• Journal of Digestive Cancer Research
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• v.11 no.1
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• pp.45-48
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• 2023

One of the most common side effects of chemotherapeutic agents is chemotherapy-induced peripheral neuropathy (CIPN). The occurrence of CIPN is increasing as the survival rate of patients with cancer improves and the cumulative dose or duration of neurotoxic drugs increases. Approximately 30-40% of patients receiving neurologically toxic drugs experience CIPN, which eventually increases the burden of medical expenses. However, preventive measures against CIPN have not yet been established. Clinical trials have tested various drugs for the management of neuropathic pain, but only duloxetine has shown any significant effect. Further studies should evaluate nonpharmaceutical treatments, such as exercise.

• Bulletin of the Korean Chemical Society
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• v.34 no.1
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• pp.201-206
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• 2013

The second-order rate constants have been measured spectrophotometrically for the reactions of paraoxon 1 and parathion 2 with a series of alicyclic secondary amines, $OH^-$ and $HOO^-$ ions in $H_2O$ at $25.0{\pm}0.1^{\circ}C$. A linear Br${\o}$nsted-type plot with ${\beta}_{nuc}$ = 0.40 was obtained for the reactions of 1 with amines and $OH^-$. The reaction has been concluded to proceed through a concerted mechanism. $HOO^-$ deviates positively from the linear Br${\o}$nsted-type plot, implying that the ${\alpha}$-effect is operative. The magnitude of the ${\alpha}$-effect ($k_{HOO^-}/k_{OH^-}$) was found to be ca. 55 for the reaction of 1 and 290 for that of parathion 2, indicating that $HOO^-$ is highly effective in decomposition of the toxic phosphorus compounds although it is over 4 $pK_a$ units less basic than $OH^-$. Among the theories suggested as origins of the ${\alpha}$-effect (e.g., TS stabilization through an intramolecular Hbonding interaction, solvent effect, and polarizability effect), polarizability effect appears to be the most important factor for the ${\alpha}$-effect in this study, since the polarizable $HOO^-$ exhibits a larger ${\alpha}$-effect for the reaction of the more polarizable substrate 2.

• Toxicological Research
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• v.12 no.2
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• pp.203-211
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• 1996

Methanol has been widely used as an industrial solvent and environmental exposure to methanol would be expected to be increasing. In humans, methanol causes metabolic acidosis and damage to ocular system, and can lead to death in severe and untreated case. Clinical symptoms are attributed to accumulation of forrnic acid which is a metabolic product of methanol. In humans and primates, formic acid is accumulated after methanol intake but not in rodents due to the rapid metabolism of methanol. Neverthless, the developmental and reproductive toxicity were reported in rodents. Previous reports showed that perinatal exposure to ethanol produces a variety of damage in human central nervous system by direct neurotoxicity. This suggests that the mechanism of toxic symptoms by methanol in rodents might mimic that of ethanol in human. In the present study I hypothesized that methanol can also induce toxicity in neuronal cells. For the study, primary culture of rat hippocampal neurons and glias were empolyed. Hippocampal cells were prepared from the embryonic day-17 fetuses and maintained up to 7 days. Effect of methanol (10, 100, 500 and 1000 mM) on neurite outgrowth and cell viability was investigated at 0, 18 and 24 hours following methanol treatment. To study the changes in proliferation of glial cells, protein content was measured at 7 days. Neuronal cell viability in culture was not altered during 0-24 hours after methanol treatment. 10 and 100 mM methanol treatment significantly enhanced neurite outgrowth between 18-24 hours. 7-day exposure to 10 or 100 mM methanol significantly increased protein contents but that to 1000 mM methanol decreased in culture. In conclusion, methanol may have a variety of effects on growing and differentiation of neurons and glial cells in hippocampus. Treatment with low concentration of methanol caused that neurite outgrowth was enhanced during 18-24 hours and the numbers of glial cell were increased for 7 days. High concentration of methanol brought about decreased protein contents. At present, the mechanism responsible for the methanol- induced enhancement of neurite outgrowth is not clear. Further studies are required to delineate the mechanism possibly by employing molecular biological techniques.

