• Title/Summary/Keyword: LD50

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Monoacylglycerol O-acyltransferase 1 (MGAT1) localizes to the ER and lipid droplets promoting triacylglycerol synthesis

  • Lee, Yoo Jeong;Kim, Jae-woo
    • BMB Reports
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    • v.50 no.7
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    • pp.367-372
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    • 2017
  • Monoacylglycerol acyltransferase 1 (MGAT) is a microsomal enzyme that catalyzes the synthesis of diacylglycerol (DAG) and triacylglycerol (TAG). However, the subcellular localization and catalytic function domain of this enzyme is poorly understood. In this report, we identified that murine MGAT1 localizes to the endoplasmic reticulum (ER) under normal conditions, whereas MGAT1 co-localize to the lipid droplets (LD) under conditions of enriching fatty acids, contributing to TAG synthesis and LD expansion. For the enzyme activity, both the N-terminal transmembrane domain and catalytic HPHG motif are required. We also show that the transmembrane domain of MGAT1 consists of two hydrophobic regions in the N-terminus, and the consensus sequence FLXLXXXn, a putative neutral lipid-binding domain, exists in the first transmembrane domain. Finally, MGAT1 interacts with DGAT2, which serves to synergistically increase the TAG biosynthesis and LD expansion, leading to enhancement of lipid accumulation in the liver and fat.

Fabrication and lasing characteristics of tunable Butt-coupled DBR-LD (Butt-coupled DBR-LD제작 및 동작특성)

  • 오수환;이철욱;김기수;이지면;고현성;박상기;박문호
    • Korean Journal of Optics and Photonics
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    • v.14 no.3
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    • pp.327-330
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    • 2003
  • We present the fabrication and measured performance of a wavelength tunable Butt coupled DBR-LD. An average coupling efficiency between active layer and passive waveguide layer was measured over 85%per facet, and the average threshold current was 21 ㎃ for the waveguide integrated DBR laser. High output power of Butt coupled DBR-LD was obtained over 25 ㎽. As high as 25 ㎽ of output power was achieved by the butt coupled method. The maximum wavelength tuning range is about 7.4 nm, and the side mode suppression ratio was more than 40 ㏈ using 1.3 ${\mu}{\textrm}{m}$ InGaAsP waveguide layer.

Experimental Study on Anti-body effects of Anti-BV on the Bee Venom Herbal Acupuncture (Anti-BV의 봉약침 항체 효능에 관한 실험적 연구)

  • Kwon, Ki-Rok;Lee, Kwang-Ho;Park, Won-Pil
    • Journal of Pharmacopuncture
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    • v.8 no.1
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    • pp.21-30
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    • 2005
  • Objectives : To observe physiological anti-body effects of anti-BV, acute toxic response, measurement of $LD_{50}$, and the effects of anti-body were evaluated. Methods : $LD_{50}$ of Anti-Bee Venom were measured, and to analyze acute toxic responses, weight, and the anti-body effects various concentrations of Anti-BV were diluted and the survival rate was measured. Cell blood count (CBC), liver, spleen, and kidney pathologies were observed from the histological aspects. Results : Experiment was conducted to observe Anti-BV as the anti-body to the bee venom and the following results were obtained : 1.anti-BV was injected intraperitoneally and no toxic responses were witnessed. All of the experiment subjects stayed alive during the experiment, making $LD_{50}$ analysis impossible. 2.Anti-BV was injected intraperitoneally in mice and no significant weight changes were measured between the control group and the experiment groups. 3. Measuring the concentration dependent survival rate, the highest survival rate was at the concentration of $1.25{\times}10^2mg/kg$(1/2.000) for Anti-BV. 4. No particular results were shown in the CBC test. 5. Observation of changes in the organ tissues, Anti-BV was found to suppress blood stasis in the liver and inhibit necrosis of the cells. Conclusion : Above results suggest that Anti-BV doesn't cause any toxic responses in the body and works as an anti-body to the bee venom. Further studies must be followed to secure the findings.

