• 제목/요약/키워드: P-S-R

검색결과 8,993건 처리시간 0.044초

Antitumor Activity of 7-[2-(N-Isopropylamino)ethyl]-(20s)-camptothecin, CKD602, as a Potent DNA Topoisomerase I Inhibitor

  • Lee, Jun-Hee;Lee, Ju-Mong;Kim, Joon-Kyum;Ahn, Soon-Kil;Lee, Sang-Joon;Kim, Mie-Young;Jew, Sang-Sup;Park, Jae-Gab;Hong, Chung-Il
    • Archives of Pharmacal Research
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    • 제21권5호
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    • pp.581-590
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    • 1998
  • We developed a novel water-soluble camptothecin analobue, CKD602, and evaluated the inhibition of topoisomerase I and the antitumor activities against mammalian tumor cells and human tumor xenografts. CKD602 was a nanomolar inhibitor of the topoisomerase I enzyme in the cleavable complex assay. CKD602 was found to be 3 times and slightly more potent than topotecan and camptothecin as inhibitors of topoisomerase, respecitively. In tumor cell cytotoxicity, CKD602 was more potent than topotecan in 14 out of 26 human cancer cell lines tested, while it was comparable to camptothecin. CKD602 was tested for the in vivo antitumor activity against the human tumor xenograft models. CKD602 was able to imduce regression of established HT-29, WIDR and CX-1 colon tumors, LX-1 lung tumor, MX-1 breast tumor and SKOV-3 ovarian tumor as much as 80, 94, 76, 67, 87% and 88%, respectively, with comparable body weight changes to those of topotecan. Also the therapeutic margin (R/Emax: maximum tolerance dose/$ED-{58}$) of CKD602 was significantly higher than that of topotecan by 4 times. Efficacy was determined at the maximal tolerated dose levels using schedule dependent i.p. administration in mice bearing L1210 leukemia. On a Q4dx4 (every 4 day for 4 doses) schedule, the maximum tolerated dose (MTD) was 25 mg/kg per administration, which caused great weight loss and lethality in <5% tumor bearing mouse. this schedule brought significant increase in life span (ILS), 212%, with 33% of long-term survivals. The ex vivo antitumor activity of CKD602 was compared with that of topotecan and the mean antitumor index (ATI) values recorded for CKD602 were significantly higher than that noted for topotecan. From these results, CKD602 warrants further clinical investigations as a potent inhibitor of topoisomerase I.

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아라키돈산과 철 유도성 산화적 스트레스에 대한 금앵자(金櫻子) 열수 추출물의 간세포 보호 효능 (Water Extract of Rosa laevigata Michx. Protects Hepatocytes from Arachidonic Acid and Iron-mediated Oxidative Stress)

  • 고해리;제갈경환;송시연;김난이;강지원;변성희;김영우;조일제;김상찬
    • 대한본초학회지
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    • 제30권6호
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    • pp.7-15
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    • 2015
  • Objectives : Rosa laevigata Michx. has been used for the treatment of renal disease in traditional Korean medicine. In this study, we investigated cytoprotective effect of R. laevigata water extract (RLE) against oxidative stress induced by arachidonic acid (AA) + iron.Methods : To evaluate the protective effects of RLE against AA + iron-induced oxidative stress in HepG2 cell, cell viability and changes on apoptosis-related proteins were assessed by MTT and immunoblot analyses. The effects of RLE on reduced glutathione level, production of reactive oxygen species and mitochondrial membrane potential were also monitored. Furthermore, to verify underlying molecular mechanism, NF-E2-related factor 2 (Nrf2) was examined by immunoblot analysis. Additionally, Nrf2 transactivation and its downstream target genes expression were also determined by reporter gene and realtime RT-PCR analyses.Results : RLE pretreatment (30-300 μg/ml) prevented cells from AA + iron-mediated cell death in a concentration dependent manner. In addition, 100 μg/ml RLE inhibited AA + iron-induced glutathione depletion, reactive oxygen species production and mitochondrial dysfunction. RLE accumulated nuclear Nrf2 and also transactivated Nrf2, which was evidenced by antioxidant response element- and glutathione S-transferase A2-driven luciferase activities and mRNA level of glutamate-cysteine ligase catalytic subunit, NAD(P)H:quinone oxidoreductase 1 and sestrin 2. Moreover, protective effect of RLE against AA + iron was abolished in Nrf2 knockout cells.Conclusions : These results indicate that RLE has the ability to protect hepatocyte against oxidative stress through Nrf2 activation.

