• Biomolecules & Therapeutics
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• 제2권3호
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• pp.213-222
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• 1994

The acute tonicity of DWP305 (Ursodeoxycholic acid : Silymarin : Fursulthiamine : Riboflavin tetrabutyrate=1: 1 : 0.1 : 0.05) was evaluated in both sexes of Sprague-Dawley rats, 6weeks old by the oral route of administration. DWP305 was not considered to induce any toxic effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD$_{50}$ value in rats would be above 5 g/kg in the oral administration. Subacute toxicity of DWP305 was examined in Sprague-Dawley rats. Four groups of rats were administered orally at doses of 0, 0.32, 0.8, and 2.0 g/kg/day of DWP305 for one month. Any significant toxic clinical symptom was not observed in the treated rats during the experimental period. Macroscopic examination on the organs of tested animals showed no abnormal findings. On autopsy, no significant changes were found in organs examined. Maximum tolerated dose of DWP305 for the rat was estimated to be above 2 g/kg in this study.y.

• Journal of Microbiology and Biotechnology
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• 제21권12호
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• pp.1228-1235
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• 2011

We compared the gene expression among four clinical and five environmental V. vulnificus isolates, using a cDNA microarray containing 131 genes possibly associated with pathogenicity, transport, signal transduction, and gene regulations in the pathogen. cDNAs from total RNAs of these isolates were hybridized into the cDNA microarray using the cDNA of the wild-type strain MO6-24/O as a reference. We focused on selecting differentially expressed (DE) genes between clinical and environmental isolates using a modified t-statistic. We could detect two statistically significant DE genes between virulent isolates and less-virulent isolates with a marginal statistical significance (p-value of 0.008). These were genes putatively encoding pilin and adenlyate cylase. Real time-PCR confirmed that these two selected genes transcribed in significantly higher levels in virulent isolates than in less-virulent isolates. Mutants with lesions in the gene encoding pilin showed significantly higher $LD_{50}$ values than that of wild type.

• Molecular & Cellular Toxicology
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• 제5권2호
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• pp.153-159
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• 2009

In this study, we assessed the acute and subacute toxicity of Angelica gigas Nakai (A. gigas Nakai) extracts, which are comprised of decursin and decursinol angelate (D/DA) in rats. For the oral acute toxicity test, Sprague-Dawley (SD) male and female rats were gavaged with two doses of D/DA (200 and 2,000 mg/kg body weight) and then observed for any toxic symptoms for 2 weeks. The LD$_{50}$ value for the rats was greater than 2,000 mg/kg body weight for both male and female rats, which indicates that there were no toxic symptoms induced by doses of up to 2,000 mg/kg body weight. For the subacute toxicity study, rats were treated with D/DA at doses of 2 and 20 mg/kg body weight once a day for 30 days. There were no significant changes in body weight and food intake observed during the subacute toxicity study. In addition, no differences were observed between the control and treated groups when urinalysis was conducted or when hematology and biochemical parameters were evaluated. Finally, histopathological examination of the organs did not reveal any lesions in the control or treated groups. Taken together, these findings indicate that D/DA is safe and non-toxic.

• Journal of Preventive Medicine and Public Health
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• 제25권2호
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• pp.180-188
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• 1992

The effects of multiple exposures to pesticides on plasma cholinesterase(ChE) activities and urinary p-nitrophenol excretion were evaluated in rats. Rats were received single dose i.p. with $LD_{50}/100(mg/kg)$ of organophosphorous(OP), organophosphorous-organochroline(OP-OC), organophosphorous-carbamate(OP-CAB), organophosphorous-organoarsenate(OP-OA) pesticides for 4 consecutive days. In repeated administration of pesticides, plasma ChE activities were decreased, but urinary p-nitrophenol were increased after the first injection and then decreased gradually The recovery rates of ChE activities and p-nitrophenol excretion at 48 hours after the fourth Injection were delayed in comparision with the baseline value of 24 hours before the first injection. Statistical significances were found between OP and other groups except OP-OA group after the second injection in plasma ChE activities, but in urinary p-nitrophenol excretion there was statistical significance only between OP and OP-CAB.

• Toxicological Research
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• 제13권4호
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• pp.449-460
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• 1997

Single and 4 weeks oral administration of l-muscone, a major active ingredient of musk, to beagle dogs of both sexes were performed to investigate both acute and subacute toxicity. Beagle dogs(3 males and 3 females) in acute experiments were administered orally with single dosage of 2,000 mg/kg and groups of 9 male and 9 female beagle dogs in subacute experiments were given daily different dosage of l-muscone, 0.2 mg/kg/day(low dosage group), 2 mg/kg/day(middle dosage group), or 20 mg/kg/day(high dosage group) once a day for 4 weeks by oral route according to the Established Regulation of Korean Food and Drug Administration(1996.4.16). $LD_{50}$ value for beagle dogs was more than 2,000 mg/kg on oral route for both male and females. In animals administered with l-muscone, there were neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, eye examination, hematology, serum chemistry, organ weight and other findings. No histolopathological lesions were observed in both control and treatment groups. Above data strongly suggest that l-muscone in beagle dogs is considered to be safe.

