• Title/Summary/Keyword: CYP model

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Effectiveness Analysis on Comb Pen Shell Based on TAC System (키조개 TAC 제도의 효과 분석)

  • Jeong, Min-Ju;Nam, Jong-Oh
    • The Journal of Fisheries Business Administration
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    • v.47 no.3
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    • pp.15-33
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    • 2016
  • This study aims to analyze effectiveness of the resource use under the total allowable catch system (TACs) of Comb pen shell, a species among TAC targeting ones through its stock assessment based on the surplus production model such as the Clark Yoshimoto Pooley (CYP) model. Particularly, this study is separated into five analysis periods in order to understand changes in Comb pen shell resource and its efficient use after TAC system implemented in 2001. The results of this study are as follows. First, five sustainable yield curves (SYCs) and exponential growth functions (EGFs) produced by the surplus production model based on Gompertz growth function to compare before and after implementation of the Korean TAC system show that the TAC system has generated a positive stock rebuilding effect for Comb pen shell caught by the diver fishery since 2001. Secondly, five profits based on differences between the sustainable total revenue (STR) and the total cost (TC) with respect to fishing efforts present that the TAC system has increased efficiency of resource use of Comb pen shell caught by the diver fishery after implementation of the Korean TAC system. In conclusion, the Korean TAC system has increased efficiency of resource use as well as has led a positive stock rebuilding effect for Comb pen shell.

The effects of the standardized extracts of Ginkgo biloba on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells

  • Kim, Mijie;Park, Yong Joo;Ahn, Huiyeon;Moon, Byeonghak;Chung, Kyu Hyuck;Oh, Seung Min
    • Environmental Analysis Health and Toxicology
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    • v.31
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    • pp.10.1-10.8
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    • 2016
  • Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and $17{\beta}$-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases ($3{\beta}$-HSD2 and $17{\beta}$-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and $100{\mu}g/mL$) showed a significant decrease in $17{\beta}$-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and $17{\beta}$-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and $17{\beta}$-HSD1, and lead to a decrease in $17{\beta}$-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

The Design and Fabrication of μCCA-μGI Device for Toxicity Evaluation of Acetaminophen (아세트아미노펜 독성평가를 위한 μCCA-μGI 디바이스의 개발)

  • Chang Jung-Yun;Shuler Michael L.
    • Journal of Pharmaceutical Investigation
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    • v.36 no.4
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    • pp.263-269
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    • 2006
  • Deficiencies in the early ADMET(absorption, distribution, metabolism, elimination and toxicity) information on drug candidate extract a significant economic penalty on pharmaceutical firms. Microscale cell culture analogue-microscale gastrointestinal(${\mu}CCA-{\mu}GI$) device using Caco 2, L2 and HEp G2/C3A cells, which mimic metabolic process after absorption occurring in humans was used to investigate the toxicity of the model chemical, acetaminophen(AAP). The toxicity of acetaminophen determined after induction of CYP 1A1/2 in Caco 2 cells was not significant. In a coculture system, although no significant reduction in viability of HEp G2/C3A and L2 cells was found, approximately 5 fold increase in the CYP 1A1/2 activity was observed. These results appear to be related to organ-organ interaction. The oral administration of a drug requires addition of the absorption process through small intestine to the current ${\mu}CCA$ device. Therefore, a perfusion coculture system was employed for the evaluation of the absolution across the small intestine and resulting toxicity in the liver and lung. This system give comprehensive and physiologic information on oral uptake and resulting toxicity as in the body. The current ${\mu}CCA$ device can be used to demonstrate the toxic effect due to organ to organ interaction after oral administration,

Genotoxic Effects of Diesel Exhaust Particle Extract in NIH/3T3 Cells (디젤분진이 체세포에서의 DNA 손상에 미치는 영향)

