• Journal of Life Science
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• v.23 no.11
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• pp.1388-1396
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• 2013

This study used an S-180 cell-injected mouse model to evaluate the antitumor effects of the acute and subacute toxicity of Keumsa (Phellinus linteus) extract intravenously administrated in ICR mice. When administered intravenously (31.3-250 mg/kg body weight), Keumsa (Phellinus linteus) extract significantly inhibited the growth of the solid tumor cell. The antitumor activity of Keumsa (Phellinus linteus) extract increased in a dose-dependent manner. The highest dose (250 mg/kg body weight) was highly effective, reducing tumor formation by 42.7% compared with the control group. In the acute toxicity test, $LD_{50}$ of the Keumsa (Phellinus linteus) extract showed 632.84 mg/kg (♂) and 814.48 mg/kg (♀) after intravenous administration. In addition, liver and spleen weight were increased in a dose-dependent manner. In the subacute toxicity test, the mice were intravenously administered over the course of 28 days. The $LD_{50}$ of the Keumsa (Phellinus linteus) extract showed 355.41 mg/kg (♂) and 383.53 mg/kg (♀) after intravenous administration. The liver and spleen weight also increased in a dose-dependent manner. In the case of the group that received more than 125 mg/kg of intravenous administration, exercise capacity, such as jumping ability and agility, were significantly increased. These results suggest that Keumsa (Phellinus linteus) extract can be regarded as a potent enhancer of the innate immune response, and it can be considered as a new natural product with low toxicity that may be used as a candidate for antitumor action.

• Bulletin of the Korean Chemical Society
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• v.32 no.6
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• pp.2021-2026
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• 2011

AgNPs (silver nanoparticles) has been widely used for the commercial products, which have antimicrobial agent, medical devices, food industry and cosmetics. Despite, AgNPs have been reported as toxic to the mammalian cell, lung, liver, brain and other organs and many researchers have investigated the toxicity of AgNPs. In this study, we investigated toxicity of the AgNPs to the liver cell using metabolomics based on HRMAS NMR (High Resolution Magic Angle Spinning Nuclear Magnetic Resonance) technics, which could apply to the intact tissues or cells, to avoid the sample destruction. Target profiling and multivariative statistical analysis were performed to analyze the 1D $^1H$ spectrum. The results show that the concentrations of many metabolites were affected by the AgNPs in the liver cell. The concentrations of glutathione (GSH), lactate, taurine, and glycine were decreased and most of amino acids, choline analogues, and pyruvate were increased by the AgNPs. Moreover, the levels of the metabolites were recovered upto similar level of metabolites in the normal cell by the pre-treatment of NAC, external antioxidant. The results suggest that the depletion of the GSH by the AgNPs might induce the conversion of lactate and taurine to the pyruvate.

• Korean Journal of Medicinal Crop Science
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• v.25 no.1
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• pp.45-51
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• 2017

Background: This study was performed to evaluate the protective effect of Saururus chinensis ethanol extract (SCE) against styrene toxicity in mouse spermatocyte cells [GC-2spd (ts) cell line]. Methods and Results: Cytotoxicity in mouse spermatocyte cells was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Generation of reactive oxygen species (ROS) was determined using 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) assay. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blotting were performed to quantify the mRNA and protein expression levels, resepectiviely, of stress or apoptosis-related genes including p21, p53, heat shock protein 70 (Hsp70), heat shock protein 90 (Hsp90), Bax, Bcl-2, and caspase-3. The results of the MTT assay showed that $50 {\mu}g/m{\ell}$ SCE did not affect cell viability. ROS generation in mouse spermatocyte cells increased by treatment with $100{\mu}M$ styrene, and decreased by co-treatment with SCE. SCE repressed the mRNA expression of stress-related genes, which increased by styrene treatment. In addition, SCE inhibited the apoptosis of mouse spermatocyte cells by ameliorating mRNA and protein levels of apoptotic genes that were altered by styrene treatment. Conclusions: These results suggest that SCE may alleviate styrene toxicity in mouse spermatocyte cells by reducing ROS stress and regulating genes related to styrene toxicity.