유료노인전문요양원 입주의사 결정요인에 관한 연구 (Factors Influencing the Intention of Admission into a Charged Nursing Home for the Elderly)

  • 유영순;조은희;유병철;정귀원;엄상화;김성준;전진호
    • Journal of Preventive Medicine and Public Health
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    • 제34권1호
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    • pp.1-8
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    • 2001
  • Objectives : To gather information about the factors which influence the interest and intention of admission into charging nursing hones for the elderly(CNH), as these homes represent an important method for resolving the problems related to the rapid population aging occurring in Korea. Methods : A face-to-face interview survey was carried out with 320(men 159, women 165) patients over 60 years old who were admitted at 2 university hospitals and 5 general hospitals in the Busan area between December 1998 and March 1999. Data were analyzed through t-test, ANOVA, correlation and multiple regression analysis. Results : The mean age and years of education of the study population was 67.0 and 7.7 years, and the types of chronic degenerative disease included musculoskeletal disorders(20.1%), cerebrovascular disease(17.1%), and diabetes(14.3%). The major forms of household living arrangement prior to admission were elderly alone(22.6%), and elderly couple(33.5%), while about half of them(55.5%) didn't want to live with their children id the future. Almost half were paying medication fees by themselves(46.6%). The level of actual intention of admission$(3.07{\pm}1.39)$ into a CNH was lower than that of interest$(3.22{\pm}1.33)$(p<0.01). Multiple analysis revealed that the intention of admission increased with decreasing number of future supportive persons$(\beta=-0.107)$, lower level of activity in daily life$(\beta=-0.447)$, and longer years of education$(\beta=-0.447)$ with 32.7% of $R^2$. As for the factors which determined the admission into a CNH, the fee and facilities were considered to be most important, and professional nursing and physician's care were the most desired services. In nomenclature, they preferred 'elderly hospital' or 'elderly health center' to CNH. Conclusions : Interest in CNH is increasing recently, but existing studies about patient experiences in CHN are still limited. This study may form a basis for future examinations of the needs and uses for CNH. Active financial support and public information are considered by the authors to be important factors for the induction of welfare services for the elderly, though CNH.

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Artificial Insemination with Low-Dose Semen does not affect Swine Reproductive Performances

  • Chung, Ki-Hwa;Lee, Il-Joo;Sa, Soo-Jin;Kim, In-Cheul;Jung, Byeong-Yeal;Son, Jung-Ho
    • Reproductive and Developmental Biology
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    • 제37권4호
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    • pp.263-267
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    • 2013
  • Pig producers have been shown keen interest of the number of spermatozoa in a semen dose since pig artificial insemination introduce. However, determining the minimal number of spermatozoa need per AI without detrimental effect on overall reproductive performances is not an easy question to answer. To increase the efficiency of semen utilization in pig AI, optimum number of spermatozoa per dose needed to determine. The objective of this study was to determine the reproductive performance and factors that affect on-farm application of low-dose semen insemination in sows. Data were collected from Darby Genetics AI studs from 4th of June to 7th of July, 2012 (n=401). The numbers of parturition were 84, 234 and 83 in sows inseminated with doses of $1.5{\times}10^9$, $2.0{\times}10^9$ and $2.5{\times}10^9$ spermatozoa in 100ml extender, respectively. There were no significant differences on reproductive performances such as gestation period, total born, total born alive, stillbirth and mummy in sows inseminated with different semen doses. The average number of born alive was 10.5, 11.0 and 10.4 from sows inseminated with $1.5{\times}10^9$, $2.0{\times}10^9$ and $2.5{\times}10^9$ sperms, respectively. Also, number of spermatozoa per dose did not affect litter size (p>0.10). There were no significant differences of maternal genetic line difference on gestation period, total number born, number born alive, born dead and mummy. The estimated correlation coefficients of the different semen doses with total number born, number born alive, born dead and mummy were r=-0.00, -0.01, 0.02 and 0.02, respectively. Taken together, the result of this study suggested that when semen was appropriately inseminated after induced ovulation, insemination with low-dose ($1.5{\sim}2.0{\times}10^9$) semen dose not adversely affect sow's fertility.

