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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 30, Issue 4 - Dec 2014
Volume 30, Issue 3 - Sep 2014
Volume 30, Issue 2 - Jun 2014
Volume 30, Issue 1 - Mar 2014
Selecting the target year
A Panoramic Overview of Mitochondria and Mitochondrial Redox Biology
Kim, Aekyong ;
Toxicological Research, volume 30, issue 4, 2014, Pages 221~234
DOI : 10.5487/TR.2014.30.4.221
Mitochondria dysfunction was first described in the 1960s. However, the extent and mechanisms of mitochondria dysfunction's role in cellular physiology and pathology has only recently begun to be appreciated. To adequately evaluate mitochondria-mediated toxicity, it is not only necessary to understand mitochondria biology, but discerning mitochondrial redox biology is also essential. The latter is intricately tied to mitochondrial bioenergetics. Mitochondrial free radicals, antioxidants, and antioxidant enzymes are players in mitochondrial redox biology. This review will provide an across-the-board, albeit not in-depth, overview of mitochondria biology and mitochondrial redox biology. With accumulating knowledge on mitochondria biology and mitochondrial redox biology, we may devise experimental methods with adequate sensitivity and specificity to evaluate mitochondrial toxicity, especially in vivo in living organisms, in the near future.
Mitochondrial DNA Somatic Mutation in Cancer
Kim, Aekyong ;
Toxicological Research, volume 30, issue 4, 2014, Pages 235~242
DOI : 10.5487/TR.2014.30.4.235
Cancer cells are known to drastically alter cellular energy metabolism. The Warburg effect has been known for over 80 years as pertaining cancer-specific aerobic glycolysis. As underlying molecular mechanisms are elucidated so that cancer cells alter the cellular energy metabolism for their advantage, the significance of the modulation of metabolic profiles is gaining attention. Now, metabolic reprogramming is becoming an emerging hallmark of cancer. Therapeutic agents that target cancer energy metabolism are under intensive investigation, but these investigations are mostly focused on the cytosolic glycolytic processes. Although mitochondrial oxidative phosphorylation is an integral part of cellular energy metabolism, until recently, it has been regarded as an auxiliary to cytosolic glycolytic processes in cancer energy metabolism. In this review, we will discuss the importance of mitochondrial respiration in the metabolic reprogramming of cancer, in addition to discussing the justification for using mitochondrial DNA somatic mutation as metabolic determinants for cancer sensitivity in glucose limitation.
Mitophagy: Therapeutic Potentials for Liver Disease and Beyond
Lee, Sooyeon ; Kim, Jae-Sung ;
Toxicological Research, volume 30, issue 4, 2014, Pages 243~250
DOI : 10.5487/TR.2014.30.4.243
Mitochondrial integrity is critical for maintaining proper cellular functions. A key aspect of regulating mitochondrial homeostasis is removing damaged mitochondria through autophagy, a process called mitophagy. Autophagy dysfunction in various disease states can inactivate mitophagy and cause cell death, and defects in mitophagy are becoming increasingly recognized in a wide range of diseases from liver injuries to neurodegenerative diseases. Here we highlight our current knowledge on the mechanisms of mitophagy, and discuss how alterations in mitophagy contribute to disease pathogenesis. We also discuss mitochondrial dynamics and potential interactions between mitochondrial fusion, fission and mitophagy.