• 생약학회지
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• 제49권3호
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• pp.246-254
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• 2018

Pectin lyase-modified red ginseng extract (GS-E3D) is a newly developed ginsenoside Rd-enriched ginseng extract. This study was designed to investigate the skin safety of GS-E3D. Single oral toxicity, single dermal toxicity, bovine corneal opacity and permeability (BCOP) assay, skin irritation test with $SkinEthic^{TM}$ human epidermis model, skin sensitization local lymph node assay, and human patch test, were examined. The oral and dermal $LD_{50}$ value of GS-E3D was over 2,000 mg/kg in rats. GS-E3D was identified as a non-irritant to skin in BCOP assay, human epidermis models, and patch test from the 32 human subjects. The skin sensitization potential of GS-E3D was less than 25% in local lymph node assay. These results indicate that GS-E3D can be used as a safe ingredient without adverse effects in various skin care products.

• Archives of Pharmacal Research
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• 제24권2호
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• pp.119-125
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• 2001

We have reported that kalopanaxsaponin A (KPS-A) Isolated from Kalopanax pictus have anti-rheumatoidal activity in the rat treated with Freunds complete adjuvant (FCA) reagent. In addition, it has been also reported that KPS-A is a potent antioxidant in the rheumatoidal rat. This research was undertaken to examine whether the saponins of KPS-A and -1 could adjust the abnormal lipid metabolisms and hematological changes in immunological diseases. KPS-A significantly inhibited the increases in both triglycerides and total proteins in addition to the decrease in total cholesterol induced by FCA reagent treatment. KPS-A treatment decreased the number of leucocytes elevated by FCA reagent treatment. Excess dose of the methanol extract produced no severe toxicity on the body weight, wet organ weights and hepatic functions. Since $LD_50$ value of K. pictus methanol extract was shown to be 4,033 ${mg/kg}$, it could be estimated to be a safe agent for anti-rheumatoidal herbal medicines.

• Animal cells and systems
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• 제1권4호
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• pp.637-640
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• 1997

Raf-1, a cytoplasmic serine/threonine protein kinase, serves as a central intermediate in many signaling pathways in cell proliferation, differentiation, and development. In this study, we investigated that B-raf, Drosophila homolog of the human c-raf-1, is involved in ultraviolet (UV) responsive events by using hypomorphic mutant $D-raf^{c110}$ and Draf-lacZ transgenic fly. At first, effect of UV damage on the survival of wild-type and $D-raf^{C110}$ strains was examined. In terms of $1/LD_{50}$ value, the relative ratio of UV sensitivities of wild-type versus $D-raf^{C110}$ strain was 1 : 2.2. By using quantitative $\beta$-galactosidase activity analysis, transcriptional activity of the D-raf gene promoter was also examined in UV-irradiated Draf-lacZ transgenic larvae. UV irradiation increased the expression of lacZ reporter gene in Draf-lacZ transgenic fly. However, in $D-raf^{C110}$ strain the transcriptional activity of D-raf gene promoter by UV irradiation was extensively reduced. Results obtained in this study suggest that D-raf plays a role in UV response, leading to better survival of Drosophila to UV damage.

• 농약과학회지
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• 제17권4호
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• pp.343-349
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• 2013

식물추출물 후추 추출물과 카시아 오일, 라벤더 오일을 이용하여 친환경유기농자재로 개발 중인 제품으로 배추좀나방 방제에 이용할 수 있는 후추 추출물+카시아 오일 57.5% (후보제형 A), 후추 추출물+카시아 오일 57% (후보제형 B), 후추 추출물+라벤더 오일 50% (후보제형 C) 유제의 생태에 대한 급성독성을 평가하여 친환경농자재 시제품으로서의 활용가능성을 확인하고자 하였다. 물벼룩 급성독성을 실시한 결과 후보제형 A 및 C 유제의 $EC_{50}$은 각 0.46, 0.25 mg $L^{-1}$로 EPA 기준으로 강한 독성이었고, 후보제형 B 유제의 $EC_{50}$는 1.9 mg $L^{-1}$로 보통독성이었다. 잉어 급성독성 시험의 경우, 후보제형 A 유제의 $LC_{50}$가 1.9 mg $L^{-1}$으로 농촌진흥청 고시에 따라 어독성 II급 농약이었으며 후보제형 B, C 유제는 2.9, 3.8 mg $L^{-1}$로 어독성 III급 농약으로 구분되었다. 꿀벌 급성독성시험은 접촉과 섭식 시험으로 나누어서 실시하였고, 후보 3종 모두 접촉과 섭식독성 $LD_{50}$가 100 ${\mu}g$ a.i $bee^{-1}$ 이상으로 나타나 독성이 낮은 것으로 판단되었다. 지렁이 급성독성시험의 경우, 후보제형 A, B 및 C 유제의 $LC_{50}$가 각각 887, 988, 564 mg $kg^{-1}$이었다. 후추 추출물+카시아 오일 57% (후보제형 B), 후추 추출물+라벤더 오일 50% (후보제형 C) 유제는 어독성 및 꿀벌 급성독성이 낮아 친환경 농자재로서 활용이 가능할 것으로 사료되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4331-4338
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• 2014

$N^1$-(2, 5-dimethoxyphenyl)-$N^8$-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of $RNHCO(CH_2)6CONHOH$ (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and $LD_{50}$. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations ($0.5-30{\mu}M$). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose-dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice ($LD_{50}$: 240.840mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.