Cyclobuxine D의 흰쥐에 있어서 ECG와 심박동수에 패한 작용과 적출 개구리 심장에 대한 작용 (Effects of Cyclobuxine D on the Electrocardiogram (ECG) and Heart Rate in Anesthetized Rats and Isolated Frog Heart)

  • 이종화;박영현;조병헌;김유재;김종배;김천숙;차영덕;김영석
    • 대한약리학회지
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    • 제22권2호
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    • pp.105-114
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    • 1986
  • 본 실험실에서는 민간요법으로 말라리아와 성병등의 치료제로 사용되어온 회양목(Buxus microphylla var. koreana Nakai)에서 steroid성 alkaloid인 cyclobuxine D와 nonalkaloid인 buxuletin을 분리하였다. Buxuletin의 가토에 있어서 이뇨작용에 대해서는 본 실험실에서 보고한바 있으며 cyclobuxine D의 약리작용에 대한 보고는 지금까지 전무한 상태이다. 본 실험에서는 새로운 항부정맥 약물의 밭견의 일환으로 cyclobuxine D의 적출 개구리 심장에 대한 작용과 마취시킨 흰쥐의 ECG와 심박동수에 대한 작용을 관찰하였다. Cyclobuxine D는 적출 개구리 심장에 대해 용량의존적 심근 수축력 감소를 나타냈으며 흰쥐에 있어서 현저한 심박동수 감소를 나타냈다. Cyclobuxine D는 흰쥐의 ECG에 있어서 PR interval과 P ${\alpha}T$ interval을 연장시키며, QRS complex와 PR interval의 심박동수에 대한 보상치인 PRc에 대해서는 고용량에서는 연장시키나 그 작용이 현저하지 않다. 이 결과로 보아 cyclobuxine D는 흰쥐의 ECG에서 A-V conduction과 ventricular depolarization에 주로 관여하는 것으로 사료 되며 이는 기존의 antiarrhythmic drugs과 비교해 볼 때 quinidine sulfate와 유사성이 있다고 추정된다.

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GABA-enriched fermented Laminaria japonica improves cognitive impairment and neuroplasticity in scopolamine- and ethanol-induced dementia model mice

  • Reid, Storm N.S.;Ryu, Je-kwang;Kim, Yunsook;Jeon, Byeong Hwan
    • Nutrition Research and Practice
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    • 제12권3호
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    • pp.199-207
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    • 2018
  • BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.

Fe-Cr-Ni-Si-C계 경면처리 합금의 Cavitation Erosion 저항성에 미치는 Vanadium 첨가의 영향 (Effect of Vanadium Addition on the Cavitation Erosion Resistance of Fe-Cr-Ni-Si-C Hardfacing Alloy)

