• Title/Summary/Keyword: Damage rates

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Oxyradical Formation during the Hepatocarcinogenesis in Rat (흰쥐 간발암화 과정에서의 산소유리기의 동태)

  • Kim, Hyoung-Chun;Chun, Wan-Jhoo;Lee, Hyun-Woo;Kwon, Myung-Sang;Song, Kye-Yong;Jhoo, Wang-Kee
    • YAKHAK HOEJI
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    • v.36 no.2
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    • pp.180-187
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    • 1992
  • This study investigated the hypothesis that carcinogen-induced elevation of oxyradical during the hepatocarcinogenesis in rat. The hepatic preneoplastic lesions in the Spraque-Dawley rats were induced by the carcinogen treatment such as diethylnitrosamine(DEN) and acetylaminofluorene(AAF) in combination with partial hepatectomy(PH). The liver sample was taken at 2, 6, 10 and 16 months after carcinogen treatments followed by PH. Carcinogen treatments initially increased the indices of oxidative damage(activities of xanthine oxidase and production rates of superoxide anion, microsomal hydrogen peroxide, hydroxyl radical) in the liver compared to PH groups. However, cytosolic hydrogen peroxide did not change significantly throughout the full time period. Of hydrogen peroxide scavenger, the catalase was remained lower than PH groups, whereas the peroxidase was increased after carcinogen treatments. Morphologically, the immunohistochemical analysis with glutathione-S-transferase of a placenta form(GSTP) antibody was used to detect the induction of preneoplastic nodules. During the hepatocarcinogenesis, both production rate of hydroxyl radical and activity of glutathione-S-transferase(GST) markedly increased with the appearance of the preneoplastic nodule. These results indicated that the hydroxyl radical of reactive oxygen species seemed to have a major influence on the hepatocarcinogenesis and the effect of time after removal of the carcinogen also appeared to be highly critical in the hepatocarcinogenesis.

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In Vitro Metabolism of a New Neuroprotective Agent, KR-31543 in the Human Liver Microsomes : Identification of Human Cytochrome P450

  • Ji, Hye-Young;Lee, Seung-Seok;Yoo, Sung-Eun;Kim, Hosoon;Lee, Dong-Ha;Lim, Hong;Lee, Hye-Suk
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.239-245
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    • 2004
  • KR-31543, (2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2 -methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran, is a new neuroprotective agent for preventing ischemia-reperfusion damage. This study was performed to identify the metabolic pathway of KR-31543 in human liver microsomes and to characterize cytochrome P450 (CYP) enzymes that are involved in the metabolism of KR-31543. Human liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of two metabolites, M1 and M2. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC/MS/MS analysis with a synthesized authentic standard, and M2 was suggested to be hydroxy-KR-31543. Correlation analysis between the known CYP enzyme activities and the rates of the formation of M 1 and M2 in the 12 human liver microsomes have showed significant correlations with testosterone 6$\beta$-hydroxylase activity (a marker of CYP3A4). Ketoconazole, a selective inhibitor of CYP3A4, and anti-CYP3A4 monoclonal antibodies potently inhibited both N-hydrolysis and hydroxylation of KR-31543 in human liver microsomes. These results provide evidence that CYP3A4 is the major isozyme responsible for the metabolism of KR-31543 to M1 and M2.

Beneficial Effect of Taeumjowi-tang on the Cisplatin-Induced Gastrointestinal Dysfunctions in Rats (시스플라틴으로 유발된 랫트의 위장관 운동장애에 대한 태음조위탕의 효과)

  • Kim, Seong-Tae;Choi, Ae-Ryun
    • Journal of Sasang Constitutional Medicine
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    • v.27 no.2
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    • pp.254-269
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    • 2015
  • Objectives This study aimed to observe the effect of Taeumjowi-tang on the cisplatin-induced gastrointestinal dysfunctions in rats. Methods Four groups, each of 8 rats per group, were used in this study. Saline and distilled water treated control rats were intact vehicle control group. Delayed gastrointestinal motility was induced by intraperitoneal treatment of cisplatin 2mg/kg, once a week for 5 weeks(Cisplatin control group). Taeumjowi-tang aqueous extracts(TJ) were orally administered in a volume of 5ml/kg, once a day for 14 days from 4th cisplatin treatment(TJ group). Ondansetron 1mg/kg was subcutaneously treated, in a volume of 1ml/kg, as same as TJ(ondansetron group). We measured the body weights, intestinal charcoal transit ratio, fecal parameters, fundus MDA(malondialdehyde), GSH(glutathione) contents and SOD(superoxide dismutase), CAT(catalase) activities, TPH(tryptophanhydroxylase) and MAO(monoamine oxidase) activities, pyloric gastrin and serotonin contents with their immunoreactive cells, colonic serotonin-immunoreactive cells, the histopathology of pylorus, fundus mucosa and colon. Results 1) The body weight gains, the small intestinal charcoal transfer rates, the fecal parameters(numbers, weights and water contents) were increased in TJ, ondansetron group. 2) The inhibit of fundus antioxidant defense systems by cisplatin were decreased in TJ, ondansetron group. 3) The pyloric TPH activities were increased and the pyloric MAO activities were decreased in TJ group. 4) The pyloric gastric contents and the gastrin-immunoreactive cells were increased and the pyloric serotonin contents and the pyloric and colonic serotonin-immunoreactive cells were decreased in TJ group. 5) The pylorus atrophic changes and the gastric surface erosive damage regions by cisplatin were favorably inhibited by treatment of TJ group. Conclusions The results obtained in this study suggest that TJ favorably retarded the cisplatin related GI(gastrointestinal) dysfunctions and constipation through modulations of GI enterochromaffin cells, serotonin and gastrin-producing cells and antioxidative systems.