Comparison of International Guidelines of Dermal Absorption Tests Used in Pesticides Exposure Assessment for Operators
So, Jaehwan ; Ahn, Junyoung ; Lee, Tae-Hee ; Park, Kyung-Hun ; Paik, Min-Kyoung ; Jeong, Mihye ; Cho, Myung-Haing ; Jeong, Sang-Hee ;
Toxicological Research, volume 30, issue 4, 2014, Pages 251~260
DOI : 10.5487/TR.2014.30.4.251
The number of farmers who have suffered from non-fatal acute pesticide poisoning has been reported to vary from 5.7% to 86.7% in South Korea since 1975. Absorption through the skin is the main route of exposure to pesticides for farmers who operate with them. Several in vitro tests using the skins of humans or animal and in vivo tests using laboratory animals are introduced for the assessment of human dermal absorption level of pesticides. The objective of this study is to evaluate and compare international guidelines and strategies of dermal absorption assessments and to propose unique approaches for applications into pesticide registration process in our situation. Until present in our situation, pesticide exposure level to operator is determined just using default value of 10 as for skin absorption ratio because of data shortage. Dermal absorption tests are requested to get exposure level of pesticides and to ultimately know the safety of pesticides for operators through the comparison with the value of AOEL. When the exposure level is higher than AOEL, the pesticide cannot be approved. We reviewed the skin absorption test guidelines recommended by OECD, EFSA and EPA. The EPA recommends assessment of skin absorption of pesticides for humans through the TPA which includes all the results of in vitro human and animal and animal in vivo skin absorption studies. OECD and EFSA, employ a tiered approach, which the requirement of further study depends on the results of the former stage study. OECD guidelines accept the analysis of pesticide level absorbed through skin without radioisotope when the recovery using the non-labeled method is within 80~120%. Various factors are reviewed in this study, including the origin of skin (gender, animal species and sites of skin), thickness, temperature and, etc., which can influence the integrity of results.
Transformation of Mouse Liver Cells by Methylcholanthrene Leads to Phenotypic Changes Associated with Epithelial-mesenchymal Transition
Oh, Jiyun ; Kwak, Jae-Hwan ; Kwon, Do-Young ; Kim, A-Young ; Oh, Dal-Seok ; Je, Nam Kyung ; Lee, Jaewon ; Jung, Young-Suk ;
Toxicological Research, volume 30, issue 4, 2014, Pages 261~266
DOI : 10.5487/TR.2014.30.4.261
Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) have been implicated in cancer development and progression. However, the effects of PAHs on carcinogenesis are still poorly understood. Here, we characterized a mouse cancer cell line BNL 1ME A. 7R.1 (1MEA) derived by transformation of non-tumorigenic liver cell line BNL CL.2 (BNL) using 3-methylcholanthrene (3MC), a carcinogenic PAH. RT-PCR and immunoblot analysis were used to determine the expression level of mRNA and proteins, respectively. To determine functionality, cell motility was assessed in vitro using a transwell migration assay. Both mRNA and protein levels of E-cadherin were significantly decreased in 1MEA cells in comparison with BNL cells. While the expression levels of mesenchymal markers and related transcription factors were enhanced in 1MEA cells, which could lead to increase in cell motility. Indeed, we found that 7-day exposure of BNL cells to 3-MC reduced the level of the adhesion molecule and epithelial marker E-cadherin and increased reciprocally the level of the mesenchymal marker vimentin in a dose-dependent manner. Taken together, these results indicate that the process of epithelial-mesenchymal transition (EMT) may be activated during premalignant transformation induced by 3-MC. A mechanism study to elucidate the relation between 3-MC exposure and EMT is underway in our laboratory.
Influence of Lead on Repetitive Behavior and Dopamine Metabolism in a Mouse Model of Iron Overload
Chang, JuOae ; Kueon, Chojin ; Kim, Jonghan ;
Toxicological Research, volume 30, issue 4, 2014, Pages 267~276
DOI : 10.5487/TR.2014.30.4.267
Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity.
