• Journal of Animal Reproduction and Biotechnology
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• v.37 no.4
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• pp.239-245
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• 2022

Protein and peptide candidates are screened to apply therapeutic application as a drug. Ensuring that these candidates are delivered and maximized effectiveness is still challenging and a variety of studies are ongoing. As drug delivery system vehicles, cell-penetrating peptide (CPP) can deliver various kinds of cargo into the cell cytosol. In a previous study, we developed Ara27 CPP, which are a zinc knuckle family protein of Arabidopsis, and confirmed internalization in human dermal fibroblasts and human dental pulp stem cells at low concentration with short time treatment condition without any toxicity. Ara27, an amphipathic CPP, could be modified and utilized in the biomedical field excluding the risk of toxicity. Therefore, we would like to confirm the non-toxic induced penetrating ability of Ara27 in various cell lines. The purpose of this study was to screen the cell internalization ability of Ara27 in various cell lines and to confirm Ara27 as a promising core CPP structure. First, Ara27 was screened to confirm non-toxicity concentration. Then, fluorescence-labeled Ara27 was treated on human normal cell lines, cancer cell lines and animal cell lines to identify the cellular internalization of Ara27. Ara27 was well intracellular localized in all cell lines and the intensity of fluorescence was remarkably increased in time pass manner. These results indicate that Ara27 has the potential as a core structure for applications in various drug delivery systems.

• Environmental Analysis Health and Toxicology
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• v.18 no.4
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• pp.295-303
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• 2003

Physiological cellular activities responses to cadmium (Cd) exposure in green algae with several reductases activities and viability of the cell were examined. The cell division of green algae, Selenastrum capricornutum treated with 5ppm was significantly decreased than that of normal algae. The mean cell number of normal algal culture was as twice much as than that of algae at 6 days after Cd treatment. The cellular viability of algae was analysed by flow-cytometry with fluorescent dye after esterase reaction on cell membrane. The 85.35% of cellular viability of normal culture was decreased to 34.35% when algae was treated with 5 ppm of Cd at 6 days after treatment. It was considered that those method of flow-cytometry is useful tool for toxicity test on micro-organisms in the respect of identifying cellular viability. Also, the activities of both glutathione peroxidase (GPX) and ascorbate peroxidase (APX), which are indirectly react against oxidative stress through reduction of glutathione by Cd were significantly increased with 25%. It is considered that both GPX and APX are involved in the metabolic pathway of Cd -detoxification with similar portion in Selenasturm capricornutum.

• Molecules and Cells
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• v.46 no.8
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• pp.496-512
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• 2023

A fructose-enriched diet is thought to contribute to hepatic injury in developing non-alcoholic steatohepatitis (NASH). However, the cellular mechanism of fructose-induced hepatic damage remains poorly understood. This study aimed to determine whether fructose induces cell death in primary hepatocytes, and if so, to establish the underlying cellular mechanisms. Our results revealed that treatment with high fructose concentrations for 48 h induced mitochondria-mediated apoptotic death in mouse primary hepatocytes (MPHs). Endoplasmic reticulum stress responses were involved in fructose-induced death as the levels of phosho-eIF2α, phospho-C-Jun-N-terminal kinase (JNK), and C/EBP homologous protein (CHOP) increased, and a chemical chaperone tauroursodeoxycholic acid (TUDCA) prevented cell death. The impaired oxidation metabolism of fatty acids was also possibly involved in the fructose-induced toxicity as treatment with an AMP-activated kinase (AMPK) activator and a PPAR-α agonist significantly protected against fructose-induced death, while carnitine palmitoyl transferase I inhibitor exacerbated the toxicity. However, uric acid-mediated toxicity was not involved in fructose-induced death as uric acid was not toxic to MPHs, and the inhibition of xanthine oxidase (a key enzyme in uric acid synthesis) did not affect cell death. On the other hand, treatment with inhibitors of the nicotinamide adenine dinucleotide (NAD)⁺-consuming enzyme CD38 or CD38 gene knockdown significantly protected against fructose-induced toxicity in MPHs, and fructose treatment increased CD38 levels. These data suggest that CD38 upregulation plays a role in hepatic injury in the fructose-enriched diet-mediated NASH. Thus, CD38 inhibition may be a promising therapeutic strategy to prevent fructose-enriched diet-mediated NASH.

