treated group showed significantly decreased immunoglobulin E in serum. Also, Apo-9`-fucoxanthinone treatment resulted in a smaller lymph node size with reduced the thickness and length compared to the induction group. In addition, Apo-9`-fucoxanthinone inhibited the expression of interleukin-4, interferon-gamma and tumor necrosis factor-alpha by phorbol 12-myristate 13-acetate and ionomycin-stimulated lymphocytes. These results suggest that Apo-9`-fucoxanthinone may be a useful therapeutic strategy for treating chronic inflammatory diseases.
Modulation of Apoptosis and Differentiation by the Treatment of Sulfasalazine in Rabbit Articular Chondrocytes
Lee, Won Kil ; Kang, Jin Seok ;
Toxicological Research, volume 32, issue 2, 2016, Pages 115~121
DOI : 10.5487/TR.2016.32.2.115
This study was conducted to examine the cellular regulatory mechanisms of sulfasalazine (SSZ) in rabbit articular chondrocytes treated with sodium nitroprusside (SNP). Cell phenotype was determined, and the MTT assay, Western blot analysis and immunofluorescence staining of type II collagen was performed in control, SNP-treated and SNP plus SSZ (
) rabbit articular chondrocytes. Cellular proliferation was decreased significantly in the SNP-treated group compared with that in the control (p < 0.01). SSZ treatment clearly increased the SNP-reduced proliferation levels in a concentration-dependent manner (p < 0.01). SNP treatment induced significant dedifferentiation and inflammation compared with control chondrocytes (p < 0.01). Type II collagen expression levels increased in a concentration-dependent manner in response to SSZ treatment but were unaltered in SNP-treated chondrocytes (p < 0.05 and < 0.01, respectively). Cylooxygenase-2 (COX-2) expression increased in a concentration-dependent manner in response to SSZ treatment but was unaltered in SNP-treated chondrocytes (p < 0.05). Immunofluorescence staining showed that SSZ treatment increased type II collagen expression compared with that in SNP-treated chondrocytes. Furthermore, phosphorylated extracellular regulated kinase (pERK) expression levels were decreased significantly in the SNP-treated group compared with those in control chondrocytes (p < 0.01). Expression levels of pERK increased in a concentration-dependent manner by SSZ but were unaltered in SNP-treated chondrocytes. pp38 kinase expression levels increased in a concentration-dependent manner by SSZ but were unaltered in control chondrocytes (p < 0.01). In summary, SSZ significantly inhibited nitric oxide-induced cell death and dedifferentiation, and regulated extracellular regulated kinases 1 and 2 and p38 kinase in rabbit articular chondrocytes.
Neurobehavioural Changes and Brain Oxidative Stress Induced by Acute Exposure to GSM900 Mobile Phone Radiations in Zebrafish (Danio rerio)
Nirwane, Abhijit ; Sridhar, Vinay ; Majumdar, Anuradha ;
Toxicological Research, volume 32, issue 2, 2016, Pages 123~132
DOI : 10.5487/TR.2016.32.2.123
The impact of mobile phone (MP) radiation on the brain is of specific interest to the scientific community and warrants investigations, as MP is held close to the head. Studies on humans and rodents revealed hazards MP radiation associated such as brain tumors, impairment in cognition, hearing etc. Melatonin (MT) is an important modulator of CNS functioning and is a neural antioxidant hormone. Zebrafish has emerged as a popular model organism for CNS studies. Herein, we evaluated the impact of GSM900MP (GSM900MP) radiation exposure daily for 1 hr for 14 days with the SAR of 1.34W/Kg on neurobehavioral and oxidative stress parameters in zebrafish. Our study revealed that, GSM900MP radiation exposure, significantly decreased time spent near social stimulus zone and increased total distance travelled, in social interaction test. In the novel tank dive test, the GSM900MP radiation exposure elicited anxiety as revealed by significantly increased time spent in bottom half; freezing bouts and duration and decreased distance travelled, average velocity, and number of entries to upper half of the tank. Exposed zebrafish spent less time in the novel arm of the Y-Maze, corroborating significant impairment in learning as compared to the control group. Exposure decreased superoxide dismutase (SOD), catalase (CAT) activities whereas, increased levels of reduced glutathione (GSH) and lipid peroxidation (LPO) was encountered showing compromised antioxidant defense. Treatment with MT significantly reversed the above neurobehavioral and oxidative derangements induced by GSM900MP radiation exposure. This study traced GSM900MP radiation exposure induced neurobehavioral aberrations and alterations in brain oxidative status. Furthermore, MT proved to be a promising therapeutic candidate in ameliorating such outcomes in zebrafish.
Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver
Heidari, Reza ; Esmailie, Neda ; Azarpira, Negar ; Najibi, Asma ; Niknahad, Hossein ;
Toxicological Research, volume 32, issue 2, 2016, Pages 133~140
DOI : 10.5487/TR.2016.32.2.133
Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC (
), DTT (
), Vitamin C (
), or vitamin E (
) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.