Immune Modulation of B. terrestris Worker (a Type of Bumblebee), Extract on CFA-induced Paw Edema in Rats
Ahn, Mi Young ; Kim, Soon Ja ; Han, Jea Woong ; Yoon, Hyung Joo ; Hwang, Jae Sam ; Yun, Eun Young ;
Toxicological Research, volume 30, issue 4, 2014, Pages 277~282
DOI : 10.5487/TR.2014.30.4.277
To develop a composition for enhancing immunity, based on alcohol extracts of the bumblebee as an active ingredient, bumblebee ethanol extracts were evaluated for their protective effect in chronic models of inflammation, adjuvant induced rat arthritis. B. terrestris worker extract (SDIEX) and, B. hypocrita sapporoensis lava and pupa extract (SPDYBEX), significantly decreased paw edema in arthritic rats, at a dose 100 mg/kg, respectively. The cytokine levels related inflammation of COX-2,
, VEGF, and TNF-
, were decreased, compared to positive control, indomethacin (5 mg/kg). Histopathological data demonstrated decreases inflammatory activity, hind paw edema, and repaired hyaline articular cartilage in DRG over a 2 wk administration. HPLC and GC-MS analysis of SDIEX and SPDYBEX revealed the presence of cantharidin.
Anti-wrinkle Effects of Water Extracts of Teas in Hairless Mouse
Lee, Kyung Ok ; Kim, Sang Nam ; Kim, Young Chul ;
Toxicological Research, volume 30, issue 4, 2014, Pages 283~289
DOI : 10.5487/TR.2014.30.4.283
Tea flavonoids and polyphenols are well known for their extraordinary antioxidant activity which is considered important for anti-aging processes in animals. This study evaluated the anti-wrinkle effects of three different kinds of tea (Camellia sinensis) water extracts (CSWEs) including green, white, and black teas using a photoaged hairless mouse model. Data showed that the CSWE-treatment greatly improved skin conditions of mice suffering from UVB-induced photoaging, based on the parameters including the skin erythema index, moisture capacity, and transepidermal water loss. In addition, the wrinkle measurement and image analysis of skin replicas indicated that CSWEs remarkably inhibited wrinkle formation. In histological examination, the CSWE-treated mice exhibited diminished epidermal thickness and increased collagen and elastic fiber content, key signatures for skin restoration. Furthermore, the reduced expression of MMP-3, a collagen-degradative enzyme, was observed in the skin of CSWE-treated animals. Interestingly, comparative data between green, white, and black tea indicated that the anti-wrinkle activity of white tea and black tea is equally greater than that of green tea. Taken together, these data clearly demonstrated that CSWEs could be used as an effective anti-wrinkle agent in photoaged animal skin, implying their extended uses in therapeutics.
Protection of Saururus Chinensis Extract against Liver Oxidative Stress in Rats of Triton WR-1339-induced Hyperlipidemia
Kwon, Ryun Hee ; Ha, Bae Jin ;
Toxicological Research, volume 30, issue 4, 2014, Pages 291~296
DOI : 10.5487/TR.2014.30.4.291
Saururus chinensis has been reported to contain compounds such as lignans, alkaloids, diterpenes, flavonoids, tannins, steroids, and lipids. Fermentation is commonly used to break down certain undesirable compounds, to induce effective microbial conversion, and to improve the potential nutraceutical values. Previous studies have reported that the fermentation process could modify naturally occurring constituents, including isoflavons, saponins, phytosterols, and phenols, and could enhance biological activities, specifically antioxidant and antimicrobial properties. The probiotic strains used for fermentation exert beneficial effects and are safe. In this study, the antioxidative effects of the Bacillus subtilis fermentation of Saururus chinensis were investigated in a rat model with Triton WR-1339-induced hyperlipidemia by comparing the measured antioxidative biological parameters of fermented Saururus chinensis extract to those of nonfermented Saururus chinensis extract. Fermentation played a more excellent role than nonfermentation in ultimately protecting the body from oxidative stress in the liver of the experimental rats with Triton WR-1339-induced hyperlipidemia.