  • 김경오;김준기;장세기;김선진;강성군
    • 한국표면공학회:학술대회논문집
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    • 한국표면공학회 1998년도 추계학술발표회 초록집
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    • pp.72-72
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    • 1998
  • 원자력발전소 1차계통내 밸브의 경면처리(hardfa따1잉에 사용되는 재료는 $90~343^{\circ}C$의 고온과 높은 접촉응력 그리고 급격한 압력변화가 일어나는 환경에서 사용되기 때문에 내마모성과 내식성 그리고 cavitation erosion 저항성이 우수한 Co계 Stellite 합금이 현재 사용되어진다. 그러나 Co가 원력발전소 1차계통의 방사선장을 형성하는 주요 원소로 알려지면서 S Stellite 합금을 대체할 수 있는 Fe계 경면처리용 합금을 개발하려는 연구가 진행되고 있다. 현재 Fe계 경면처리용 합금의 개발은 적절환 팝금원소를 첨가하여 적충결함에너지를 낮춤 으로써 전위의 교차슬립을 억제하여 표면을 경화시키고, 소성변형을 억제하여 마모저항성을 향상시키려는 방법으로 연구가 진행되고 있다. 본 연구에서는 Fe-Cr-Ni-Si-C 합금에 Fe계 합금의 적충결함에너지를 감소시키는 것으로 알려진 vanadium을 0, 1, 2wt%첨가하여 첨가량의 변화가 cavitation erosion 저항성에 미치 는 영향을 조사하였다. Cavitation erosion 실험은 초음파를 이용하여 미세한 기포를 발생시키는 vibratory type으로 A ASTM G-32 규격에 따라 제작된 실험장치를 이용하여 $25{\pm}2^{\circ}C$의 온도의 증류수 속에 잠긴 상태에서 실시하였다. 시면은 지름 16mm, 두게 7mm의 버턴형태로 vanadium 첨가량을 변화시킨 조성을 아크 용융 방법을 이용하여 제작하였으며 hom끝단부에 부착하여 cavitation e erosion 저항성 살험을 하였다. 시편의 cavitation erosion 실험시간에 따른 무게감소량을 측 정하였으며 cavitation erosion 시킨 시편의 표면을 SEM으로 관찰하였다.겨지는 열전달 매체액 과 신규 부식억제제가 적용된 시스템 등 객관적으로 확인된 부식억제제 시스랩에 대 하여 다양한 평가 방법을 동원 비교분석하고자 하였다. 실험은 KSM 2142에 의한 무게감량법, 분극곡선 측정에 의한 $E_P$(공식개시전위), $E_R$(재부동태화전위) 측정, 시간에 따른 자연전위 변화 측정 빛 이때의 부식속도(선형분극법), 인위적인 피막 파괴 전,후 의 전위 변화 및 부식속도 측정법에 의한 국부부식 발달 저지능 등을 평가하여 각 실험결과를 비교분석하여 보았다. 수록 민감하여 304 의 IGSCC 와 매우 유사한 거동을 보인다. 본 강연에서는 304 와 600 의 고온 물에서 일어나는 IGSCC 민감도에 미치는 환경, 예민화처리, 합금원소의 영향을 고찰하고 이에 대한 최근의 연구 동향과 방식 방법을 다룬다.다.의 목적과 지식)보다 미학적 경험에 주는 영향이 큰 것으로 나타났으며, 모든 사람들에게 비슷한 미학적 경험을 발생시키는 것 이 밝혀졌다. 다시 말하면 모든 사람들은 그들의 문화적인 국적과 사회적 인 직업의 차이, 목적의 차이, 또한 환경의 의미의 차이에 상관없이 아름다 운 경관(High-beauty landscape)을 주거지나 나들이 장소로서 선호했으며, 아름답다고 평가했다. 반면에, 사람들이 갖고 있는 문화의 차이, 직업의 차 이, 목적의 차이, 그리고 환경의 의미의 차이에 따라 경관의 미학적 평가가 달라진 것으로 나타났다.corner$적 의도에 의한 경관구성의 일면을 확인할수 있지만 엄밀히 생각하여 보면 이러한 예의 경우도 최락의 총체적인 외형은 마찬가지로 $\ulcorner$순응$\lrcorner$의 범위를 벗어나지 않는다. 그렇기 때문에도 $\ulcorner$

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안와골절 정복술에 사용된 인공삽입물의 전산화단층촬영 추적관찰 (CT Observation of Alloplastic Materials Used in Blow Out Fracture)

  • 이원;강동희
    • Archives of Plastic Surgery
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    • 제37권4호
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    • pp.380-384
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    • 2010
  • Purpose: Distinguishing different types of implants and assessing the position and size of implants by radiologic exam after orbital wall reconstruction is important in determining the surgery outcome and forecasting prognosis. We observed time-dependent density changes in three types of implants (porous polyethylene, resorbing plate and titanium mesh plate) by performing facial bone CT after orbital wall reconstructions. Methods: A total of 32 patients, who had underwent orbital wall fracture surgery from October 2006 to March 2009 and received facial bone CT as outpatients at 1 postoperative year were included in the study. Follow-up facial bone CT was performed on the patients pre- operatively, 1 month post-operatively, and 1 year post-operatively to observe the status of the orbital implants. Medpor $^{(R)}$ (Porex Surgical, Inc., Newnan, Ga.) was used as porous polyethylene and followed-up in 14 cases; for resorbing plate, Synthes mesh plate (Synthes, Oberdorf, Switzerland) was used in the reconstruction, and followed-up in 11 cases; and titanium mesh plate usage was followed-up in 7 cases. Computed tomographic scan (CT) and water's view were done for radiography, and hounsfield unit (HU) was used to compare density of those facial bone CT. Wilcoxon signed rank test was applied to statistically verify measurement difference in each group of hounsfield units. Results: Facial bone CT examination performed in 1 month post-operative showed that the density of porous polyethylene, resorbing plate and titanium mesh plate were -42.07, 105.67 and 539.48 on average, respectively. Among the three types of implants, titanium mesh plate showed the highest density due to its radiopaque feature. Following up the density of three types of implants in CT during 1 year after the orbital wall fracture surgery, the density of porous polyethylene increased in 10.52 House Field Units and the resorbing plate was decreased in 26.87 HouseField Units. There were no significant differences between densities in 1 month post-operatively and 1 year post-operatively in each group ($p{\geq}0.05$). Conclusion: We performed facial bone CT on patients with orbital fractures during follow-up period, distinguishing the types of implants by the different concentration of implant density, and the densities showed little change even at 1 year post-operative. To observe how implant densities change in facial bone CT, further studies with longer follow-up periods should be carried out.

