• Journal of the Korea Academia-Industrial cooperation Society
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• v.15 no.4
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• pp.2189-2198
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• 2014

Paraquat (PQ) is a very effective and widely used herbicide that was commercially introduced in 1962. In this study, instead of using antioxidants like in the past, to inhibit the formation of PQ-induced ROS, we attempted to reduce the oxygen concentration by using non-lethal hypoxia therapy. Therefore, we studied the toxicity of PQ in vivo, analyzed the major effects of ROS on the targeted lung tissue and compared the results with the gross histological changes after the cell protective effect of non-lethal hypoxia therapy. In vivo studies demonstrated that low-concentration oxygen therapy (i.e., 10-12% oxygen) in rats administered with PQ was associated with a higher survival rate than in rats that received only PQ. In vivo non-lethal hypoxia treatment showed better survival and less lung tissue damage. Using a hypoxic/anaerobic incubator with integrated multifaceted molecular analysis, including MDA assay, glutathione assay, and SOD assay, we established an optimal, significantly reduced in vivo non-lethal hypoxia treatment by exploiting the PQ-induced cytotoxicity responses.

• Korean Journal of Environmental Biology
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• v.34 no.2
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• pp.107-115
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• 2016

Currently, there are 442 operating nuclear power plants in the world, and 62 more are under construction. According to this reasoning, the treatment of radioactive waste is important to prevent the environmental ecosystem including humans, animals, and plants. Especially, a leakage of radioactive waste causes not only regional problem but also serious global one. In this study, we demonstrate the effect of radioisotopes (e.g., cesium, strontium, and cobalt) on a 3D culture cell. To develop the 3D cell culture system, we used a 96-well-culture plate with biocompatible agarose hydrogel. Using this method, we can perform the 3D cell culture system with three different cell lines such as HeLa, HepG2, and COS-7. In addition, we conducted a cell viability test in the presence of radioisotopes. Interestingly, the 3D morphological cells showed 42% higher cell viability than those on the 2D against cesium. This result indicates that the 3D platform provides cells morphological and physiological characteristic similar to in vivo grown tissues. Moreover, it overcomes the limitation of conventional cell culture system that can't reflect in vivo systems. Finally, we believe that the proposed approach can be applied a new strategy for simple high-throughput screening and accurate evaluation of metal toxicity assay.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.10
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• pp.1404-1410
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• 2011

Biological compounds (caffeic acid, rosemarinic acid, and chlorogenic acid) from mulberry leaf extracts were administered to mice in order to confirm their stability. All male and female mice survived upon a 4,000 mg/g dose in an acute toxicity test, and they also survived after injection of 2,000 mg/kg for 13 weeks repeatedly. Therefore, the level of toxicity was not high. In a comparison of the control and test groups, there were no significant differences upon naked eye inspection, and the weights of stomachs infected by Helicobacter pylori were not significantly different. Regarding the effects on immune cells, NO of macrophages decreased more than that of control when medicine was administered. The spleens of the female mice group proliferated slightly in LPS and Con A within 48 hr, whereas the other test group showed a similar level and the cell toxicity of natural killing cells decreased. Therefore, we concluded that caffeic acid, rosemarinic acid, and chlorogenic acid from mulberry leaf extracts are not harmful for the treatment of infected patients the development as a healthy functional food.

• The Korean Journal of Mycology
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• v.30 no.2
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• pp.119-123
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• 2002

In the previous studies, we surveyed 68 Korean wild mushrooms for their hemolytic activity and found that cold-water extract of Hebeloma crustuliniforme contained heat-resistant hemolysin. In this study, partially purified hemolysin of the mushroom was obtained by cold-water extraction followed by precipitation with ammonium sulfate, solubility fractionation and then dialysis. The hemolysin was found to be > 12,000 in molecular weight and its optimal hemolytic temperature was $37^{\circ}C$ and it's hemolytic activity, on washed erythrocytes and unwashed erythrocytes, respectively, was in the order of sheep > rat > human ${\geq}$ mouse > chicken and sheep > mouse > human ${\geq}$ rat > chicken. When ip injected into ICR mice at 1.38 mg/kg, it incurred prompt hemolysis as well as severe renal toxicity and hepatotoxicity. These results strongly suggest that the toxicity of Hebeloma crustuliniforme, which had been well-known as a toxic wild mushroom, may be at least partly due to its hemolysin.

