• Title/Summary/Keyword: 일반독성

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A Comparative Study on the Two Different Doses of Dexrazoxane (덱스라족산의 두 가지 다른 용량의 비교 연구)

  • Rhew, Ki-Yon
    • Korean Journal of Clinical Pharmacy
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    • v.20 no.3
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    • pp.248-254
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    • 2010
  • 본 연구에서는 anthracyclines의 심장 독성을 예방하기 위해 사용되는 dexrazoxane의 가장 적절하고 안전한 용량을 평가하고자 했다. 이 약물은 같은 적응증에도 불구하고 미국과 유럽에서 두 배 차이가 나는 용량으로 허가 받아 사용되고 있다. 그러므로 dexrazoxane의 anthracycline로 인한 심독성의 예방에 관한 논문을 찾아 dexrazoxane : doxorubicin = 20:1의 비율로 사용했을 경우와 10:1로 사용했을 때의 효과와 부작용을 비교하였다. 이 두 가지 용량으로 진행된 모든 임상 연구에서 dexrazoxane이 doxorubicin의 심독성 예방에 통계적으로 유효한 효과가 있다고 결론 내렸다. 또한 dexrazoxane의 추가 요법으로 인해 Tumor effect의 차이를 비교 분석한 결과, 두 가지 용량 모두에서 dexrazoxane이 doxorubicin의 항암 효과에 영향을 미치지 않는 것으로 분석되었다. 대부분의 연구에서 dexrazoxane의 약물 자체의 부작용은 분석하지 않았지만, dexrazoxane:doxorubicin을 20:1의 비율로 사용했던 한 연구에서 dexrazoxane군에서 부작용이 있음이 평가되었다. 반면, dexrazoxane의 용량을 doxorubicin 용량에 비해 10:1로 사용한 모든 연구는, 대상 환자군이 18세 이하의 소아 청소년으로 이 용량을 성인에게도 적용할 수 있는지에 대한 추가 연구가 필요하다. 그러나 항암제의 경우, 대부분 환자의 체표면적(BSA)을 기준으로 약용량을 결정하며, 이는 일반적으로 10세 이상이 되면 어른의 체표면적의 70% 정도가 된다. 그러므로, 본 연구에서는 통계적으로 충분한 수의 10세 이상의 소아, 청소년에게 doxorubicin으로 인한 심독성 예방 효과가 입증되었던 dexrazoxane: doxorubicin을 10:1의 용량으로 사용하여도 임상적인 효과를 기대 할 수 있으며, 이 용량은 dexrazoxane 자체의 유해반응도 감소시킬 수 있을 것이라고 결론 맺는다.

Lethal Toxicity and Hematological Changes Exposed to Nitrate in Flatfish, Paralichthys olivaceus in Biofloc and Seawater (바이오플락 및 일반 해수에서 질산염의 넙치 (Paralichthys olivaceus)에 미치는 급성 독성 및 혈액학적 성상의 변화)

  • Bae, Sun-Hye;Kim, Ki Wook;Kim, Su Kyoung;Kim, Su-Kyoung;Kim, Jong-Hyun;Kim, Jun-Hwan
    • Korean Journal of Environmental Biology
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    • v.35 no.3
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    • pp.373-379
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    • 2017
  • Juvenile Paralichthys olivaceus (mean length $19.8{\pm}2.6cm$, mean weight $97.8{\pm}15.8g$) were exposed for 96 hours to different nitrate concentrations of 0, 62.5, 125, 250, 500, 1,000, and $1,500mg\;L^{-1}$ in biofloc and 0, 62.5, 125, 250, 500, and $1,000mg\;L^{-1}$ in seawater. Median lethal concentration values ($LC_{50}$, the concentration at which 50% of mortality occurred after 96 hours of exposure) of nitrate to P. olivaceus in biofloc and seawater were 1,226 and $597mg\;NO_3L^{-1}$ (P<0.05), respectively, revealing a higher toxicity of nitrate to P. olivaceus in seawater than in biofloc. In hematological parameters, hematocrit level in P. olivaceus exposed to nitrate was significantly increased only at a concentration of $1,000mg\;L^{-1}$ in biofloc and at concentrations higher than $250mg\;L^{-1}$ in seawater, but no significant changes in hemoglobin were found in biofloc and seawater. In plasma parameters, aspartate aminotransferase (AST) and alanine aminotransminase (ALT) were significantly increased by nitrate exposure in biofloc and seawater, but no significant changes in alkaline phosphatase (ALP) were found in biofloc and seawater. Results of this study indicate that nitrate exposure to P. olivaceus have a lethal toxic effect and alter hematological and plasma constituents of flatfish P. olivaceus. Given relatively lower toxicity of nitrate in biofloc than in seawater, the use of biofloc in aquaculture may reduce potential toxic effect caused by nitrate in feces and feed residue.