Melanogenesis-Promoting Effects of Rhynchosia nulubilis and Rhynchosia volubilis Ethanol Extracts in Melan-a Cells
Hong, Seong Hee ; Sim, Mi Ja ; Kim, Young Chul ;
Toxicological Research, volume 32, issue 2, 2016, Pages 141~147
DOI : 10.5487/TR.2016.32.2.141
We evaluated the antioxidant activity and melanogenic effects of black soybean ethanol extracts, including Rhynchosia nulubilis bean ethanol extract (RNBEE), R. nulubilis leaf ethanol extract (RNLEE), R. volubilis bean ethanol extract (RVBEE), and R. volubilis leaf ethanol extract (RVLEE). The total polyphenol contents of RNBEE, RNLEE, RVBEE, and RVLEE were 16.0, 57.7, 365.9, and 260.1 mg/g, respectively. The total flavonoid contents of RNBEE, RNLEE, RVBEE, and RVLEE were 40.4, 91.7, 84.7, and 216.5 mg/g, respectively. The electron-donating abilities of RNBEE, RNLEE, RVBEE, and RVLEE at
were 32.4%, 12.7%, 83.5%, and 84.5%, respectively. RNBEE, RNLEE, RVBEE, and RVLEE at
significantly increased (p < 0.01) melanin contents by 30.4%, 32.1%, 35.5%, and 37.4%, respectively, compared to that of the control. RNBEE, RNLEE, RVBEE, and RVLEE at
significantly increased (p < 0.01) intracellular tyrosinase activity by 18.4%, 21.8%, 21.5%, and 21.1%, respectively, compared to that of the control. These results demonstrated that black soybean ethanol extracts promote melanogenesis in melan-a cells. Among the black soybean ethanol extracts, R. volubilis was found to be more effective than R. nulubilis, and leaf extract was found to be more effective than bean extract. The potential mechanism underlying the hyperpigmentation effects of black soybeans is the promotion of tyrosinase activity.
A Probiotic Preparation Alleviates Atopic Dermatitis-Like Skin Lesions in Murine Models
Kim, Min-Soo ; Kim, Jin-Eung ; Yoon, Yeo-Sang ; Seo, Jae-Gu ; Chung, Myung-Jun ; Yum, Do-Young ;
Toxicological Research, volume 32, issue 2, 2016, Pages 149~158
DOI : 10.5487/TR.2016.32.2.149
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex etiology that encompasses immunologic responses. AD is frequently associated with elevated immunoglobulin (Ig) E levels, and common environmental factors contribute to its pathogenesis. Several recent studies have documented the role of specific lactic acid bacteria in the treatment and prevention of AD in humans and mice. In this study, the efficacy of Duolac ATP, a probiotic preparation, was determined in a mouse model with AD-like skin lesions. Alterations in the cytokine levels and histological staining suggested the alleviation of AD. The in vivo test showed that T helper (Th)2 cytokines, IgE, interleukin (IL)-4, and IL-5, were significantly downregulated, whereas Th1 cytokines, IL-12p40 and interferon (IFN)-
, were upregulated in all groups of mice treated with Duolac ATP compared to that observed in the group of mice treated with 1-chloro-2,4-dinitrobenzene (DNCB) alone. Moreover, the scratch score decreased in all mice treated with Duolac ATP. Staining of the dorsal area of the mice in each group with hematoxylin and eosin and toluidine blue further confirmed the alleviation of AD in mice orally treated with Duolac ATP. These results suggest that Duolac ATP inhibits the development of AD-like skin lesions in NC/Nga mice by suppressing the Th2 cell response and increasing the Th1 cell response. Thus, Duolac ATP is beneficial and effective for the treatment of AD-like skin lesions.
Oral Toxicity Study and Skin Sensitization Test of a Cricket
Ryu, Hyeon Yeol ; Lee, Somin ; Ahn, Kyu Sup ; Kim, Hye Jin ; Lee, Sang Sik ; Ko, Hyuk Ju ; Lee, Jin Kyu ; Cho, Myung-Haing ; Ahn, Mi Young ; Kim, Eun Mi ; Lim, Jeong Ho ; Song, Kyung Seuk ;
Toxicological Research, volume 32, issue 2, 2016, Pages 159~173
DOI : 10.5487/TR.2016.32.2.159
Crickets have been attracting considerable interest in the field of nutrition and toxicology due to the global exhaustion of food resulting from a growing population. The cricket is normally eaten in several countries after roasting, similar to the grasshopper; however, safety evaluation data on cricket powder is limited. Here, we performed general toxicity studies of cricket powder including a single, 2-week repeated dose range evaluation test, a 13-week repeated oral dose toxicity test in Sprague-Dawley rats, a single oral dose toxicity test in Beagle dogs, and a skin sensitization test in guinea pigs following the Organization for Economic Cooperation and Development test guidelines 406 and 408 in addition to Good Laboratory Practice. To investigate the NOAEL and target organs of cricket powder, Sprague-Dawley rats were allocated to 4 groups: vehicle control, 1,250 mg/kg, 2,500 mg/kg, 5,000 mg/kg dose test groups and cricket powder was administered over 13 weeks after single dose and dose range finding studies in rats based on the results of the single oral administration toxicity study in rats and Beagle dogs. The results of the study showed that the NOAEL of cricket powder was over 5,000 mg/kg for both sexes of rats without adverse effects in a 13-week repeated oral toxicity study and there was no skin hypersensitivity reaction. Therefore, our results reveal that crickets can be widely used as a new substitute food or nutrient resource.
Erratum to "Evaluation of Genotoxicity and 28-day Oral Dose Toxicityon Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)" [Toxicol. Res. 30 (2014) 121-130]
Han, So-Ri ; Yun, Eun-Young ; Kim, Ji-Young ; Hwang, Jae Sam ; Jeong, Eun Ju ; Moon, Kyoung-Sik ;
Toxicological Research, volume 32, issue 2, 2016, Pages 175~175
DOI : 10.5487/TR.2016.32.2.175