  • Heo Chan;Kim Nam Yee;Chung Kyu-Hyuek;Moon Chang-Kiu;Heo Moon Young
    • Environmental Analysis Health and Toxicology
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    • v.19 no.4
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    • pp.335-344
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    • 2004
  • Diesel exhaust particle (<2.5 ${\mu}{\textrm}{m}$, DEP$_{2.5}$) is known to be probarbly carcinogenic (IARC group 2A). DEP$_{2.5}$ contains organic compounds such as polycyclicaromatic hydrocarbon (PAH), heterocyclic compounds, phenols, and nitroarenes. Reactive oxygen species (ROS) are generated by DEP$_{2.5}$ without any biological activation system. Therefore, an alternative mechanism by which DEP$_{2.5}$ could be carcinogenic is known by the generation of oxidative DNA damage. The aim of this study was to investigate genotoxic effects of DEP$_{2.5}$ using single cell gel electrophoresis. In order to evaluate the mechanisms of DEP$_{2.5}$ genotoxicity, the rat micro-some mediated and DNA repair enzyme treated comet assays together with routine comet assay were performed. DEP$_{2.5}$ was collected from diesel engine bus and dichloromethane extract was obtained. The organic extract of DEP$_{2.5}$ revealed DNA damage itself in NIH/3T3 cells. And it showed both oxidative and microsome mediated DNA damages. Vitamin C as an model antioxidant reduced DNA damage in endonuclase III treated comet assay. One of flavonoid, galangin as a CYP1A1 inhibitor reduced DNA damage in the presence of S-9 mixture. Our results show that DEP$_{2.5}$ are genotoxic and a great source of oxidative stress, but antioxidants can significantly reduce oxidative DNA damages. And DEP$_{2.5}$ may contain indirect mutagens which can be inhibited by CYP inhibitors.d by CYP inhibitors.

The Effect of Dehydronifedipine on the Oxidation of Aflatoxin $B_1$ by Cytochrome P450 3A4 (Cytochrome P450 3A4에 의한 Aflatoxin $B_1$의 산화에 대한 Dehydronifedipine의 영향)

  • 김복량;권강범;김동현
    • Toxicological Research
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    • v.15 no.1
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    • pp.95-101
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    • 1999
  • Cytochrome P450 (CYP) 3A4 metabolizes aflatoxin B1 (AFB1) to AFB1-exo-8,9-epoxide (8,9-epoxidation) and aflatoxin Q1 (AFQ1; 3$\alpha$-hydroxylation) simultaneously. We investigated whether each metabolite was formed via its own binding site of CAP3A4 active site. Kinetics of the formation of the two metabolites were sigmoidal and consistent with the kinetics of substrate activation. The HIll model predicted that two substrate binding wites are involved in the oxidationof AFB1 by CYP3A4. Dehydronifedipine, a metabolite of nifedipine generated by CYP3A4, inhibited the formation of AFQ1 without any inhibition in the formation of AFB1-exo-8,9-epoxidation. Dehydronifedipine was found to act as a reversible competitive inhibitor against 3$\alpha$-hydroxylation of AFB1. Vmax and S0.5 of the 8,9-epoxidation were not changed in the presence of 0, 50, or 100 $\mu\textrm{M}$ dehydronifedipine. S0.5 of 3$\alpha$-hydroxylation was increased from 58$\pm$4 $\mu\textrm{M}$ to 111$\pm$8 $\mu\textrm{M}$ in the presence of 100 $\mu\textrm{M}$ nifedipine whereas Vmax was not changed. These results suggest that there exist two independent binding sites in the active site of CAP3A4 . One binding site is responsible for AFB1-exo-8,9-epoxidation and the other is involved in 3$\alpha$-hydroxylation of AFB1. Dehydronifedipine might selectively bind to the site which is responsible for the formation of AFQ1 in the active site of CYP3A4.

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Functional RsaI/PstI Polymorphism in Cytochrome P450 2E1 Contributes to Bladder Cancer Susceptibility: Evidence from a Meta-analysis