• Animal cells and systems
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• v.5 no.4
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• pp.327-331
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• 2001

There is a critical developmental period during which brain sexual differentiation proceeds irreversibly under the influence of gonadal hormone. Recently, kinesin superfamily-associated protein 3 (KAP3) gene expressed during the 'critical period' of rat brain differentiation was identified by us (Choi and Lee, 1999). KAP3 functions as a microtubule-based motor that transports membranous organelles anterogradely in cells, including neurons (Yamazaki et al., 1996). mRNA level of KAP3 gene markedly increased before the initiation of puberty. Neonatal treatment of estrogen clearly inhibited the prepubertal increase in KAP3 mRNA level (Choi and Lee, 1999). In the present study, we aimed to investigate the effects of polychlorinated biphenyls (PCBs), as endocrine disruptors (EDs) on the expression of KAP3 gene during the 'critical period' of rat brain development. In our data, PCBs significantly decreased the expression of KAP3 gene in the fetal (day 17) and the neonatal (day 6 after birth in) male and female rat brains. The body weight and the breeding ability were significantly decreased in the PCBs-exposed rats compared with the control. These results showed that PCBs affect the transcriptional level of brain sexual differentiation related gene, KAP3, in the fetal and the neonatal rat brains. The maternal exposure to the PCBs may lead to toxic response in embryonic brain sexual differentiation and breeding ability after sexual maturation. This study indicates that KAP3 gene may be useful as a gene marker to analyze the molecular mechanism of toxic response in the animal brain development and sexual maturation exposed to PCBs.

• Molecular & Cellular Toxicology
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• v.4 no.3
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• pp.260-266
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• 2008

Recently, there has been scientific discussion on the utility of -omics techniques such as genomics, proteomics, and metabolomics within toxicological research and mechanism-based risk assessment. Toxicogenomics is a novel approach integrating the expression analysis of genes (genomic) or proteins (proteomic) with traditional toxicological methods. Since 1999, the toxicogenomic approach has been extensively applied for regulatory purposes in order to understand the potential toxic mechanisms that result from chemical compound exposures. Therefore, this article's purpose was to consider the utility of toxicogenomic profiles for improved risk assessment, explore the current limitations in applying toxicogenomics to regulation, and finally, to rationalize possible avenues to resolve some of the major challenges. Based on many recent works, the significant impact toxicogenomic techniques would have on human health risk assessment is better identification of toxicity pathways or mode-of-actions (MOAs). In addition, the application of toxicogenomics in risk assessment and regulation has proven to be cost effective in terms of screening unknown toxicants prior to more extensive and costly experimental evaluation. However, to maximize the utility of these techniques in regulation, researchers and regulators must resolve many parallel challenges with regard to data collection, integration, and interpretation. Furthermore, standard guidance has to be prepared for researchers and assessors on the scientifically appropriate use of toxicogenomic profiles in risk assessment. The National Institute of Toxicological Research (NITR) looks forward to an ongoing role as leader in addressing the challenges associated with the scientifically sound use of toxicogenomics data in risk assessment.

• Molecular & Cellular Toxicology
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• v.4 no.3
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• pp.183-191
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• 2008

Volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. And VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Benzene is the most widely used prototypical VOC and the toxic mechanisms of them are still unclear. The multi-step process of toxic mechanism can be more fully understood by characterizing gene expression changes induced in cells by toxicants. In this study, DNA microarray was used to monitor the expression levels of genes in HepG2 cells and HL-60 cells exposed to the benzene on IC20 and IC50 dose respectively. In the clustering analysis of gene expression profiles, although clusters of HepG2 and HL-60 cells by benzene were divided differently, expression pattern of many genes observed similarly. We identified 916 up-regulated genes and 1,144 down-regulated genes in HepG2 cells and also 1,002 up-regulated genes and 919 down-regulated genes in HL-60 cells. The gene ontology analysis on genes expressed by benzene in HepG2 and HL-60 cells, respectively, was performed. Thus, we found some principal pathways, such as, focal adhesion, gap junction and signaling pathway in HepG2 cells and toll-like receptor signaling pathway, MAPK signaling pathway, p53 signaling pathway and neuroactive ligand-receptor interaction in HL-60 cells. And we also found 16 up-regulated and 14 down-regulated commonly expressed total 30 genes that belong in the same biological process like inflammatory response, cell cycle arrest, cell migration, transmission of nerve impulse and cell motility in two cell lines. In conclusion, we suggest that this study is meaningful because these genes regarded as strong potential biomarkers of benzene independent of cell type.