Improved Socio-Economic Status of a Community Population Following Schistosomiasis and Intestinal Worm Control Interventions on Kome Island, North-Western Tanzania

  • Mwanga, Joseph R.;Kaatano, Godfrey M.;Siza, Julius E.;Chang, Su Young;Ko, Yunsuk;Kullaya, Cyril M.;Nsabo, Jackson;Eom, Keeseon S.;Yong, Tai-Soon;Chai, Jong-Yil;Min, Duk-Young;Rim, Han-Jong;Changalucha, John M.
    • Parasites, Hosts and Diseases
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    • 제53권5호
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    • pp.553-559
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    • 2015
  • Research on micro-level assessment of the changes of socio-economic status following health interventions is very scarce. The use of household asset data to determine wealth indices is a common procedure for estimating socio-economic position in resource poor settings. In such settings information about income is usually lacking, and the collection of individual consumption or expenditure data would require in-depth interviews, posing a considerable risk of bias. In this study, we determined the socio-economic status of 213 households in a community population in an island in the north-western Tanzania before and 3 year after implementation of a participatory hygiene and sanitation transformation (PHAST) intervention to control schistosomiasis and intestinal worm infections. We constructed a household 'wealth index' based housing construction features (e.g., type of roof, walls, and floor) and durable assets ownership (e.g., bicycle, radio, etc.). We employed principal components analysis and classified households into wealth quintiles. The study revealed that asset variables with positive factor scores were associated with higher socio-economic status, whereas asset variables with negative factor scores were associated with lower socio-economic status. Overall, households which were rated as the poorest and very poor were on the decrease, whereas those rated as poor, less poor, and the least poor were on the increase after PHAST intervention. This decrease/increase was significant. The median shifted from -0.4376677 to 0.5001073, and the mean from -0.2605787 (SD; 2.005688) to 0.2605787 (SD; 1.831199). The difference in socio-economic status of the people between the 2 phases was highly statistically significant (P<0.001). We argue that finding of this study should be treated with caution as there were other interventions to control schistosomiasis and intestinal worm infections which were running concurrently on Kome Island apart from PHAST intervention.

간섬유화 동물에서 옻나무 목부로부터 분리한 flavonoids의 독성 경감기전 (Protective Mechanism of Flavonoids Isolated from Rhus verniciflua on the Biliary Liver Fibrosis in Rat)

  • 최종원;박희준;이경태;박건영;한갑이;정민화
    • 생명과학회지
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    • 제12권3호
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    • pp.332-339
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    • 2002
  • 옻나무(Rhus verniciflua Stokes)로부터 간섬유화에 따른 간독성의 경감기전을 추구할 목적으로 ethyl acetate 분획에서 분리한 fustin 및 sulfuretin을 실험동물에 투여하고서 혈액학적 변화 및 간장 중 활성산소에 미치는 영향 검토한 결과 담도결찰하여 간섬유화를 유도한 군에서는 AST, ALT, SDH, ${\gamma}$-GT활성 및 total bilirubin의 양이 현저히 증가되던 것이 옻나무의 메탄을 엑스(250 mg/kg), 에틸아세테이트 엑스(250 mg/kg), fustin(10 mg/kg) 및 sulfuretin(10 mg/kg)을 2주간 각각 경구투여 하므로서 유의성 있게 억제되었다. Hydroxyproline양 및 MDA 농도에서도 간섬유화를 유도하므로서 현저히 증가되던 것이 옻나무의 분획 및 sulfuretin과 fustin의 투여로서 각각 약 60% 및 47%정도 감소되었다. 간섬유화를 유도한 cytosolic계 효소인 xanthine oxidase 및 aldehyde oxidase의 활성이 현저히 증가되었으며 한편 superoxide dismutase, glutathione peroxidase 및 catalase은 간섬유화의 유도로 감소되었으나 옻나무의 분획(메탄올, 에틸아세테이트) 및 성분(fustin, sulfuretin)의 투여로서 조절되었다.