• Title/Summary/Keyword: cell toxicity

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Effect of acidic solutions on the microhardness of dentin and set OrthoMTA and their cytotoxicity on murine macrophage

  • Oh, Soram;Perinpanayagam, Hiran;Lee, Yoon;Kum, Jae-Won;Yoo, Yeon-Jee;Lim, Sang-Min;Chang, Seok Woo;Shon, Won-Jun;Lee, Woocheol;Baek, Seung-Ho;Kum, Kee-Yeon
    • Restorative Dentistry and Endodontics
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    • v.41 no.1
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    • pp.12-21
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    • 2016
  • Objectives: To evaluate the effects of three acids on the microhardness of set mineral trioxide aggregate (MTA) and root dentin, and cytotoxicity on murine macrophage. Materials and Methods: OrthoMTA (BioMTA) was mixed and packed into the human root dentin blocks of 1.5 mm diameter and 5 mm height. Four groups, each of ten roots, were exposed to 10% citric acid (CA), 5% glycolic acid (GA), 17% ethylenediaminetetraacetic acid (EDTA), and saline for five minutes after setting of the OrthoMTA. Vickers surface microhardness of set MTA and dentin was measured before and after exposure to solutions, and compared between groups using one-way ANOVA with Tukey test. The microhardness value of each group was analyzed using student t test. Acid-treated OrthoMTA and dentin was examined by scanning electron microscope (SEM). Cell viability of tested solutions was assessed using WST-8 assay and murine macrophage. Results: Three test solutions reduced microhardness of dentin. 17% EDTA demonstrated severe dentinal erosion, significantly reduced the dentinal microhardness compared to 10% CA (p = 0.034) or 5% GA (p = 0.006). 10% CA or 5% GA significantly reduced the surface microhardness of set MTA compared to 17% EDTA and saline (p < 0.001). Acid-treated OrthoMTA demonstrated microporous structure with destruction of globular crystal. EDTA exhibited significantly more cellular toxicity than the other acidic solutions at diluted concentrations (0.2, 0.5, 1.0%). Conclusions: Tested acidic solutions reduced microhardness of root dentin. Five minute's application of 10% CA and 5% GA significantly reduced the microhardness of set OrthoMTA with lower cellular cytotoxicity compared to 17% EDTA.

Effects of Squalene on SOD Activity and Histological Changes in Liver Toxicity Induced by Cadmium (Cadmium으로 유발된 간독성에서 SOD활성과 조직학적 변화에 대한 스쿠알렌의 효과)

  • Choi, Young-Bok;Kim, Jong-Se;Kim, Jung-Sam;Cho, Kwang-Pil;Hwang, Koo-Yeon;Park, Jung-Pyung
    • Applied Microscopy
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    • v.32 no.3
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    • pp.231-246
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    • 2002
  • This study was carried out to investigate the effect of squalene (SQ) on the mouse hepatotoxicity induced by cadmium. ICR male mouse weighting about 30 gm were injected $CdCl_2$ (5.0 mg/kg) and SQ (180 mg/kg) into intraperitoneal. At the 1, 2, 3, 4, 5, 6, 7 days, livers were treated with superoxide dismutase (SOD) activity and transmission electron microscopical method and then observed with electron microscope. The results obtained were summarized as follows: SOD activity in the liver, Group A was higher than in normal. Group B was lower than in Group A. In the histological observation, nucleus of Group A showed irregular shape. Inner cavity of mitochondria swellen and development of cristae weakened. Swelling of Lamellae of rough endoplasmic reticulum (RER) showed. Nucleus of group B showed normal shape. Typical lamellae of RER were observed. These results described above treatment of SQ decreased the hepatotoxicity of the $CdCl_2$ and SOD activity in the mouse liver, and then it suggests SQ may be effective for the recovery of hepatic cell.