Peppermint Oil Promotes Hair Growth without Toxic Signs
Oh, Ji Young ; Park, Min Ah ; Kim, Young Chul ;
Toxicological Research, volume 30, issue 4, 2014, Pages 297~304
DOI : 10.5487/TR.2014.30.4.297
Peppermint (Mentha piperita) is a plant native to Europe and has been widely used as a carminative and gastric stimulant worldwide. This plant also has been used in cosmetic formulations as a fragrance component and skin conditioning agent. This study investigated the effect of peppermint oil on hair growth in C57BL/6 mice. The animals were randomized into 4 groups based on different topical applications: saline (SA), jojoba oil (JO), 3% minoxidil (MXD), and 3% peppermint oil (PEO). The hair growth effects of the 4-week topical applications were evaluated in terms of hair growth, histological analysis, enzymatic activity of alkaline phosphatase (ALP), and gene expression of insulin-like growth factor-1 (IGF-1), known bio-markers for the enhanced hair growth. Of the 4 experimental groups, PEO group showed the most prominent hair growth effects; a significant increase in dermal thickness, follicle number, and follicle depth. ALP activity and IGF-1 expression also significantly increased in PEO group. Body weight gain and food efficiency were not significantly different between groups. These results suggest that PEO induces a rapid anagen stage and could be used for a practical agent for hair growth without change of body weight gain and food efficiency.
Variation of Nephrotoxicity Biomarkers by Urinary Storage Condition in Rats
Lee, Jung-Min ; Han, Young-Hwan ; Choi, Su-Jeong ; Park, Ju-Seong ; Jang, Jeong-Jun ; Bae, Re-Ji-Na ; Lee, Mi Ju ; Kim, Myoung Jun ; Lee, Yong-Hoon ; Kim, Duyeol ; Lee, Hye-Young ; Park, Sun-Hee ; Park, Cheol-Beom ; Kang, Jin Seok ; Kang, Jong-Koo ;
Toxicological Research, volume 30, issue 4, 2014, Pages 305~309
DOI : 10.5487/TR.2014.30.4.305
Recently, there has been an increase in the use of several nephrotoxicity biomarkers in preclinical experiments. In addition, it has been indicated that the result may have been influenced by secondary factors, such as sample storage condition or storage period. In this study, we have assessed the variation in urinary nephrotoxicity biomarkers as a result of urine storage conditions and storage period of the urine. Urine was sampled from specific pathogen-free Sprague-Dawley rats (19 weeks old), which were housed individually in hanged stainless steel wire mesh cages. Urine was stored at
, or at
after sampling. The levels of the biomarkers such as beta-2 microglobulin (B2M), cystatin-C (Cys-C), N-acetyl-
-D-glucosaminidase (NAG), micro albumin (MA), micro protein (MP) were measured at 6, 24, 48 and 144 hr after sampling. The B2M level was significantly decreased at 6, 24, 48, and 144 hr compared to 0 hr at
(p < 0.05, p < 0.01, p < 0.05, and p < 0.05, respectively) and 24 and 144 hr at
(p < 0.01, p < 0.01, respectively). The Cys-C level was significantly decreased at 144 hr compared to 0 hr at
(p < 0.01), at
(p < 0.05) and at
(p < 0.01). MP and MA levels were not different for 144 hr in all storage conditions. Taken together, B2M and Cys-C levels were modulated by storage temperature and period. For the enhancement of test accuracy, it is suggested that strict protocols be established for samples to minimize the effects of the storage conditions on the detected levels of biomarkers.
Real-time Detection of Trace Copper in Brain and Kidney of Fish for Medical Diagnosis
Yang, Young Kyun ; Pack, Eun Chul ; Lee, Seung Ha ; Yoo, Hai-Soo ; Choi, Dal Woong ; Ly, Suw Young ;
Toxicological Research, volume 30, issue 4, 2014, Pages 311~316
DOI : 10.5487/TR.2014.30.4.311
For the detection of trace copper to be used in medical diagnosis, a sensitive handmade carbon nanotube paste electrode (PE) was developed using voltammetry. Analytical optimized conditions were found at 0.05 V anodic peak current. In the same conditions, various common electrodes were compared using stripping voltammetry, and the PE was found to be more sharply sensitive than other common electrodes. At optimum conditions, the working ranges of
were obtained. The relative standard deviation of
was determined to be 0.117% (n = 15), and the detection limit (S/N) was found to be
). The results were applied in detecting copper traces in the kidney and the brain cells of fish.