• Molecular & Cellular Toxicology
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• v.4 no.4
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• pp.267-277
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• 2008

Benzene and ethylbenzene (BE), the volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Chronic exposure of benzene is responsible for myeloid leukemia and also ethylbenzene is also recognized as a possible carcinogen. To evaluate the BE effect on human, whole human genome 35 K oligonucleotide microarray were screened for the identification of the differential expression profiling. We identified 280 up-regulated and 201 down-regulated genes changed by more than 1.5 fold by BE exposure. Functional analysis was carried out by using DAVID bioinformatics software. Clustering of these differentially expressed genes were associated with immune response, cytokine-cytokine receptor interaction, toll-like signaling pathway, small cell lung cancer, immune response, apoptosis, p53 signaling pathway and MAPKKK cascade possibly constituting alternative or subordinate pathways of hematotoxicity and immune toxicity. Gene ontology analysis methods including biological process, cellular components, molecular function and KEGG pathway thus provide a fundamental basis of the molecular pathways through BEs exposure in human lymphoma cells. This may provides a valuable information to do further analysis to explore the mechanism of BE induced hematotoxicity.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.172-176
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• 2007

Butylated hydroxytoluene (BHT) is widely used antioxidant food additives. It has been extensively studied for potential toxicities. BHT appears adverse effects in liver and thyroid. In this study, we evaluated the genetic toxicity of BHT with more advanced methods, in vitro mouse lymphoma assay $tk^{+/-}$ gene assay (MLA) and in vivo mouse supravital micronucleus (MN) assay. BHT did not appear the significantly results in the absence and presence of metabolic activation system with MLA. Also, in vivo testing of BHT yielded negative results with supravital MN assay. These results suggest that BHT itself was not generally considered genotoxic.

• Molecular & Cellular Toxicology
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• v.1 no.1
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• pp.26-31
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• 2005

The detection and the regulation of man-made synthetic chemicals and the establishment of toxicity that may pose a genetic hazard in our environment are subjects of great concern because of its close correlation between environmental contamination and human health. Since the tens of thousands of man-made chemicals that have been introduced into the environment in the last few decades must also be tested for their damaging effect on DNA, the agents that cause this damage must be identified.

• Environmental Analysis Health and Toxicology
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• v.14 no.3
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• pp.75-79
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• 1999

Due to increasing marine pollution there is a great possibility that seaweed is contaminated with polycyclic aromatic hydrocarbons (PAHs). To investigate the effect of processing on PAM removal from Porphyra tenera (laver) contaminated PAH, laver was contaminated with fluoranthene known to have a strong photoinduced toxicity, followed by washings and drying, which are usual processes for dried laver preparation. Sample at each step was collected and its toxicity was evaluated using cultured animal cells as well as analyzing PAH contents. Fluoranthene level in laver was significantly lowered by sequential washings with sea water and distilled water, but not by drying. Fluoranthene content in raw laver right after contamination was 221 ppm and decreased to 130 ppm by washings with seawater plus distilled water while its level was not lurker lowered by drying process. Cytotoxicity and photoinduced cytotoxicity in mammalian cells were significantly elevated in laver extracts containing fluoranthene. Cellular arylhydrocarbon hydroxylase (AHH), one of the biomarkers for cellular accumulation of PAH, was greatly induced by laver extract contaminated with fluoranthene. These results suggest that photoinduced toxicity and AHH activity can be used to monitor contamination of seafood by PAHs. Fluoranthene accumulated in laver was efficiently removed by sequential washings with seawater and tap water for 24 hrs and 12 hrs, respectively.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.6
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• pp.413-420
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• 2002