Modulation of Chemical Stability and Cytotoxic Effects of Epigallocatechin-3-gallate by Different Types of Antioxidants (Epigallocatechin-3-gallate의 화학안정성 및 세포독성에 미치는 각종 항산화제의 영향)

  • Kim, Mi-Ri;Kang, Smee;Hong, Jung-Il
    • Korean Journal of Food Science and Technology
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    • v.43 no.4
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    • pp.483-489
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    • 2011
  • Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound frequently found in green tea, and its physiological actions have been extensively investigated. In the present study, changes in chemical stability and cytotoxic properties of EGCG in the presence of different types of antioxidants were investigated. The antioxidants used modulated the chemical stability of EGCG. Superoxide dismutase (SOD) significantly increased EGCG stability; EGCG was less stable in the presence of catalase. Ascorbic acid, N-acetylcysteine (NAC), and glutathione (GSH) stabilized EGCG concentration dependently. The $H_2O_2$ level generated from EGCG was decreased by catalase, SOD, and NAC but not by GSH. The cytotoxic effects of EGCG also decreased in the presence of NAC, catalase, and SOD. GSH, however, showed a complicated modulatory pattern according to the EGCG and GSH concentrations, and ascorbic acid rather enhanced EGCG toxicity. The results suggest that certain antioxidants could modulate the cytotoxic properties of EGCG in a cell culture system not only by removing reactive oxygen species but by modulating chemical stability and other factors, which should be considered carefully when studying reactive oxygen species-dependent mechanisms of EGCG.

Anti-oxidation and Anti-atopic Dermatitis Effect of Herbal Wood Vinegar (한방목초액의 항산화 및 항 아토피 효과)

  • Kim, Tagon;Nho, Hwa Jung;Jun, Sang Hui;Kim, Kang Bae;Kim, Donguk
    • Korean Chemical Engineering Research
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    • v.48 no.6
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    • pp.690-694
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    • 2010
  • In this study, herbal wood vinegar including Bambusoideae, Cinnamomi Cortex, Zingiberis Rhizoma was tested to see possibility for cosmetic or skin related medicine. Anti-oxidation effect of herbal wood vinegar was tested by DPPH free radical scavenging activity, and showed 97% inhibition rate at $50{\mu}g/ml$. Anti-bacterial effect was tested by disc diffusion method, and it indicated strong anti-bacterial activity against normal skin flora Staphylococcus aureus. Whitening effect was measured by tyrosinase inhibition assay, and it was lower compared with vitamin C. Stability test was done by MTT assay, and cell toxicity was relatively high. Stability was also checked, and there was not significant change in color, aroma, appearance and pH during storage. Anti-atopic dermatitis test was done by hairless mouse and herbal wood vinegar recovered damaged skin to almost normal condition after 9 days of application. IgE concentration in herbal wood vinegar treated mouse was also reduced 30% compared with control. From the study, herbal wood vinegar showed good anti-oxidation, anti-bacterial and anti-atopic dermatitis effect, and had promising application in cosmetic or skin related medicine.

Evaluation of Phototoxicity for Cosmetics and Alternative Method (화장품 광독성 평가와 동물대체시험법)

  • Lee, Jong-Kwon;Sin, Ji-Soon;Kim, Jin-Ho;Eom, Jun-Ho;Kim, Hyung-Soo;Park, Kui-Lea
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.31 no.3 s.52
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    • pp.245-251
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    • 2005
  • Safety is one of the key issue in the regulation of cosmetics. Cosmetic Act deals with it in Korea. The guidance for the testing cosmetic ingredients and their safety evaluation are prepared by Korea Food and Drug Administration. Ultraviolet radiation could Induce skin damage, edema, erythema, photoaging, immune dysfunction and skin cancer. Ultraviolet radiation is classified as Group 2A(probably carcinogenic to humans) by International Agenry for Reaserch on Cancer(IARC). The in vitro methodologies for evaluating the toxic potential of ingredients reported in the literature have not yet been sufficiently validated for use in areas other than the study for mutagenicity/genotoxicity, for pre-screening for severe irritancy, for screening of phototoxicity and for evaluating the percutaneous absorption. The 3T3 neutral red uptake photoxicity test (3T3 NRU PT) was accepted as OECD toxicity guideline in 2002. The 3T3 NRU PT is an in vitro method based on a comparison of the cytotoxicitv of a chemical when tested in the presence and in the absence of exposure to a non-cytotoxic dose of UVA/visible light.