  • Deng, Xiao-Dong;Gao, Qin;Zhang, Bo;Zhang, Li-Xia;Zhang, Wei;Er, Zhe-Er Mu;Xie, Ying;Ma, Ying;Liu, Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4977-4982
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    • 2014
  • Background: Cytochrome P450 2E1 (CYP2E1) might be involved in the development of bladder cancer. However, previous studies of any association between CYP2E1 RsaI/PstI polymorphism and bladder cancer risk have yielded conflicting results. In this study, we performed a more precise estimation of the relationship by a meta-analysis based on the currently available evidence from the literature. Method: To assess the effect of CYP2E1 RsaI/PstI polymorphism on bladder cancer susceptibility, a meta-analysis of 6 available studies with 1,510 cases and 1,560 controls were performed through Feb 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of association for CYP2E1 RsaI/PstI polymorphism under different genetic models. Results: When available studies were pooled into the meta-analysis, we found that the C1C2 and C2C2 genotypes of CYP2E1 RsaI/PstI polymorphism significantly decreased bladder cancer risk under different genetic models (heterozygote: OR=0.766, 95%CI=0.613-0.957, $P_{OR}$=0.019; homozygote: OR=0.51, 95%CI=0.303-0.858, $P_{OR}$=0.011; dominant: OR=0.733, 95%CI=0.593-0.905, $P_{OR}$=0.004; recessive: OR=0.565, 95%CI=0.337-0.947, $P_{OR}$=0.030). Subgroup analysis indicated that C2C2 genotype was significantly associated with decreased bladder cancer risk under the homozygote genetic model in Caucasians. There was no evidence of heterogeneity or publication bias. Conclusions: The current meta-analysis suggested that the CYP2E1 RsaI/PstI polymorphism might be associated with bladder cancer susceptibility, especially in Caucasians. Further studies are needed to validate the above conclusion.

A study on the estimation of potential yield for Korean west coast fisheries using the holistic production method (HPM) (통합생산량분석법에 의한 한국 서해 어획대상 잠재생산량 추정 연구)

  • KIM, Hyun-A;SEO, Yong-Il;CHA, Hyung Kee;KANG, Hee-Joong;ZHANG, Chang-Ik
    • Journal of the Korean Society of Fisheries and Ocean Technology
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    • v.54 no.1
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    • pp.38-53
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    • 2018
  • The purpose of this study is to estimate potential yield (PY) for Korean west coast fisheries using the holistic production method (HPM). HPM involves the use of surplus production models to apply input data of catch and standardized fishing efforts. HPM compared the estimated parameters of the surplus production from four different models: the Fox model, CYP model, ASPIC model, and maximum entropy model. The PY estimates ranged from 174,232 metric tons (mt) using the CYP model to 238,088 mt using the maximum entropy model. The highest coefficient of determination ($R^2$), the lowest root mean square error (RMSE), and the lowest Theil's U statistic (U) for Korean west coast fisheries were obtained from the maximum entropy model. The maximum entropy model showed relatively better fits of data, indicating that the maximum entropy model is statistically more stable and accurate than other models. The estimate from the maximum entropy model is regarded as a more reasonable estimate of PY. The quality of input data should be improved for the future study of PY to obtain more reliable estimates.

Alcohol Induced Hepatic Fibrosis in Pig

  • Lee, Chang-Woo;Lee, Cha-Soo;Jeong, Won-Il;Do, Sun-Hee;Noh, Dong-Hyung;Jeong, Kyu-Shik
    • Proceedings of the Korean Society of Veterinary Pathology Conference
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    • 2002.11a
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    • pp.146-146
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    • 2002
  • Hepatic disease has been noted and reported for involvement various detrimental factors. Among many detrimental injury factors, alcohol has been noted for hepatitis, fatty liver, fibrosis, and hepatic cirrhosis. The purpose of this study is to develop animal model for hepatic fibrosis in pig with ethanol, and to search new anti-fibrogenic agent. Twelve male Landrace pigs were divided into 3 groups of 4 animals each. Group 1, 2 and 3 were fed with ceramic water only, ceramic water + liquid diet containing 20% ethanol and normal tap water + containing 20% ethanol for 12 weeks, respectively. At week 12, all pigs were immediately sacrificed for collection each tissue and blood. Serologically, serum ALT and AST levels were significantly reversed in group 2, comparing to group 3. They were normal range in pigs of group 1. Microscopically, macrovesicular lipid droplets and moderate necrosis were evident in the tap water + ethanol fed group 3. However, ceramic water intake group 1 showed normal. Moreover, in group 3, little fatty changes and mild necrosis were observed. Collagen fibers were detected in the spaces of surrounding periportal and interlobular areas in the group 3 of tap water + ethanol, but collagen synthesis and its thickness of fibrotic septa connecting portal tracts was markedly reduced in the group 2 of ceramic water + ethanol. In immunohistochemistry, myofibroblasts were detected in the ethanol and tap water treated group 3. No or a few myofibroblasts were observed in groups 1 and 2. CYP 2E1 was rarely detected in group 1 fed ceramic water. However, group 2 showed slightly activation of CYP 2E1 in the area of pericentral, while CYP 2E1 was significantly activated in group 3 fed tap and ethanol. Taken together above, alcohol fibrosis model in pig was established. Furthermore, ceramic water had an inhibitory and protecting ability for alcohol-induced hepatic damages.