Mercury is one of the most frequently used heavy metal in dental clinic. Mercury poisoning rises up when someone is exposed to mercury chronically. In 1818, Amalgam was used for dental restorative procedure, and after then study about mercury toxicity has begun. Clinical signs of mercury toxicity in oral & maxillofacial area were increases of salivation, metallic taste, swelling and pain of tongue, redness and ulceration of oral mucosa, and increased mobility and loss of teeth. After we injected mercury($HgCl_{2}$) into intraperitoneum of rat, studied about histopathological changes of submandibular gland cell. Experimental group was divided into two groups by amount of mercury. (Group 1 was 0.5mg/Kg of mercury injection, group 2 was 1.0mg/Kg of mercury injection.) 1. After 3days of intraperitoneal injection, black granules were observed at macrophage cell in both group. In group 2, author found hyperchromatism of nucleus, and vacuolization of cellular matrix and nucleus of acinar cell. 2. After 1week of intraperitoneal injection, author found severe vacuolization of nucleus and cellular matrix, and irregular granules around nuclear membrane at mucous cell and serous cell in both group. Vacuolization of nucleus and cellular matrix was seen at duct cell in group 2. 3. After 2weeks of intraperitoneal injection, author could found severe vacuolization of cellular matrix, and sometimes nucleus was positioned in central area of cellular matrix at mucous and serous cell in both group. Vacuolization of nucleus and cellular matrix was found at vascular endothelial cell in group 2. 4. After 4weeks of intraperitoneal injection, destruction and distortion of gland cells were distinct. Vacuolization and destruction of nucleus and cellular matrix was found at duct cell in group 2. After intraperitoneal injection of mercury, we found equanimity of mercury and destruction of cellular matrix at serous cell, mucous cell, and duct cell of submandibular gland. So, we thought that metallic taste of mercury poisoning patient would be due to excretion of saliva containing mercury.

• Toxicological Research
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• v.23 no.1
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• pp.1-9
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• 2007

Transporters are membrane proteins that mediate the transfer of substrate across the cellular membrane. In this overview, the characteristics and the toxicological relevance were discussed for various types of transporters. For drug transporters, the overview focused on ATP-binding cassette transporters and solute carrier family 21A/22A member transporters. Except for OCTN transporters and OATP transporters, drug transporters tend to have broad substrate specificity, suggesting drug-drug interaction at the level of transport processes (e.g., interaction between methotrexate and non-steroidal anti-inflammatory agents) is likely. For metal transporters, transporters for zinc, copper and multiple metals were discussed in this overview. These metal transporters have comparatively narrow substrate specificity, except for multiple metal transporters, suggesting that inter-substrate interaction at the level of transport is less likely. In contrast, the expressions of the transporters are often regulated by their substrates, suggesting cellular adaptation mechanism exists for these transporters. The drug-drug interactions in drug transporters and the cellular adaptation mechanisms for metal transporters are likely to lead to alterations in pharmacokinetics and cellular metal homeostasis, which may be linked to the development of toxicity. Therefore, the transporter-mediated alterations may have toxicological relevance.

• Molecular & Cellular Toxicology
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• v.4 no.1
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• pp.22-30
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• 2008

Malachite Green (MG), a toxic chemical used as a dye, topical antiseptic and antifungal agent for fish, is highly soluble in water, cytotoxic to various mammalian cells and also acts as a liver tumor promoter. In view of its industrial importance and possible exposure to human beings, MG possesses a potential environmental health hazard. So, we performed with HepG2, a human hepatocellular carcinoma cell line, to identify the differentially expressed genes (DEGs) related to toxicity of MG. And we compared gene expression between control and MG treatment to identify genes that are specifically or predominantly expressed by employing annealing control primer (ACP)-based $GeneFishing^{TM}$ method. The cytotoxicity $(IC_{20})$ of MG was determined above the $0.867{\mu}M$ in HepG2 cell for 48 h treatment. And the DEGs of MG were identified that 5 out of 6 DEGs were upregulated and 1 out of 6 DEGs was down-regulated by MG. Also, MG induced late apoptosis and necrosis in a dose dependent in flow cytometric analysis. Through further investigation, we will identify more meaningful and useful DEGs on MG, and then can get the information on mechanism and pathway associated with toxicity of MG.