• Environmental Analysis Health and Toxicology
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• v.20 no.3 s.50
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• pp.243-248
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• 2005

Mancozeb (MCZ), a polymeric complex of zinr and manganese salts of ethylene bisthiocarbamate, is widely used in agriculture as fungicidel, insecticides, and herbicides. MCZ can be occupationally and environmentally exposed to human and has been reported to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine splenocytes through evaluation of splenocytes cellularity and INF-$\gamma$ synthesis. Splenocytes were examned ex vivo from mice orally treated with various doEes of MCZ for 1 day (acute exposure, 2,100, 5,000, 10,000 mg/kg) or ior 5 consecutive days per week for 4 weeks (subacute exposure,250, 1,000, 1,500 mg/kg/day) fellowed by culture for 2 days in the presence of Con A or PHA plus IL-2. Splenocytes Iron naive mice were cultured with various concentration of MCZ (50, 500, 1,000 ng/ml) in the presence of Con A or PHA plus IL-2 for 2 days in vitro. IFN-$\gamma$ production was decreased with the in vitro exposure to all concentration of MCZ. The spleen cellularity and IFN -$\gamma$ production by splenocytes from MCZ -acutely and - subacutely exposured mice were decreased in comparision with that oi control group.

• Journal of Applied Biological Chemistry
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• v.60 no.3
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• pp.241-244
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• 2017

The antioxidant activity of various solvent extracts from Jeju camellia mistletoe (Korthalsella japonica (Thunb.) Engl.) was investigated using various in vitro assays as the 1,1-diphenyl-2-picrylhydrazyl radical scavenging, ferrous ion chelating and reducing power assays. Methanol and ethanol extracts showed the most potent antioxidant activity in all assays tested followed by water extract. The inhibitory effect of the Jeju camellia mistletoe extracts on pancreatic lipase and $\acute{a}$-glucosidase was also evaluated and the results showed that methanol and ethanol extracts markedly reduced both enzyme activities. Therefore, the methanol and ethanol extracts of Jeju camellia mistletoe is definitely worthy of further investigation for these beneficial effects on nutraceutical medicine.

• Journal of Pharmacopuncture
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• v.25 no.3
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• pp.242-249
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• 2022

Objectives: The aim of this work is to evaluate the in vitro antioxidant, hypoglycemic, and antiobesity effects of Euphorbia resinifera extracts and investigate the phenolic constituents and the toxicity of these extracts. Methods: Phytochemical screening was performed to detect polyphenols and flavonoids. Antioxidant activity was evaluated by four methods (DPPH, ABTS, H₂O₂, and xanthine oxidase inhibition). The hypoglycemic effect was determined by the inhibition of α-amylase and α-glucosidase enzymes in vitro and via a starch tolerance study in normal rats. The antiobesity effect was estimated by in vitro inhibition of lipase. Results: Phytochemical screening revealed that the ethanolic extract was rich in polyphenols (99 ± 0.56 mg GEA/g extract) and tannins (55.22 ± 0.17 mg RE/g extract). Moreover, this extract showed higher antioxidant activity in different tests: the DPPH assay (IC₅₀ = 53.81 ± 1.83 ㎍/mL), ABTS assay (111.4 ± 2.64 mg TE/g extract), H₂O₂ (IC₅₀ = 98.15 ± 0.68 ㎍/mL), and xanthine oxidase (IC₅₀ = 10.26 ± 0.6 ㎍/mL). With respect to hypoglycemic effect, the aqueous and ethanolic extracts showed IC₅₀ values of 119.7 ± 2.15 ㎍/mL and 102 ± 3.63 ㎍/mL for α-amylase and 121.4 ± 1.88 and 56.6 ± 1.12 ㎍/mL for α-glucosidase, respectively, and the extracts lowered blood glucose levels in normal starch-loaded rats. Additionally, lipase inhibition was observed with aqueous (IC₅₀ = 25.3 ± 1.53 ㎍/mL) and ethanolic (IC₅₀ = 13.7 ± 3.03 ㎍/mL) extracts. Conclusion: These findings show the antioxidant, hypoglycemic, and hyperlipidemic effects of E. resinifera extracts, which should be investigated further to validate their medicinal uses and their pharmaceutical applications.