• Toxicological Research
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• v.30 no.3
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• pp.205-210
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• 2014

Didecyldimethylammonium chloride (DDAC) is used for various purposes, such as a fungicide for coolants, an antiseptic for wood, and disinfectant for cleaning. Despite the increasing likelihood of DDAC inhalation, available data on its toxicity from inhalation are scarce. Therefore, this study was aimed at confirming the toxicity of DDAC after inhalation exposure for 2 wk. Male Sprague-Dawley rats were exposed to approximately $0.15mg/m^3$, $0.6mg/m^3$, and $3.6mg/m^3$ DDAC aerosols in whole-body exposure chambers. After DDAC exposure for 2 wk, effects of DDAC on body weight, blood, bronchoalveolar lavage (BAL), and the lungs were verified. The mass median aerodynamic diameter of DDAC aerosols was $1.86{\mu}m$ and the geometric standard deviation was 2.75. The concentrations of DDAC aerosols for the low, medium, and high groups were $0.15{\pm}0.15mg/m^3$, $0.58{\pm}0.40mg/m^3$, and $3.63{\pm}1.56mg/m^3$, respectively. Body weight gain was significantly influenced by DDAC exposure. In the high group, a body weight decrease of 2.6 g was observed, whereas a 25.8 g increase was observed in the normal control group after the first 3 days. The low and medium groups showed 23.3 g and 20.4 g increases, respectively, after the first 3 days. Decreases in body weight were recovered during the next 4 days. In contrast, no changes were noted in hematological and blood biochemistry parameters after DDAC exposure. Furthermore, only mild effects were observed on bronchoalveolar cell differentiation counts and cell damage parameters in the BAL fluids of the medium and high groups. Although inflammatory cell infiltration and interstitial pneumonia were partially observed, fibrosis was not found in the lungs of the medium and high groups. In conclusion, body weight gain and the lungs were mainly affected by DDAC exposure. The no-observed-adverse-effect level (NOAEL) for DDAC was determined as $0.15mg/m^3$.

• Korean Journal of Environmental Biology
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• v.38 no.2
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• pp.271-277
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• 2020

Toxicities to many organs caused by humidifier disinfectants have been reported. Recently, humidifier disinfectants have been reported to cause cardiovascular, embryonic, and hepatic toxicities. This study was designed to investigate the toxic mechanism of humidifier disinfectants and compare toxicity in a cellular model and a zebrafish animal model. Because brain toxicity and skin toxicity have been less studied than other organs, we evaluated toxicity in a human dermal cell line and zebrafish under various concentrations of humidifier disinfectants that included polyhexamethyleneguanidine phosphate (PHMG), oligo-[2-(2-ethoxy)-ethoxyethyl-guanidinium-chloride] (PGH) and methylchloroisothiazolinone/methylisothiazolinone (CMIT/MIT). A human dermal fibroblast cell line was treated with disinfectants (0, 2, 4, 6, 8, and 16 mg L^-1) to compare their cytotoxicity. The fewest PHMG-treated cells survived (up to 33%), while 49% and 40% of the PGH- and CMIT/MIT-treated cells, respectively, survived. The quantification of oxidized species in the media revealed that the PHMG-treated cells had the highest MDA content of around 28 nM, while the PGH- and CMIT/MIT-treated cells had 13 and 21 nM MDA, respectively. As for brain toxicity, treatment of the zebrafish tank water with CMIT/MIT (final 40 mg L^-1) for 30 min resulted in a 17-fold higher production of reactive oxygen species (ROS) than in the control. Treatment with PGH or PHMG (final 40 mg L^-1) resulted in 15- and 11-fold higher production, respectively. The humidifier disinfectants (PHMG, PGH, and CMIT/MIT) showed severe dermal cell toxicity and brain toxicity. These toxicities may be relevant factors in understanding why some children have language disorders, motor delays, and developmental delays from exposure to humidifier disinfectants.

• The Korea Journal of Herbology
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• v.26 no.2
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• pp.31-37
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• 2011

Objectives : This study was focused to investigate the toxicity of Saussurea lappa (SL) extracts in HL-60 cells and human lymphocytes. We also examined the differentiation effect of SL against leukemia cells. Methods : For examining the toxicity of SL, cytokinesis-block micronucleus (CBMN) assay and single cell gel eletrophoresis (SCGE) assay were used in present study. The cell differentiation effect of SL was evaluated by nitroblue tetrazolium (NBT) reduction assay. Results : The inhibition of cell growth in HL-60 cells was observed in a dose-dependant manner after SL treatment for 24 h. According to SCGE assay, HL-60 cells treated with SL increased DNA damage at $10{\mu}g/m{\ell}$, while DNA damage was induced by 0.1, 1, $10{\mu}g/m{\ell}$ concentration of SL in human lymphocytes. Our results indicated that SL have no genotoxic effect in HL-60 cells and human lymphocytes. Additionally, the differentiation effect was induced in $1{\mu}g/m{\ell}$ SL-treated HL-60 cells. Conclusions : From above results it is suggested that SL could be beneficial for the preparation of the useful agent for treating leukemia.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.2
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• pp.65-71
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• 2008