• Environmental Mutagens and Carcinogens
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• v.16 no.1
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• pp.6-12
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• 1996

To investigate the clastogenicity of taxol and its precursor, 10-aleacetyl baccatin III, we performed chromosomal aberration assay with chinese hamster lung cells in vitro. The IC$_{50}$ values of taxol and 10-deacetyl baccatin III were determined as $1/16 \times 10^{-4}$ M (5.34 $\mu$g/ml) and $1 \times 10^{-2}$ M (560 $\mu$g/ml) in MTT assay, respectively. It means that the cytotoxicity of taxol revealed 100 times more cytotoxic than 10-deacetyl baccatin III in chinese hamster lung cell line. Nevertheless the strong positive genetic toxicity of taxol in the bone marrow micronucleus assay in vivo which was recently reported, we observed weak positive clastogenicity of taxoi only in the absence of metabolic activation system in the concentration ranges used in this experiment. Moreover, to clarify the involvement of metabolic fate of taxol because of its strong positive result in vivo, 10-deacetyl baccatin III which is a precursor in taxol synthesis, also subjected in chromosomal aberration assay in vitro. However, we observed no clastogenicity of 10-deacetyl baccatin III in this experiment. From above results, it was suggested that the esterification at C-13 appears to be relative for its genetic toxicity in chromosome aberration using chinese hamster lung cell in vitro.

• YAKHAK HOEJI
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• v.44 no.5
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• pp.478-487
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• 2000

This study was carried out to find new anti-tumor agent producing microbe and to characterize the anti-tumor agent produced from the microbe. Purified compound that has a high cytotoxicity against tumor cell-lines could be obtained from the broth culture filtrates of Streptomyces sp.409 strain isolated from soil in Korea. The in vitro cytotoxicity the in vivo evaluation of acute toxicity the safety assessment of the anti-tumor compounds and the taxonomic characteristics of the anti-tumor agent were measured. The antitumor compound 1 and 2 were obtained from the broth culture filtrates of Streptomyces sp.409 strain. The cytotoxicity of the compound 1 against tumor cell-line P388D$_1$ showed almost 4.5 times higher than that of adriamycin. However in the cytotoxicity against normal cell line Vero E6, adriamycin showed adversely 4 times higher than the compound 1 ($IC_{50}$/ value: 228.7 $\mu\textrm{g}$/$m\ell$). In comparison study with compound 1 and compound 2 in the in vitro cytotoxin productivity against tumor cell lines, $IC_{50}$/ value of the compound 1 was 0.25 $\mu\textrm{g}$/$m\ell$ in tumor cell line P388D$_1$and 0.53 $\mu\textrm{g}$/$m\ell$ in tumor cell-line L1210, and that of the compound 2 was 7.18 $\mu\textrm{g}$/$m\ell$ and 35.71 $\mu\textrm{g}$/$m\ell$, respectively; LD$_{50}$ value of the compound 1 in the in vivo acute toxicity in mice was 22.62 $\mu\textrm{g}$/kg body weight. These results suggest that compound 1 purified from Streptomyces sp. 409 has anti-tumor activity and will be developed as an anti-tumor drug.g.

• Parasites, Hosts and Diseases
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• v.54 no.2
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• pp.155-161
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• 2016

Toxoplasma gondii is an important opportunistic pathogen that causes toxoplasmosis, which has very few therapeutic treatment options. The most effective therapy is a combination of pyrimethamine and sulfadiazine; however, their utility is limited because of drug toxicity and serious side effects. For these reasons, new drugs with lower toxicity are urgently needed. In this study, the compound, (Z)-1-[(5-nitrofuran-2-yl)methyleneamino]-imidazolidine-2,4-dione (nitrofurantoin), showed anti-T. gondii effects in vitro and in vivo. In HeLa cells, the selectivity of nitrofurantoin was 2.3, which was greater than that of pyrimethamine (0.9). In T. gondii-infected female ICR mice, the inhibition rate of T. gondii growth in the peritoneal cavity was 44.7% compared to the negative control group after 4-day treatment with 100 mg/kg of nitrofurantoin. In addition, hematology indicators showed that T. gondii infection-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, biochemical parameters involved in liver injury, were reduced by nitrofurantoin significantly. Moreover, nitrofurantoin exerted significant effects on the index of antioxidant status, i.e., malondialdehyde (MDA) and glutathione (GSH). The nitrofurantoin-treated group inhibited the T. gondii-induced MDA levels while alleviating the decrease in GSH levels. Thus, nitrofurantoin is a potential anti-T. gondii candidate for clinical application.