Analysis of Toxicity in Escherichia coli from the Expression of Human Purinergic Receptor $P2X_4$ (인간 퓨린수용체 $P2X_4$를 발현시킬 때 나타나는 대장균 독성의 원인분석)

  • Yu, Yon-Joo;Jung, Yun-A;Lim, Dong-Bin
    • Korean Journal of Microbiology
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    • v.47 no.1
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    • pp.7-13
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    • 2011
  • In general, expression of membrane protein in Escherichia coli is very toxic to the host organism, but the mechanism for the toxicity is not clear yet. Expression of human purinergic receptor $P2X_4$ was found to be extremely toxic to the host E. coli. We examined this toxicity by isolation and analysis of less toxic mutant proteins. We could isolate 30 less toxic mutants of $P2X_4$ after hydroxylamine mutagenesis. Western blot showed that all of them produced proteins smaller than the wild type $P2X_4$. DNA sequencing of two largest mutant proteins showed that they were lost its second transmembrane domain. Localization analysis of these mutant proteins showed that they are not in cytoplasmic membrane, but in inclusion bodies. These data showed that inactive truncated $P2X_4$ is not toxic to E. coli and membrane integration and functionality of $P2X_4$ may be needed to show host toxicity.

Effects of High-fat Diet on Type-I Muscle Loss in Rats (고지방식이가 쥐의 Type-I 근육손실에 미치는 영향)

  • Baek, Kyung-Wan;Cha, Hee-Jae;Park, Jung-Jun
    • Journal of Life Science
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    • v.23 no.12
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    • pp.1509-1515
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    • 2013
  • The term lipotoxicity has been used to describe how excess lipid accumulation leads to cellular dysfunction and death in non-adipose tissues, including skeletal muscle. While lipotoxicity has been found in cultured skeletal muscle cells with high-fat feeding, the consequences of lipotoxicity in vivo are still unknown, particularly in Type-I muscle, which is metabolically affected by lipotoxicity. The aim of this study was to investigate the effects of a high-fat diet on changes in the morphology and apoptotic protein expression of Type-I muscle loss in rats. The rats were fed either a high-fat diet or a normal diet for six weeks, and then lipid accumulation, inflammation response, and nucleus infiltration were measured, and PARP protein expression was cleaved by Oil Red O staining, H & E staining, and Western blot, respectively. Lipid accumulation, inflammation response, nucleus infiltration, and cleaved PARP protein expression were significantly (p<0.05) higher in the high-fat diet group than they were in the normal diet group. The weight of Type-I muscle tended to be lower in the high-fat diet group compared to the normal diet group, but the difference was not statistically significant. These results indicate that a high-fat diet triggers cell death in Type-I muscle via lipotoxicity, which suggests that a high-fat diet may be associated with sarcopenia.

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.

Biochemical Assessment of Deer Velvet Antler Extract and its Cytotoxic Effect including Acute Oral Toxicity using an ICR Mice Model (ICR 마우스 모델을 이용한 녹용 추출물의 생화학적 평가 및 급성 경구 독성을 포함한 세포 독성 효과)

  • Ramakrishna Chilakala;Hyeon Jeong Moon;Hwan Lee;Dong-Sung Lee;Sun Hee Cheong
    • Journal of Food Hygiene and Safety
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    • v.38 no.6
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    • pp.430-441
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    • 2023
  • Velvet antler is widely used as a traditional medicine, and numerous studies have demonstrated its tremendous nutritional and medicinal values including immunity-enhancing effects. This study aimed to investigate different deer velvet extracts (Sample 1: raw extract, Sample 2: dried extract, and Sample 3: freeze-dried extract) for proximate composition, uronic acid, sulfated glycosaminoglycan, sialic acid, collagen levels, and chemical components using ultra-performance liquid chromatography-quadrupole-time-of-light mass spectrometry. In addition, we evaluated the cytotoxic effect of the deer velvet extracts on BV2 microglia, HT22 hippocampal cells, HaCaT keratinocytes, and RAW264.7 macrophages using the cell viability MTT assay. Furthermore, we evaluated acute toxicity of the deer velvet extracts at different doses (0, 500, 1000, and 2000 mg/kg) administered orally to both male and female ICR mice for 14 d (five mice per group). After treatment, we evaluated general toxicity, survival rate, body weight changes, mortality, clinical signs, and necropsy findings in the experimental mice based on OECD guidelines. The results suggested that in vitro treatment with the evaluated extracts had no cytotoxic effect in HaCaT keratinocytes cells, whereas Sample-2 had a cytotoxic effect at 500 and 1000 ㎍/mL on HT22 hippocampal cells and RAW264.7 macrophages. Sample 3 was also cytotoxic at concentrations of 500 and 1000 ㎍/mL to RAW264.7 and BV2 microglial cells. However, the mice treated in vivo with the velvet extracts at doses of 500-2000 mg/kg BW showed no clinical signs, mortality, or necropsy findings, indicating that the LD50 is higher than this dosage. These findings indicate that there were no toxicological abnormalities connected with the deer velvet extract treatment in mice. However, further human and animal studies are needed before sufficient safety information is available to justify its use in humans.