Single-Dose Oral Toxicity of the Gardenia Yellow Pigment in Rate and Rabbits (랫드 및 토끼에 대한 치자 황색색소에 관한 단회 투여 경구 독성 시험)

  • 김희구;이상준
    • The Korean Journal of Food And Nutrition
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    • v.11 no.1
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    • pp.77-81
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    • 1998
  • This study was performed to evaluate single-dose toxicity of the gardenia yellow pigment in Sprague-Dawley rats and New-Zealand White rabbits via oral routes. The yellow pigment was administered in rats at does levels of 5,000, 2,500, 1,250, 625, 312.5mg/kg and 9mg/kg. And also yellow pigment was administered in rabbits at does levels of 5,000, 2,500, 1,250mg/kg 0 unit /kg. The rats and rabbits of both sexes were observed daily for 14 days after single oral administration. Yellow pigment treated rats and rabbits did not induce any mortalities and abnormal signs in clinical findings, body weights, gross findings and histopathological finding. Based on these results, it is impossible to estimate LD50 values in rats and rabbits. Therefore, it was concluded that gardenia yellow pigment have no effect on acute toxicity and side effect in rats and rabbit.

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TOXICOLOGICAL EVALUATION OF ETHANOLIC EXTRACT FROM THE ROOT OF SCUTELLARIAE RADIX (황금(Scutellariae Radix)의 에타놀추출물과 프랄보노이드 성분들의 독성평가)

  • Chung, Chong-Pyoung;Ku, Young;Bae, Gi-Hwan
    • Journal of Periodontal and Implant Science
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    • v.25 no.3
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    • pp.470-477
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    • 1995
  • Flavonoids from Scutellariae Radix possessed a dual function both as an anti-inflammatory agent and an enhancer of cellular activity in gingival fibroblast. The purpose of this study was to evaluate on the toxicity of ethanolic extract from the root of Scutellariae Radix Georgi and its flavonoids, Wogonin, Baicalein, and Baicalin were isolated and purified by the following method. The crude drug was extracted with ethyl acetate and the residue was dissolved in ethyl alcohol. The ethyl alcohol soluble fraction was separated, concentrated, and then chromatographed on a silica gel column. The acute oral LD 50 in rats was determined for EtOH ex. of Scutellariae Radix and three compounds were evaluated with a single oral gavage at three graded dosage levels. The acute intravenous LD 50 was determined with a single intravenous injection via the jugular vein at three graded dosage levels. Groups of 5 male and 5 female rats, 6 week of age at the start of the study, were fed diets containing 3 graded dosage levels for 14 days. Groups of 5 male and 5 female hamster received O.5ml of the test article at once in a day for 5 days to the buccal cheek pouch for two minutes each. The acute oral LD50 for EtOH ex. of Scutellariae Radix is 1430mg/kg, and for Wogonin 1320mg/kg, for Baicalein 1250mg/kg, for Baicalin 1330mg/kg. The acute intravenous toxicity of EtOH ex. of Scutellariae Radix and its extracts was found to be 27mg/kg body weight No toxic effects were observed in rats fed up to 200mg/kg of EtOH ex. of Scutellariae Radix, Wogonin, Baicalein and Baicalin in the diet for 14 days. The acute Mucouse Membrane LD 50 in hamsters was found to be greater than 100mg/kg. These results suggested that EtOH ex. of Scutellariae Radix and its flavonoids are safe for oral care products using limited amount of extract.

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Studies on the Liver Toxicities with different Dosage of Wild Aconiti Tuber Decoction (임상투여용량에서 초오전탕액의 흰쥐에 대한 간독성연구)

  • Kim, Yun-Kyung;Lee, Je-Hyun;Song, Kye-Yong;Park, Seong-Kyu;Kim, Chung-Sook
    • Herbal Formula Science
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    • v.13 no.1
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    • pp.123-143
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    • 2005
  • Objective : This study was carried out to evaluate the liver toxicities of Wild Aconiti Tuber decoction. Methods : The amounts of aconitine in the methanol extract of Wild Aconiti Tuber was measured by HPLC. Safeties was studied by LD50 in mice. Liver toxicities were evaluated histologically and by CBC, blood chemistry after 2 weeks of 0.4g/kg/day clinical dosage oral administrations in rat. Results : 1. The amounts of aconitine in the methanol extract of Wild Aconiti Tuber is $1.697{\pm}0.052mg/g$. But aconitine was not detected in the water decoction of Wild Aconiti Tuber. 2. To evaluate LD50 and safeties of Wild Aconiti Tuber decoction, ICR mice were given high dose of 2, 5, 10g/kg for single time and were observed for 2 weeks. There were no dead animal and abnormal clinical sign and no abnormalities at the autopsy. So, LD50 was admitted to higher than 10g/kg. 3. After 2 weeks of 0.4g/kg/day clinical dosage oral administrations in rat, there was no significant change in the CBC and blood chemistry. 4. In the liver tissues of clinical dosage, mitotic figures, apoptosis and individual cell death were observed, but clear liver toxicities like fatty liver or necrosis were not observed. the liver tissues of high dose in mice, hydropic changes were getting severe as dose grows. Conclusions : According to the results, though aconitine was not detected in the Wild Aconiti Tuber decoction, 0.4g/kg/day 2 weeks p. o (clinical dosage) group showed weak changes in the liver tissues and high dose group showed liver toxicities like hydropic changes.