• Molecular & Cellular Toxicology
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• v.1 no.3
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• pp.179-188
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• 2005

To develop the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, VI-3, VII-3, VIII-3, VII-20 and VII-20 (sodium salt) were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Single cell gel electrophoresis (Comet) assay, mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay (MOLY), chromosomal aberration assay in mammalian cells and Ames reverse mutation assay in bacterial system were used as simplified, inexpensive, short-term in vitro screening tests in our laboratory. Through the primary screening using the comet assay, we could choose the first candidates of sophoricoside derivatives with no genotoxic potentials as JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt). Also JSH-VII-3, VII-20 and VII-20 (sodium salt) are non-mutagenic in MOLY assay, while JSH-II-3 is mutagenic at high concentration with the presence of metabolic activation system in both comet assay and MOLY assay. The selected derivatives (JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt) are not mutagenic in S. typhimurium TA98 and TA100 strains both in the presence and absence of metabolic activation. From results of chromosomal aberration assay, 6 h treatment of JSH-VI-3, VII-3 and VII-20 (sodium salt) were not revealed clastogenicity both in the presence and absence of S-9 mixture. Therefore, we suggests that JSH-VI-3, VII-3, VII-20 and VII-20 (sodium salt), as the optimal candidates with both no genotoxic potential and IL-5 inhibitory effects must be chosen. To process the development into new anti-inflammatory drug of these derivatives, further investigation will need.

• International Journal of Stem Cells
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• v.17 no.2
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• pp.120-129
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• 2024

Recent amendments to regulatory frameworks have placed a greater emphasis on the utilization of in vitro testing platforms for preclinical drug evaluations and toxicity assessments. This requires advanced tissue models capable of accurately replicating liver functions for drug efficacy and toxicity predictions. Liver organoids, derived from human cell sources, offer promise as a reliable platform for drug evaluation. However, there is a lack of standardized quality evaluation methods, which hinders their regulatory acceptance. This paper proposes comprehensive quality standards tailored for liver organoids, addressing cell source validation, organoid generation, and functional assessment. These guidelines aim to enhance reproducibility and accuracy in toxicity testing, thereby accelerating the adoption of organoids as a reliable alternative or complementary tool to animal testing in drug development. The quality standards include criteria for size, cellular composition, gene expression, and functional assays, thus ensuring a robust hepatotoxicity testing platform.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2004.05a
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• pp.87-87
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• 2004

• Environmental Analysis Health and Toxicology
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• v.14 no.1_2
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• pp.1-12
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• 1999

Recently, several new methods for the detection of genetic damages in vitro and in vivo based on molecular biological techniques were introduced according to the rapid progress in toxicology combined with cellular and molecular biology. Among these methods, mouse lymphoma thymidine kanase (tk) gene forward mutation assay, single cell gel electrophoresis (comet assay) and transgenic animal and cell line model as a target gene of lac I (Big Blue) and lac Z (Muta Mouse) gene mutation are newly introduced based on molecular toxicological approaches. The mouse lymphoma tk$\^$+/-/ gene assay (MOLY) using L5178Y tk$\^$+/-/ mouse lymphoma cell line is one of the mammalian forward mutation assays, and has many advantages and more sensitive than hprt assay. The target gene of MOLY is a heterozygous tk$\^$+/-/ gene located in 11 chromosome, so it is able to detect the wide range of genetic changes like point mutation, deletion, rearrangement, and mitotic recombination within tk gene or deletion of entire chromosome 11. The comet assay is a rapid, simple, visual and sensitive technique for measuring and analysing DNA breakages in mammalian cells, Also, transgenic animal and cell line models, which have exogenous DNA incorporated into their genome, carry recoverable shuttle vector containing reporter genes to assess endogenous effects or alteration in specific genes related to disease process, are powerful tools to study the mechanism of mutation in vivo and in vitro, respectively. Also in vivo acridine orange supravital staining micronucleus assay by using mouse peripheral reticulocytes was introduced as an alternative of bone marrow micronucleus assay. In this respect, there was an International workshop on genotoxicity procedure (IWGTP) supported by OECD and EMS (Environmental Mutagen Society) at Washington D. C. in March 25-26, 1999. The objective of IWGTP is to harmonize the testing procedures internationally, and to extend to finalization of OECD guideline, and to the agreement of new guidelines under the International Conference of Harmonization (ICH) for these methods mentioned above. Therefore, we introduce and review the principle, detailed procedure, and application of MOLY, comet assay, transgenic mutagenesis assay and supravital staining micronucleus assay.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 1996.12a
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• pp.61-61
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• 1996