The present study examined the inhibitory effect of licorice compounds glycyrrhizin and a metabolite $18{\beta}$-glycyrrhetinic acid on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse and on the 1-methyl-4-phenylpyridinium ($MPP^+$)-induced cell death in differentiated PC12 cells. MPTP treatment increased the activities of total superoxide dismutase, catalase and glutathione peroxidase and the levels of malondialdehyde and carbonyls in the brain compared to control mouse brain. Co-administration of glycyrrhizin (16.8 mg/kg) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. In vitro assay, licorice compounds attenuated the $MPP^+$-induced cell death and caspase-3 activation in PC12 cells. Glycyrrhizin up to $100{\mu}M$ significantly attenuated the toxicity of $MPP^+$. Meanwhile, $18{\beta}$-glycyrrhetinic acid showed a maximum inhibitory effect at $10{\mu}M$; beyond this concentration the inhibitory effect declined. Glycyrrhizin and $18{\beta}$-glycyrrhetinic acid attenuated the hydrogen peroxide- or nitrogen species-induced cell death. Results from this study indicate that glycyrrhizin may attenuate brain tissue damage in mice treated with MPTP through inhibitory effect on oxidative tissue damage. Glycyrrhizin and $18{\beta}$-glycyrrhetinic acid may reduce the $MPP^+$ toxicity in PC12 cells by suppressing caspase-3 activation. The effect seems to be ascribed to the antioxidant effect.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4107-4112
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• 2012

4-Nitroquinoline 1-oxide (4-NQO) a potent oral carcinogen, widely used for induction of oral carcinogenesis, has been found to induce lipid peroxidation in vivo and in vitro. Green tea contains a high content of polyphenols, which are potent antioxidants. Thus green tea polyphenols (GTP) might be expected play a protective role against 4-NQO induced lipid peroxidation and bone marrow toxicity. In the present study, a dose of 200 mg of GTP/kg b.wt/day was given orally for a week, simultaneously animals received 0.2 ml of 0.5% 4-NQO in propylene glycol (5 mg/ml) injected intramuscularly for three times/week. Oxidants and antioxidants such as malendialdehyde (MDA) and thiols, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) were significantly decreased in 4-NQO induced animals except MDA, and these parameters were brought back to near normalcy on treatment with GTP. The results suggest that GTP treatment offers significant protection against 4-NQO induced lipid peroxidation and bone marrow toxicity and might be a promising potential candidate for prevention of mutations leading to cancer.

• Analytical Science and Technology
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• v.34 no.6
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• pp.275-283
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• 2021

This study presents the development of cell-based microfluidic chips for the performance of acute eye irritation tests due to chemicals and examined some of their applications. Microfluidic chips were fabricated by photolithography and soft lithography, and they had three compartments with different areas for cell culture. Rabbit corneal epithelial cells were used for the eye irritation test. The death of cells cultured inside the chip was monitored at regular time intervals after treatment with an aqueous solution of chemicals, and the cell death rate constants were calculated based on the viability curve. The performance of the microfluidic chip was verified by examining the effects of cell-cell junctions, cell-substrate adhesion, and initial cell numbers compared to cell death rates. Eye irritation tests were performed at various concentrations of an aqueous solution of sodium dodecyl sulfate (SDS), a standard substance for the eye irritant test. The cells were exposed to the SDS aqueous solution for 300 s, and the resulting eye irritation was assessed by cell viability. Finally, the equation for calculating the toxicity score (TS) was derived based on the weighting factor for each compartment in the chip. The cell-based microfluidic chip developed in this study may be used for eye irritation tests from chemicals used in cosmetics and pharmaceuticals.

• YAKHAK HOEJI
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• v.43 no.4
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• pp.535-540
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• 1999

Glutamate (Glu) receptor-mediated excitoxicity has been implicated in many acute and chronic types of neurological disorders. Exposure of mature rat cortical neurons (15-18 days in culture) to the various concentrations of Glu resulted in a marked neuronal death, whereas immature rat cortical neurons (4∼5 days in culture) were resistant to the Glu-induced toxicity. Glu receptor subtype-specific agonists showed differential extent of toxicity in the immature neurons. The neurons treated with NMDA or kainate (KA) did not exhibit damage. However, quisqualate (QA) treatment induced a considerable cell death (36.1%) in immature enurons. The non-NMDA antagonist DNQX did not reduce this response. Interestingly, the QA-induced toxicity was potentiated by spermine in a concentration-dependent manner. Again, the spermine-enhanced damage was not altered by the polyamine antagonist ifenprodil. Taken together, unlike NMDA or KA, QA can induce neurotoxicity in immature rat cortical neurons and the QA-induced toxicity was potentiated by spermine. The lack of antagonizing effects of DNQX and ifenprodil on QA-induced toxicity and the potentiated toxicity by spermine, respectively, implies that both QA receptor and the polyamine site of NMDA receptor may not mediate the neurotoxicity observed in this study, and that a distinct mechanism(s) may be involved in excitotoxicity in immature neurons.