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Changes in Glucose Concentrations and Activities of Cholinesterase in Serum, Brain and Spinal cord in Mice following Orally Administration of Parathion (Parathion을 경구투여한 Mouse의 체내 Cholinesterase 활성도 및 Glucose함량 조사)

  • 도재철;이창우;차우양;손재권;정종식
    • Korean Journal of Veterinary Service
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    • v.15 no.1
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    • pp.58-66
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    • 1992
  • The insecticide p-nitropheny diethyl thiophospate is alse known by the symbol E.605 and a legion of trade names including “parathion”. The insecticide is widely used in agriculture, but it is highly toxic and now clear that parathion behaves like a cholinergic drug by inhibiting the enzyme cholinesterase. In order to know acute toxicity and the changes of glucose concentrations and activity according to time lapsed in female mice given orally single with the half dose to $LD_{50}$ of parathion, glucose contents and cholinesterase activities in serum as well as cholinesterase activities in whole brain and spinal cord were investigated, otherwise median lethal dose ($LD_{50}$) of parathion given orally against female mice was determined. The results obtained were summerized as follows ; 1. $LD_{50}$ value of parathion given orally to female mice was 7.1mg/kg(95% confidence limits, 3.8-13.1mg/kg) 2. The inhibition rate of cholinesterase activities in serum of parathion-administrated mice according to time lapsed were peakly decreased to 61% after 30 minutes in comparison to control group, but activities were completely recovered after 48 hours. 3. The inhibition rate of cholinesterase activities in whole brain of parathion-administrated mice according to time lapsed were peakly decreased to 49% after 2 hours in completely recovered after 24 hours. 4. The inhibition rate of cholinesterase activities in spinal cord of parathion-administrated mice according to time lapsed were peakly decreased to 57% after 2 hours in comparison to control group, but activities were completely recovered after 48 hours. 5. The changes of glucose contents in serum of parathion-administrated mice according to time lapsed and in directly after death due to parathion poisoning were no significantly difference.

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Study on the Chemical Management - 2. Comparison of Classification and Health Index of Chemicals Regulated by the Ministry of Environment and the Ministry of the Employment and Labor (화학물질 관리 연구-2. 환경부와 고용노동부의 관리 화학물질의 구분, 노출기준 및 독성 지표 등의 특성 비교)