Inhibitory Effect of Triticum aestivum Ethanol Extract on Lipid Accumulation in 3T3-L1 Preadipocytes (3T3-L1 세포에서 소맥엽 에탄올추출물의 지질생성 억제효과)

  • Lee, Sun-Hee;Xin, Mingjie;Luyen, Bui Thi Thuy;Cha, Ji-Yun;Im, Ji-Young;Kwon, Se-Uk;Lim, Sung-Won;Suh, Joo-Won;Kim, Young-Ho;Kim, Dae-Ki;Lee, Young-Mi
    • YAKHAK HOEJI
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    • v.55 no.6
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    • pp.478-484
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    • 2011
  • Non-alcoholic fatty liver disease is known to be frequently associated with obesity and type 2 diabetes. We examined the effects of EtOH extracts from Triticum aestivum on lipid accumulation during the differentiation of 3T3-L1 preadipocytes to screening the candidate materials in preventing non-alcoholic fatty liver disease. The lipid level in adipocytes was determined by Oil Red O staining. The treatment of 50% ethanol, but not water and 100% ethanol extracts, from Triticum aestivum at concentration of 0.5 $mg/ml$ inhibited lipid accumulation in 3T3-L1 cells, revealing no cell toxicity. Thus, the fractions of $CH_2Cl_2$, EtOAc and BuOH were separated from 50% EtOH extract to characterize anti-adipogenic effect. The $CH_2Cl_2$ fraction at concentration of $50{\mu}g/ml$ effectively inhibited the lipid accumulation in the adipocytes compared to those of EtOAc and BuOH at concentration of $50{\mu}g/ml$. The intracellular triglyceride accumulation also was significantly reduced by treatment of $CH_2Cl_2$ fraction in concentration-dependent manner. Western blot analysis showed that the $CH_2Cl_2$ fraction attenuated the intracelluar level of fatty acid synthase(FAS) accompanied by attenuated expression of Peroxidase proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) adipogenic transcription factor. These results suggest that $CH_2Cl_2$ fraction from 50% EtOH extract of Triticum aestivum may has the potent anti-adipogenic effects by inhibiting the transactivation of $PPAR{\gamma}$.

Toxicity and Characteristics of Antifungal Substances Produced by Bacillus amyloliquefaciens IUB158-03 (Bacillus amyloliquefaciens IUB158-03이 생산하는 항진균물질의 생화학적 특성 및 독성)

  • Kim, Hye-Young;Lee, Tae-Soo
    • Journal of Life Science
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    • v.19 no.11
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    • pp.1672-1678
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    • 2009
  • The purified antifungal substances produced by Bacillus amyloliquefaciens IUB158-03 was positive to ninhydrin but negative to aniline, suggesting that the antifungal substance could be a peptide. FAB-MS, UV adsorption spectrum, and amino acid composition analysis revealed that the molecular weight of the antifungal substance was 1042 and that maximal adsorption was at 220 nm and 277 nm. The antifungal substance was composed of $Asn_3$, $Gln_2$, $Ser_1$, $Gly_1$, and $Tyr_1$. The composition and structural characteristics of antifungal substance were analysed by $^1H$-NMR spectrum, $^1H$-COSY, HMQC, which revealed that the compound belongs to the iturin A family. Temperature and pH had little effect on the stability of the antifungal substance in the ranges of $-70{\sim}121^{\circ}C$ and pH 6.0~10.0, respectively. It showed strong antibiotic activity against fungi. An in vitro cytotoxicity test using NIH3T3 cell showed that the antifungal substance does not have cytotoxicity. The number of circulating leukocytes and the hematobiological analysis of the mice administered with the antifungal substances was similar to those of the control group, indicating no cytotoxicity in vivo. Therefore, the antifungal substances extracted from culture broth of Bacillus amyloliquefaciens IUB158-03 have future potential as biocontrol agents against plant diseases caused by fungi.

Effect of Piryongbanggamgil-tang on Airway Mucin Secretion, Production, Gene Expression and Hypersecretion of Mucus (필용방감길탕이 기도 뮤신의 분비, 생성, 유전자 발현 및 점액 과다 분비에 미치는 영향)