Oxymatrine Causes Hepatotoxicity by Promoting the Phosphorylation of JNK and Induction of Endoplasmic Reticulum Stress Mediated by ROS in LO2 Cells

  • Gu, Li-li;Shen, Zhe-lun;Li, Yang-Lei;Bao, Yi-Qi;Lu, Hong
    • Molecules and Cells
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    • v.41 no.5
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    • pp.401-412
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    • 2018
  • Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

Analysis of Scattering Rays and Shielding Efficiency through Lead Shielding for 0.511 MeV Gamma Rays Based on Skin Dose (피부선량을 기준으로 0.511 MeV 감마선에 대한 납 차폐체의 산란선 및 차폐 효율 분석)

  • Jang, Dong-Gun;Park, Eun-Tae
    • Journal of radiological science and technology
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    • v.43 no.4
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    • pp.259-264
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    • 2020
  • Radiation causes radiation hazards in the human body. In Korea, a case of radiation necrosis occurred in 2014. In this study, the scatter and shielding efficiency according to lead shielding were classified into epidermis and dermis for 0.511 MeV used in nuclear medicine. In this study, experiments were conducted using the slab phantom that represents calibration and the dose of human trunk. Experimental results showed that the shielding rate of 0.25 mmPb was 180% in the epidermis and 96% in the dermis. Shielding at 0.5mmPb showed shielding rates of 158%in the epidermis and 82% in the dermis. As a result of measuring the absorbed dose by subdividing the thickness of the dermis into 0.5 mm intervals, when the shielding was carried out at 0.25 mmPb, the dose appeared to be about 120% at 0.5 mm of the dermis surface, and the dose was decreased at the subsequent depth. Shielding at 0.5 mmPb, the dose appeared to be about 101% at the surface 0.5 mm, and the dose was measured to decrease at the subsequent depth. This result suggests that when lead aprons are actually used, the scattering rays would be sufficiently removed due to the spaces generated by the clothes and air, Therefore, the scattered ray generated from lead will not reach the human body. The ICRU defines the epidermis (0.07), in which the radiation-induced damage of the skin occurs, as the dose equivalent. If the radiation dose of the dermis is considered in addition, it will be helpful for the evaluation of the prognosis for radiation hazard of the skin.

Effects of an Ethylacetate Fraction of Chrysanthemi Flos on the Antioxidative System and Lipid Profile in Rats with Ethanol-Induced Liver Damage

  • Choo, Myung-Hee;Jeong, Yoon-Hwa;Lee, Myung-Yul
    • Preventive Nutrition and Food Science
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    • v.9 no.4
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    • pp.352-360
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    • 2004
  • To investigate the antioxidative effects of an etbylacetate fraction extracted from the flowers of Chrysanthemum indicum L. (Chrysanthemi Flos) on the antioxidative system and lipid profiles of rats with ethanol induced hepatotoxicity. Sprague-Dawley rats weighing $100\~150$ g were divided into 5 groups: normal group (NOR), Chrysanthemi Flos EtOAC fraction (200 mg/kg) treated group (S1), $35\%$ etbanol (10 mL/kg) treated group (S2), Chrysanthemi Flos EtOAC fraction (200 mg/kg) and ethanol concomitantly treated group (S3) and Chrysanthemi Flos EtOAC fraction (400 mg/kg) and ethanol concomitantly treated group (S4), respectively. The antioxidative activity of each fraction was decreased in order of EtOAC, n-hexane, n-BuOH, water and chloroform. The growth rates and feed efficiency ratios were decreased by ethanol treatment, but were gradually restored to similar levels as in the NOR group by administering Chrysanthemi Flos EtOAC fraction. The whole blood concentrations of total cholesterol and LDL-cholesterol, and the activities of ALT and AST that were elevated by ethanol were significantly decreased in the Chrysanthemi Flos EtOAC fraction treated groups. It was also observed that the activities of SOD, catalase, xanthine oxidase and GSH-Px elevated by ethanol in rat liver were markedly decreased in the Chrysanthemi Flos EtOAC fraction treated group as compared to S2. These results suggest that Chrysanthemi Flos EtOAC fraction has possible protective effects against ethanol induced hepatotoxicity in rat liver.