Taxol is used as cancer therapeutic agent. It has been known as weak posotive of chromosome aberration assay in vitro in our previous results (Ryu et al., 1996) and potent clastogens in the mouse bone marrow micronucleus (Tinwell and Ashby, 1994). We performed microgel electrophoresis to determine the effect of taxol and it's precursor 10-deacetyl baccatin III(DAB) on DNA. Microgel electrophoresis is useful, rapid, simple, visual, and sensitive technique for measuring DNA breakage and repair mechanisms in mammalian 근ells. The range of concentration used for taxol were 854, 427, 213.5, 106.8, 53.4 Ug/ml, for DAB 910 ,455, 227.5 U9/ml, Cell viability always exceed 85%. We analyzed the results by using the special software of image analyzer for this comet assay (Komet 3.0). By using this image analyzer software , we can get the result as the tail moment ((mean of tail length - mean of head lengh) x tail%DNA/100). A slight increase in DNA migration was observed for taxol at the concentration of 854 Ug/m4 in the absence of S9 mixture. No increased DNA migration was observed after treatment with DAB.

• Toxicological Research
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• v.23 no.1
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• pp.47-53
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• 2007

Amygdalin is a cyanogenic glycoside which is commonly found in almonds, bamboo shoots, and apri-cot kernels, and peach kernels. Amygdalin was first hydrolysed into prunasin, then degraded into cyanohydrin by sequential two-stage mechanism. The objective of this study was to examine the amygdalin decomposition and cyanide formation at various in vitro conditions, including acid, enzyme and anaerobic microbes (AM) in human feces (HF). In acid hydrolysis mimicking gastric environment, amygdalin was degraded to cyanide up to 0.2% in specific pH. In contrast, enzyme assay showed higher cyanide generation either by ${\beta}$-glucosidase, or by incubation with microbe. In conclusion, we are convinced of cyanide generation are occurred mainly by microbiological activities of the gut flora up to 41.53%. After ingestion with some staff, the degree and site of degradation in an organism is a key parst of regulatory decision making of that staff.

• Journal of Microbiology and Biotechnology
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• v.25 no.4
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• pp.439-447
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• 2015

The objective of this study was to isolate and identify the chemical structure of a biosurfactant produced by Nocardia farcinica strain BN26 isolated from soil, and evaluate its in vitro antitumor activity on a panel of human cancer cell lines. Strain BN26 was found to produce glycolipid biosurfactant on n-hexadecane as the sole carbon source. The biosurfactant was purified using medium-pressure liquid chromatography and characterized as trehalose lipid tetraester (THL) by nuclear magnetic resonance spectroscopy and mass spectrometry. Subsequently, the cytotoxic effects of THL on cancer cell lines BV-173, KE-37 (SKW-3), HL-60, HL-60/DOX, and JMSU-1 were evaluated by MTT assay. It was shown that THL exerted concentration-dependent antiproliferative activity against the human tumor cell lines and mediated cell death by the induction of partial oligonucleosomal DNA fragmentation. These findings suggest that THL could be of potential to apply in biomedicine as a therapeutic agent.