  • Kim, Sunju;Yoon, Chungsik;Ham, Seunghon;Park, Jihoon;Kim, Songha;Kim, Yuna;Lee, Jieun;Lee, Sangah;Park, Donguk;Lee, Kwonseob;Ha, Kwonchul
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.25 no.1
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    • pp.58-71
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    • 2015
  • Objectives: The aims of this study were to investigate the classification system of chemical substances in the Occupational Safety and Health Act(OSHA) and Chemical Substances Control Act(CSCA) and to compare several health indices (i.e., Time Weighted Average (TWA), Lethal Dose ($LD_{50}$), and Lethal Concentration ($LC_{50}$) of chemical substances by categories in each law. Methods: The chemicals regulated by each law were classified by the specific categories provided in the respective law; seven categories for OSHA (chemicals with OELs, chemicals prohibited from manufacturing, etc., chemicals requiring approval, chemicals kept below permissible limits, chemicals requiring workplace monitoring, chemicals requiring special management, and chemicals requiring special heath diagnosis) and five categories from the CSCA(poisonous substances, permitted substances, restricted substances, prohibited substances, and substances requiring preparation for accidents). Information on physicochemical properties, health indices including CMR characteristics, $LD_{50}$ and $LD_{50}$ were searched from the homepages of the Korean Occupational and Safety Agency and the National Institute of Environmental Research, etc. Statistical analysis was conducted for comparison between TWA and health index for each category. Results: The number of chemicals based on CAS numbers was different from the numbers of series of chemicals listed in each law because of repeat listings due to different names (e.g., glycol monoethylether vs. 2-ethoxy ethanol) and grouping of different chemicals under the same serial number(i.e., five different benzidine-related chemicals were categorized under one serial number(06-4-13) as prohibited substances under the CSCA). A total of 722 chemicals and 995 chemicals were listed at the OSHA and its sub-regulations and CSCA and its sub-regulations, respectively. Among these, 36.8% based on OSHA chemicals and 26.7% based on CSCA chemicals were regulated simultaneously through both laws. The correlation coefficients between TWA and $LC_{50}$ and between TWA and $LD_{50}$, were 0.641 and 0.506, respectively. The geometric mean values of TWA calculated by each category in both laws have no tendency according to category. The patterns of cumulative graph for TWA, $LD_{50}$, $LC_{50}$ were similar to the chemicals regulated by OHSA and CCSA, but their median values were lower for CCSA regulated chemicals than OSHA regulated chemicals. The GM of carcinogenic chemicals under the OSHA was significantly lower than non-CMR chemicals($2.21mg/m^3$ vs $5.69mg/m^3$, p=0.006), while there was no significant difference in CSCA chemicals($0.85mg/m^3$ vs $1.04mg/m^3$, p=0.448). $LC_{50}$ showed no significant difference between carcinogens, mutagens, reproductive toxic chemicals and non-CMR chemicals in both laws' regulated chemicals, while there was a difference between carcinogens and non-CMR chemicals in $LD_{50}$ of the CSCA. Conclusions: This study found that there was no specific tendency or significant difference in health indicessuch TWA, $LD_{50}$ and $LC_{50}$ in subcategories of chemicals as classified by the Ministry of Labor and Employment and the Ministry of Environment. Considering the background and the purpose of each law, collaboration for harmonization in chemical categorizing and regulation is necessary.

Acute toxicity response caused by mixture or tank mix of several insecticides (몇 가지 살충제의 혼용 및 혼합 시 독성반응)

  • Lee, Je-Bong;Jeong, Mi-Hye;Sung, Ha-Jung;Lee, Hae-Keun;Yang, Jae-Sul
    • The Korean Journal of Pesticide Science
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    • v.5 no.4
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    • pp.57-61
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    • 2001
  • Tank mixing application of pesticides has been used to reduce labor and to control wide spectrum of pests, but it may cause significant pesticide poisoning on human and animals due to carelessness. The toxic response of pesticides for the tank mixtures and mixtures was investigated to determine acute toxicity and enzymatic change using experimental animals. Acute oral toxicity and acute dermal toxicity were tested by RDA test guideline. The $LD_{50}$ was calculated by probit analysis method and cholinesterase was measured with automatic analyzer. The toxicities were generally higher than estimated toxicities in tank mixing and mixture. Serum cholinesterase activity was inhibited more than expected at the dose levels of 1/5, 1/10 and 1/20 of $LD_{50}$. Therefore, the results of this study showed that acute toxicity caused by the pesticide mixtures should be considered before the tank mixing method is applied.

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Evidence-based approach for herbal medicine-safety classification : Human equivalent dose-based the margin of safety (한약의 안전성 등급화를 위한 evidence-based approach : Human equivalent dose-based the margin of safety)

  • Park, Yeong-Chul;Lee, Sundong
    • Journal of Society of Preventive Korean Medicine
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    • v.17 no.3
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    • pp.19-30
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    • 2013
  • This study was aimed to develop a new formula for herbal medicine-safety classification in terms of evidence-based medicine. Recently, human equivalent dose(HED)-based therapeutic index was developed for herbal medicine-safety classification by transforming $LD_{50}$ to HED. However, the use of the $ED_{50}$ and $LD_{50}$ to derive the therapeutic index may be misleading as to safety, depending on the slope of the dose-response curves for therapeutic and lethal effects. To overcome this deficiency, HED-based MOS(Margin of Safety)was developed and suggested in this study. The HED-based MOS developed by using $LD_1$, changing to ALD(approximate lethal dose), and $ED_{99}$. The HED-based MOS seems to be more useful and safer than HED-based therapeutic index since its values for several herbal medicines are basically two times less than the values from HED-based therapeutic index. Thus, HED-based MOS can be a good example of Evidence-based approach for herbal medicine-safety classification.