Protective Effects and Anti-oxidative Effects of Sipjeon-Daebo-Tang and Gami-Sipjeon-Daebo-Tang in C6 Glioma Cell (십전대보탕(十全大補湯) 및 가미십전대보탕(加味十全大補湯)의 항산화 효과 및 신경교세포주 보호 효과)

  • Lee, Sang-Yeong;Kim, Hyung-Woo;Kim, Gye-Yep;Choi, Chan-Hun;Yun, Yeo-Chung;Jeong, Hyun-Woo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.6
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    • pp.1292-1298
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    • 2009
  • Sipjeon-Daebo-Tang (SDT) is indicated for deficiency syndrome of both gi and blood, marked by pale or sallow complexion, dizziness, lassitude, shortness of breath, dislike for talking, poor appetite, pale tongue with thin whitish fur, thready and weak pulse. Gami-Sipjeon-Daebo-Tang(GSDT) is composed of 10 herbs within SDT and Cervi Pantotrichum Cornu (CPC). CPC can noursh kidney-yang, promote the production of the essence and blood, strengthen tendons and bones. Recently SDT is known as anti-cancer drug. Especially CPC is reported to have anti-oxidative action. For these reasons, we investigated the protective effects on cell death induced by chemicals such as paraquat, hydrogen peroxide and anti-oxidative effects in C6 glioma cells. In our results, GSDT accelerated proliferation rates of C6 cells in vitro. In addition, protective effects on cell death induced by hydrogen peroxide and rotenone. In addition, SOD activities were increased by treatment with both SDT and GSDT. In conclusion, these results suggest the possibility of GSDT to protect brain cell or neuronal cell from damage induced by oxidative stress. And also suggest that related mechanisms are involved in SOD activities.

A Study on the Development and of Establishment Performance Evaluation Criteria of Working Truck Mounted Attenuator (작업차량 장착용 충격흡수장치(TMA) 성능평가기준 수립 및 개발 연구)

  • Joo, Jae-Woong;Jang, Dae-Young;Park, Je-Jin
    • Journal of the Korean Society of Safety
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    • v.27 no.6
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    • pp.185-191
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    • 2012
  • Rear collisions to expressway work trucks result many casualties these days. But, currently, no special measure are being taken except deploying sign trucks behind the working trucks. In the U.S and Europe, trucks with TMA(Truck Mounted Attenuator) are being deployed behind the working truck, which is regarded as the standard method for work area safety, thereby reducing the fatality rates and property damage tremendously. Also, standard for the performance of TMA are established and TMA can be used in the field only when it satisfies the standard. In Korea, neither the standard for nor any guide to the TMA exists. In the situation some manufacturer developed TMA without proper performance evaluation and marketed limited number of TMAs in the field. In the study, NCHRP350, which is the performance standard of expressway safety features of U.S. and materials related to the TMA standard in Europe have been reviewed to establish the Korean performance criteria. Based on the review, and incorporating existing Korean standard for crash cushions, domestic standard for TMA has been proposed and applied in developing Korean TMA and crash tested it to verify the performance. The original design developed was crash tested and modified. The newly proposed design was studied using impact simulation program several times. Modifications were made after each simulation and prototype was built and crash tested as per the newly established TMA performance criteria.

A Monitoring and Data Analysis for Close-to-Nature Pilot Creeks (자연형 소하천 모니터링 시범사업 결과 분석)

  • Yi, Sang-Kuk;Chung, Jae-Hak;Lee, Ho-Yul;Lee, Jong-Seol
    • 한국방재학회:학술대회논문집
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    • 2008.02a
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    • pp.751-754
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    • 2008
  • Recently according to increasing of damage in creeks, it has been needed to develop a close-to-nature creek improvement technique considering flood safety as well as the functions of ecosystem and scenery preservation. In this study, the monitoring on creeks in seven provinces was accomplished to develop the technique applicable to domestic creeks between 2002 and 2007. Although the riparian ecosystem was disturbed, after just finishing the improvement on pilot creeks, the result of monitoring showed that restoration rates of creeks were satisfactory by constructing close-to-nature creek revetments. However it is hard to analyze on restoration and permissible tractive force of each revetments constructed in most creeks, because of insufficient monitoring data. Therefore the feasible study on the close-to-nature creek revetments should be performed in the near future through continuous monitoring on creeks.

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Risk Reduction Rate for Each Risk Mitigation Measure on High Pressure Urban Gas Pipelines Proposed by Quantitative Risk Analysis (정량적 위험성 평가를 통해 제안된 도시가스 고압배관의 위험경감조치별 위험감소효과)

  • Ryou, Young-Don;Jo, Young-Do;Park, Young-Gil;Lee, Su-Kyung
    • Journal of the Korean Institute of Gas
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    • v.14 no.4
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    • pp.18-23
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    • 2010
  • After conducting QRA(quantitative risk assessment) for the high pressure urban gas pipelines planned to be installed, RMMs(risk mitigation measures) when the societal risk is outside the acceptable region have been derived in this paper. Also risk reduction rates are calculated for each RMM. As a result of QRA, we find out that damaged distance caused by radiational heat is largely dependent upon the wind velocity and the atmospheric stability. The measure that has the highest risk reduction effect is No. 10 which includes pipeline corrosion monitoring, MOV(motor operated valve) installation and the method to protect pipeline damage caused by third-party mechanical interference, and which shows 75 % of risk reduction effect.