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Climatic Yield Potential Changes Under Climate Change over Korean Peninsula Using 1-km High Resolution SSP-RCP Scenarios (고해상도(1km) SSP-RCP시나리오 기반 한반도의 벼 기후생산력지수 변화 전망)

  • Sera Jo;Yong-Seok Kim;Jina Hur;Joonlee Lee;Eung-Sup Kim;Kyo-Moon Shim;Mingu Kang
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.25 no.4
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    • pp.284-301
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    • 2023
  • The changes in rice climatic yield potential (CYP) across the Korean Peninsula are evaluated based on the new climate change scenario produced by the National Institute of Agricultural Sciences with 18 ensemble members at 1 km resolution under a Shared Socioeconomic Pathway (SSP) and Representative Concentration Pathways (RCP) emission scenarios. To overcome the data availability, we utilize solar radiation f or CYP instead of sunshine duration which is relatively uncommon in the climate prediction f ield. The result show that maximum CYP(CYPmax) decreased, and the optimal heading date is progressively delayed under warmer temperature conditions compared to the current climate. This trend is particularly pronounced in the SSP5-85 scenario, indicating faster warming, except for the northeastern mountainous regions of North Korea. This shows the benef its of lower emission scenarios and pursuing more efforts to limit greenhouse gas emissions. On the other hand, the CYPmax shows a wide range of feasible futures, which shows inherent uncertainties in f uture climate projections and the risks when analyzing a single model or a small number of model results, highlighting the importance of the ensemble approach. The f indings of this study on changes in rice productivity and uncertainties in temperature and solar radiation during the 21st century, based on climate change scenarios, hold value as f undamental information for climate change adaptation efforts.

Chemopreventive Effect of Vegetable or Fruit Extract Against Total Diesel Exhaust Particle Extract in NIH/3T3 Cells Using Alkaline Single Cell Gel Electrophoresis (총 디젤분진의 DNA 손상작용과 야채 및 과일추출물의 보호효과)

  • Heo Chan;Kim Nam-Yee;Heo Moon-Young
    • Environmental Analysis Health and Toxicology
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    • v.21 no.2 s.53
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    • pp.127-138
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    • 2006
  • In urban areas, diesel exhaust particles (DEP) are probably a major component of particulate matters, especially in Korea where drive many diesel vehicles. The aim of this study was to investigate genotoxic effects of DEP using single ceil gel electrophoresis. In order to evaluate the mechanisms of DEP genotoxicity, the rat microsome mediated and DNA repair enzyme treated comet assays together with conventional comet assay were performed. Total diesel particles (DEPT) was collected without site fractionation from diesel engine bus and dichloromethane extract was obtained. The organic extract of DEPT revealed DNA damage itself in NIH/3T3 cells. The level of DNA breaks plus oxidative DNA lesions and microsome mediated DNA damage was assessed by modified single cell gel eletrophoresis. DEPT was able to induce oxidative DNA damage as well as microsome mediated DNA damage. Vitamin C as an model antioxidant reduced DNA damage in endonuclase III treated comet assay. One of flavonoid, galangin as a CYP1A1 inhibitor. reduced DNA damage in the presence of S-9 mixture. $DEP_T$ is the sources of oxidative stress, but antioxidants can significantly reduce oxidative DNA dmage. And $DEP_T$ may contain indirect mutagens which can be inhibited by CYP1A1 inhibitors. The ethanol extracts of the mixed vegetables (BV) or the mixed fruits (BF) were evaluated for their in vitro antigenotoxic effects. BV and BF showed potent Inhibitory effects against DEPT induced DNA damage with oxidative DNA lesions and in the prescence of S-9 mixture. These results indicate that BV and BF could prevent cellular DNA damage by inhibiting oxidative stress and suppressing cytochrome P4501A1 in cell culture.