• Journal of Pharmaceutical Investigation
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• v.17 no.4
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• pp.197-204
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• 1987

Novel pranoprofen algininate and lysinate salts were manufactured and their salt formation was confirmed by melting point, infrared spectroscopy, nuclear magnetic resornance spectroscopy, differential scanning calorimetry and powder X-ray diffractometry. The physical properties of pranoprofen lysinate and argininate salts were compared with those of pranoprofen through in vitro and in vivo tests. Solubility, $pK_a$ and lipid-water partition coefficient were measured through in vitro experiments, while antiinflammatory efficacy, analgesic effect, acute toxicity and in situ absorption were tested through in vivo experiments. The results obtained were as follows: 1) The solubilities of pranoprofen argininate and lysinate salts were increased markedly in pH 6.8 and pH 7.5 phosphate buffer solutions, comparing with that of pranoprofen itself. 2) $pK_a$ values of pranoprofen, pranoprofen argininate and lysinate salts were 6.34, 7.99 and 7.56 in carbon tetrachloride, and 5.86, 6.69 and 7.92 in chloroform, respectively by liquid-liquid partition method. 3) The lipid-water partition coefficients of pranoprofen argininate and lysinate salts were increased more than that of pranoprofen in carbon tetrachloride, chloroform, or benzene-pH 6.8 buffer system, but were nearly identical using pH 1.2 buffer as water phase. 4) Antiinflammatory effects of pranoprofen argininate and lysinate salts were remarkably increased and analgesic effects of the salts were as same as that of pranoprofen. 5) Pranoprofen argininate and lysinate salts were safer than pranoprofen itself in acute toxicity, and the in situ absorption rates of pranoprofen, pranoprofen argininate and lysinate salts were 0.392, 0.960 and $0.762\;hr^{-1}$, respectively according to the rat intestine recirculation experiment.

• The Korea Journal of Herbology
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• v.31 no.4
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• pp.1-10
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• 2016

Objectives: In Korean medicine, Curculiginis Rhizoma was treated for arthritis in remedy. But efficacy of Curculiginis Rhizoma on collagen induced arthritis was not revealed.Methods: Anti inflammatory effect of Curculiginis Rhizoma was researched in vitro with RAW264.7 cell and cell toxicity, levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-12) and PGE2 were analyzed by ELISA assay. Inflammatory protein were analyzed by western blotting assay (JNK, ERK, COX-2, TNF-α and IL-1β). In vivo, collagen induced arthritis mice model was used to evaluate anti-inflammation effect through arthritis index, immune cell number and cytokine levels (TNF-α, IL-6 and IL-1β) in serum.Results: ECR(Extract of Curculiginis Rhizoma) has not shown cell toxicity in 200 ㎍/㎖ on RAW264.7 cell. ECR suppressed releases of NO, TNF-α, IL-1β, IL-6, IL-12 and PGE2 on RAW264.7 cell treated with lipopolysacharide (1 ㎍/㎖). And ECR inhibited regulation of TNF-α, IL-1β and IL-6 mRNA, reduced protein release of JNK, ERK, iNOS, COX-2, IL-1β and TNF-α. AI of group treated with ECR 200 ㎎/㎏ and 100 ㎎/㎏ were significantly decreased compared to vihicle arthritis mice, the number of immune cell in foot joint was increased on control mice but those of group treated with ECR 200 ㎎/㎏ and 100 ㎎/㎏ were significantly reduced. This results correspond with contens of cytokines (TNF-α, IL-1β and IL-6) in serum.Conclusions: Curculiginis Rhizoma has anti-inflammation effect on RAW264.7 cell in vitro and collagen induced arthritis in vivo. So it is necessary to research more mechanism for cascade imfact.

• Journal of Microbiology and Biotechnology
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• v.32 no.1
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• pp.46-55
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• 2022

Clostridioides difficile infection (CDI) is a significant cause of hospital-acquired and antibiotic-mediated intestinal diseases and is a growing global public health concern. Overuse of antibiotics and their effect on normal intestinal flora has increased the incidence and severity of infections. Thus, the development of new, effective, and safe treatment options is a high priority. Here, we report a new probiotic strain, Bacillus amyloliquefaciens (BA PMC-80), and its in vitro/in vivo anti-C. difficile effect as a prospective novel candidate for replacing conventional antibiotics. BA PMC-80 showed a significant anti-C. difficile effect in coculture assay, and its cell-free supernatant (CFS) also exhibited a considerable anti-C. difficile effect with an 89.06 ㎍/ml 50% minimal inhibitory concentration (MIC) in broth microdilution assay. The CFS was stable and equally functional under different pHs, heat, and proteinase treatments. It also exhibited a high sensitivity against current antibiotics and no toxicity in subchronic toxicity testing in hamsters. Finally, BA PMC-80 showed a moderate effect in a hamster CDI model with reduced infection severity and delayed death. However, further studies are required to optimize the treatment condition of the hamster CDI model for better efficacy and identify the antimicrobial compound produced by BA PMC-80.