• Korean Journal of Microbiology
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• v.28 no.1
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• pp.76-82
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• 1990

In samples taken from mouth of the Nakdong River, mercury-resistant bacteria grown on the media supplemented with over 20 ppm of mercuric chlorice were below 0.3% of all aerobic heterotrophs. Among them, seven strains grown over 100 ppm of mercuric chloride were isolated and all were identified as Pseudomonas. The toxic effect of mercury on the growth of the most resistant strain N14 was influenced by the organic compounds and concentration. The growth and physiological activity to N14 strain were affected by toxic mercury in the early stage: The viable count and glucose turn over rate of N14 strain dropped to the lowest level as soon as the bacteria came into contact with mercury. During the extended lag period, however, bacteria accommodated to the stress and the viable count and glucose turnover rate increased. After the lag period, bacteria began to proliferate and their growth reached similar level to that of control. In crude extracts of N14 strain grown in nutrient browth containing. $10{\mu}M$ $HgCl_{2}$, a mercuric ion dependent oxidation of NADPH was demonstrated. Therefore the mechanism of mercury-resistance of the N14 strain involved the elimination of the mercury from growth media. In the N14 strain which a wide range of resistance to antibiotics was observed in, four multiple plasmids were detected. As a result, the supposition that N14 strain has a plasmid-encoded enzyme system may be quite within the realms of possobility.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.187-192
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• 2009

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens. The stimulation of TLRs by microbial components triggers the activation of the myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-$\beta$ (TRIF)-dependent downstream signaling pathways. TLR/MyD88 signaling pathway induces the activation of nuclear factor-kappa B (NF-${\kappa}B$) and the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-$1{\beta}$. On the other hand, TLR/TRIF signaling pathway induces the delayed-activation of NF-${\kappa}B$ and interferon regulatory factor 3 (IRF3), and the expression of type I interferons (IFNs) and IFN-inducible genes. The divalent heavy metal cadmium (Cd) is clearly toxic to most mammalian organ systems, especially the immune system. Yet, the underlying toxic mechanism(s) remain unclear. Cd inhibits the MyD88-dependent pathway by ceasing the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether Cd inhibits the TRIF-dependent pathway. Presently, Cd inhibited NF-${\kappa}B$ and IRF3 activation induced by lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid. Cd inhibited LPS-induced IRF3 phosphorylation and IFN-inducible genes such as interferon inducible protein-10 and regulated on activation normal T-cell expressed and secreted (RANTES). These results suggest that Cd can modulate TRIF-dependent signaling pathways of TLRs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.495-498
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• 2002

Cytotoxicity of glucose oxidase(GO) and neuroprotective effect of Aconiti Radix(AKR) against GO-induced neurotoxicity were measured for elucidating the mechanism of cardiotoxicity on cultured mouse myocardial cells by MTT assay after myocardial cells were cultured for 24 hours at various concentrations of GO. GO was toxic in a time-and dose-dependent manner on cultured myocardial cells after myocardial cells were grown for 24 hours in media containing 5～40mU/ml GO. While, cultures were pretreated with 50 μg/ml AKR for 2 hours increased remarkably cell viability. From the above results, it is suggested that GO is toxic on cultured mouse myocardial cells by the decrease of cell viability, and herb medicine such as AKR is very effective in the prevention of myocardial toxicity induced by GO.

• The Journal of Korean Medicine
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• v.20 no.1 s.37
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• pp.142-150
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• 1999

In order to elucidate toxic the mechanism of myocardial damage and the protective effect of herbal extract, Sophorae Radix(SR) against myocardiotoxicity, the cytotoxic effect of adriamycin and cardioprotective effect of SR were examined by MTT assay, LDH activity, heart beat rate and light microscopy after cultured myocardial cells derived from neonatal mouse were treated with various concentrations of adriamycin, an inducer of myocardiotoxicity. Adriamycin induced a decrease of cell viability, an increase in the amount of lactate dehydrogenase(LDH), and a decrease in the heart beat rate and a decrease in the number of cells, when administered to cultures myocardial cells in a dose-dependent manner. In cardioprotective effect of SR. SR showed the decrease of amount of LDH, and an increase of heart beating rate and cells in number on cultured myocardial cells damaged by adriamycin. From the above results, it is suggested that adriamycin shows toxic effect in cultured myocardial cells derived from a neonatal mouse, and herbal extract such as SR is very effective in the prevention of adriamycin-induced cardiotoxicity.