  • Kim, Yoon Young;Min, Sang Yeon;Kim, Jang Hyun
    • The Journal of Pediatrics of Korean Medicine
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    • v.28 no.2
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    • pp.56-71
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    • 2014
  • Objectives In this study, the author tried to investigate whether piryongbang-gamgil-tang (PGGT) significantly affect in vitro airway mucin secretion, PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production / gene expression from human airway epithelial cells and increase in airway epithelial mucosubstances and hyperplasia of tracheal goblet cells of rats. Materials and Methods For in vitro experiment, confluent RTSE cells were chased for 30 min in the presence of PGGT to assess the effect of PGGT on mucin secretion by enzyme-linked immunosorbent assay (ELISA). Also, effect of PGGT on PMA- or EGFor TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of PGGT and treated with PMA (10 ng/ml) or EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24 hrs, to assess both effect of PGGT on PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production by ELISA and gene expression by reverse transcription-polymerase chain reaction (RT-PCR). For in vivo experiment, the author induced hypersecretion of airway mucus and goblet cell hyperplasia by exposure of rats to $SO_2$ during 3 weeks. Effect of orally-administered PGGT during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats and hyperplasia of goblet cells were assesed by using histopathological analysis after staining the epithelial tissue with alcian blue. Possible cytotoxicities of PGGT in vitro were assessed by examining LDH release from RTSE cells and the rate of survival and proliferation of NCI-H292 cells. In vivo liver and kidney toxicities of PGGT were evaluated by measuring serum GOT/GPT activities and serum BUN/creatinine concentrations of rats after administering PGGT orally. Results (1) PGGT did not affect in vitro mucin secretion from cultured RTSE cells. (2) PGGT significantly inhibited PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions and the expression levels of MUC5AC mRNA from NCI-H292 cells. (3) PGGT decreased the amount of intraepithelial mucosubstances and showed the tendency of expectorating airway mucus already produced. (4) PGGT increased LDH release from RTSE cells. However, PGGT did not show in vivo liver and kidney toxicities and cytotoxicity to NCI-H292 cells. Conclusion The result from this study suggests that PGGT can regulate the production and gene expression of airway mucin observed in diverse respiratory diseases accompanied by mucus hypersecretion and do not show in vivo toxicity to liver and kidney functions after oral administration. Effect of PGGT with their components should be further studied using animal experimental models that reflect the diverse pathophysiology of respiratory diseases through future investigations.

pH-dependence in the inhibitory effects of Zn2+ and Ni2+ on tolaasin-induced hemolytic activity (Zn2+와 Ni2+에 의한 톨라신 용혈활성 저해효과의 pH 의존성)

  • Yun, Yeong-Bae;Choi, Tae-Keun;Kim, Young-Kee
    • Journal of Applied Biological Chemistry
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    • v.61 no.3
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    • pp.213-217
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    • 2018
  • Tolaasin secreted by Pseudomonas tolaasii is a peptide toxin and causes brown blotch disease on the cultivated mushrooms by collapsing cellular and fruiting body structure. Toxicity of tolaasin was evaluated by measuring hemolytic activity because tolaasin molecules form membrane pores on the red blood cells and destroy cell membrane structure. In the previous studies, we found that tolaasin cytotoxicity was suppressed by $Zn^{2+}$ and $Ni^{2+}$. $Ni^{2+}$ inhibited the tolaasin-induced hemolysis in a dose-dependent manner and its $K_i$ value was 1.8 mM. The hemolytic activity was completely inhibited at the concentration higher than 10 mM. The inhibitory effect of $Zn^{2+}$ on tolaasin-induced hemolysis was increased in alkaline pH, while that of $Ni^{2+}$was not much dependent on pH. When the pH of buffer solution was increased from pH 7 to pH 9, the time for 50% hemolysis ($T_{50}$) was increased greatly by $100{\mu}M$ $Zn^{2+}$; however, it was slightly increased by 1 mM $Ni^{2+}$ at all pH values. When the synergistic effect of $Zn^{2+}$ and $Ni^{2+}$ on tolaasin-induced hemolysis was measured, it was not dependent on the pH of buffer solution. Molecular elucidation of the difference in pH-dependence of these two metal ions may contribute to understand the mechanism of tolaasin pore formation and cytotoxicity.

In vivo Pharmacokinetics, Activation of MAPK Signaling and Induction of Phase II/III Drug Metabolizing Enzymes/Transporters by Cancer Chemopreventive Compound BHA in the Mice

  • Hu, Rong;Shen, Guoxiang;Yerramilli, Usha Rao;Lin, Wen;Xu, Changjiang;Nair, Sujit;Kong, Ah-Ng Tony
    • Archives of Pharmacal Research
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    • v.29 no.10
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    • pp.911-920
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    • 2006
  • Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.