중추신경계 작용약물의 자발운동 양상에 미치는 영향

  • 박찬웅
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.169-169
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    • 1993
  • 동물의 일반활동은 중추신경계에 작용하는 약물에 관한 많은 정보를 제공한다. 따라서 약물의 중추신경계에 대한 독성평가는 물론이고 중추신경계 작용약물의 검색에도 널리 이용된다. 본 연구에서는 여러 가지 기전으로 중추신경계에 작용하는 약물들의 일반활동을 분석하여 중추신경계 작용 약물들의 작용기전에 따르는 일반활동의 특성을 비교 분석하고자 하였다. 실험장치는 UGO BASILE제 활동측정 장치를 이용하였으며, 실험동물은 서울대학교 의과대학 실험동물 사육장에서 사육한 ICR mouse를 사용하였다. 동물의 활동측정은 환경요인을 최소한으로 배제하기 위하여 매일 9:00-11:00 까지 2시간 동안의 행동을 10분 간격으로 측정 기록토록 하였다. 중추신경 흥분제 amphetamine, 진정수면제 phenobarbital, 항불안제 diazepam, 항정신병약 chlorpromazine, 항우울제 haloperidol는 모두 용량 의존적으로 동물의 자발운동에 영향을 미쳤다. 특기할 것은 항불안제 diazepam 은 용량의존적으로 운동 억제를 나타내었으나 진정수면제 phenobarbital의 경우는 용량 의존전 운동억제를 나타내기 이전에 초기약물 유발성 aggressive behavior를 나타내었다. 본 실험결과는 동물의 자발행동의 분석으로 중추신경계 작용약물의 작용기전 규명 및 이에 따르는 약물의 분류 방법으로 유용하게 이용될 수 있을 것으로 생각된다.

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Optimization of Enzymatic Hydrolysis for the Production of Antitoxic Bovine Hepatic Extract (항독성 소간추출물의 생산을 위한 효소분해의 최적화)

  • Kim, Hyun-Jung;Kwon, Do-Hyeong;Shon, Dong-Haw
    • Korean Journal of Food Science and Technology
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    • v.40 no.2
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    • pp.190-193
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    • 2008
  • Bovine hepatic extract is recognized as possessing detoxifying activity against various liver diseases. In orderto develop a process for its mass production, various enzymatic hydrolysis conditions were tested, and bovine hepatic extracts were prepared. These extracts were then examined for composition, microorganism levels, and vitamin $B_{12}$ content. Among the enzymes tested, papain was selected based on yields for dry residue and amino nitrogen. The other enzymes tested included bromelain, ficin, pancreatin, and protease NP. The optimal hydrolysis conditions were established at 65$^{\circ}C$ for 24 hr, with an addition of 1%(w/w) papain to the beef liver. The prepared spray-dried bovine hepatic extract showed an 11% recovery yield on a raw beef liver basis, with 95% dry residue and 11.8% total nitrogen content. Microorganisms were not detected in the dried extract, and its vitamin $B_{12}$ content was 4.1 ${\mu}$g/g. In summary, the conditions established in this study could be applied for the high yield mass production of bovine hepatic extract.

Toxicity Assessment and Evaluation of the Applicability of a Constructed Wetland of Bio-reeds and Bio-ceramics (바이오갈대와 바이오여재를 적용한 인공습지의 효율성 및 독성평가)

  • Park, Da Kyung;Chang, Soon-Woong;Choi, Hanna
    • Korean Journal of Environmental Biology
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    • v.35 no.4
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    • pp.654-661
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    • 2017
  • Recently, a low-impact development (LID) technic such as a wetland has been proposed as a Nature-friendly process for reducing pollutants caused by livestock wastewater. Therefore, the Daphnia magna toxicity was analyzed for livestock wastewater samples, to determine if a wetland system would also be effective in reducing this ecotoxicity. In the present study, acute D. magna toxicity was not significantly dependent on the presence and type of reed, nor type of media. However, when treated with construction wetlands, ecotoxicities decreased as well as TN, TP and COD concentrations. Therefore, it is considered that a construction wetland system with bio reeds and bio-media as well as general reeds would be effective to reduce the ecotoxicity of livestock wastewater. To apply a wetland system as the subsequent treatment process to a livestock waste water treatment facility, it is necessary to perform an integrated evaluation such as treatment efficiency and the ecotoxicity test for various characteristics of livestock wastewater.

Acute Toxicity of Bovine Somatotrophine-Sustained Release(BST-SR) in Rats and Mice (랫드와 마우스에서 소성장 호르몬-서방형 제형(BST-SR)의 급성독성에 관한 연구)

  • 강경선;이영순
    • Journal of Food Hygiene and Safety
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    • v.6 no.3
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    • pp.185-189
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    • 1991
  • This study was carried out to investigate whether acute toxicity of BST-SR is or not. Single dose of BST-SR was given to both sexes of Spraqe-Dawley rats and ICR mice, subcutaneously. No significant toxic symptom was observed in single treated rats and mice during the experimental period. In gross and microscopic observation, no significantly different abnormality observed between the several organs of tested animals and control animals. Therefore, it was concluded that BST-SR was nontoxic when BST-SR was subcutaneously administered to rats and mice up to 1000 times of clinical dose.

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