• Title/Summary/Keyword: MFO

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Responses in Hepatic Xenobiotic Metabolizing and Antioxidant Enzymes in Javelin Goby Acanthogobius hasta Collected at Shihwa Lake (시화호에서 채집한 풀망둑 Acanthogobius hasta의 간장 약물대사효소계 및 항산화계의 반응)

  • Lee, Ji-Seon;Jeong, Jee-Hyun;Han, Chang-Hee;Shim, Won-Joon;Jeon, Joong-Kyun
    • Korean Journal of Environmental Biology
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    • v.26 no.2
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    • pp.94-101
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    • 2008
  • The aim of this study was to assess the responses of mixed function oxygenase (MFO) and antioxidative systems of feral Javelin goby, Acanthogobius hasta, caught in two sites of different pollution level in Shihwa lake, which has been a highly polluted lake by organic pollutants from nearby industrial complexes and sites. Enzymes analyzed in phase I of MFO system are cytochrome P450 (CYP), NADPH-cytochrome P450 reductase (P450R), NADH-cytochrome b5 reductase (b5R), and ethoxyresorufin deethylase (EROD). Phase II enzyme of glutathione S-transferase (GST) in MFO system was also investigated. Moreover, oxidative-enzyme system including catalase (CAT), glutathione reductase (GR) and total-glutathione peroxidase (GPX) activities and glutathione concentration in both of oxidized (GSSG) and reduced form (GSH) were determined. P450R, b5R, and GST activities of fish are relatively high in the polluted area, whereas hepatic EROD activity levels of fish in polluted area were lower than those of unpolluted area. CYP concentrations are not different between areas. These results indicated that feral Acanthogobius hasta were adaptive to highly polluted environment and exposed to oxidative stress in Shihwa lake.

ANTAGONISTIC EFFECTS OF INTERFERONS (INFs) AND SODIUM ORTHOVANADATE ON RESPONSES PRODUCED BY TCDD IN SEVERAL CULTURE SYSTEMS

  • Kim, Hwan-Mook
    • Toxicological Research
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    • v.7 no.2
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    • pp.239-255
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    • 1991
  • Several types of IFNs were tested for their ability to suppress TCDD-inducible P-450 dependent mixed function oxidase (MFO) system in mouse primary hepatocytes. Mouse IFN-gamma (IFN-G) markedly suppressed EROD activity when added at the same time as TCDD (10 nM). The antagonism of EROD activity by IFN-G exhibited both a dose-(10-100 U/ml) and time-depedence. In contrast, mouse IFN-A/B was only moderately suppressive and only at high concentrations (500 U/ml). Rat IFN-G was even more selective than mouse, wherase human IFN-G had no activity.

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Effects of Catechin on Mixed Function Oxidase System and Oxidative Damage in Rat Liver Exposed to Microwave (전자파 조사 흰쥐 간조직의 Mixed Function Oxidase System과 산화적 손상에 미치는 Catechin의 영향)

  • 김미지;이준하;이순재
    • Journal of Nutrition and Health
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    • v.34 no.3
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    • pp.299-305
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    • 2001
  • The purpose of this study was to investigate the effects of catechin on the changes of microsomal mixed function oxidase(MFO) system and oxidative damage in rat liver exposed to microwave. Sprague-Dawley male rats weighing 200$\pm$10g body weight were randomly assigned to one normal and microwave exposed groups: microwave exposed groups were divided three groups: catechin free diet(MW) group, 0.25% catechin(MW+0.25C) group and 0.5% catechin(MW+0.5C) group to the levels of dietary catechin supplementation. The rats were irradiated with microwave at frequency 2.45GHz for 15 min and then the changes pattern of mixed function oxidase system and oxidative damage were investigated for 16 days. The activity of XOD in MW group was increased from 4 day to 8 days after irradiation, compared to normal group and decreased to the level of normal group 16 days. But catechin supplementation group were maintained to the normal level. The contents of cytochrome P(sub)450 and NADPH cytochrome P(sub)450 reductase activities in liver of MW group was increased from 4 day to 8 day after irradiation, compared to normal group and decreased to the level of normal group at 16 day. But catechin supplementation group were recovered to the normal level. The contents of superoxide radical in liver of MW group was increased 1.28, 1.25, 1.17 fold of normal group at 4,6 and 8 days days after irradiation. respectively, but catechin supplementation group were maintained the normal level. The contents of lipifuscin in liver have a same tendency in superoxide radical contents. These result suggested that the supplementation of catechin have control the mixed function oxidase system and oxidative damage and that may help to recover tissues from microwave damage. (Korean J Nutrition 34(3) : 299~305, 2001)

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Microsomal Mixed Function Oxidase and Lipid Peroxidation in Liver and Lung of Sterptozotocin-Induced Diabetic Rats (Streptozotocin 유발 당뇨쥐의 간장 및 폐조직에서의 Microsomal Mixed Function Oxidase System과 과산화지질 생성)

  • 이순재;김관유
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.25 no.1
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    • pp.21-26
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    • 1996
  • 본 연구는 streptozotocin 유발 당뇨쥐에서의 MFO계활성 변화 및 이에 지질과산화를 관찰하고자 체중이 140kg 내외의 Sprague-Dawley 종 흰쥐 숫컷을 대조군과 당뇨 유발 시험군으로 나누어 4주간 사육하였다. 당뇨군은 STZ로 당뇨를 유발시켰으며 당뇨 유발 6일후 쥐를 희생기켜 간조직 및 폐조직 microsome 중의 cytochrome $P_{450}$ 및 cytochrome $b_[5}$ 함량과 NADPH-cytochrome $P_{450}$ reductase 활성도를 측정하고 아울러 microsome내의 지질과산화물을 측정하여 다음과 같은 결과를 얻었다. 실험군간에 식이 섭취량은 차이가 없었으나, 체중 증가량과 식이 효율은 당뇨군이 STZ군에 비해 현저하게 감소하였다. 간장 및 폐조직의 무게는 대조군과 당뇨군간에 유의적인 차이는 없었다. 간조직 및 GP조직 중의 cytochrome $P_{450}$ 함량은 대조군에 비해 당뇨군이 150%, 175%씩 증가하였다. 간조직 및 폐조직 중의 cytochrome $b_{5}$은 대조군에 비해 당뇨군이 53%,116%씩 각각 증가하였다. 간조직에서의 NADPH-cytochrome $P_{450}$ reductase 활성은 당뇨군이 대조군에 비해 46% 증가하였으며, 폐조직에서는 75%증가하였다. 지질과산화물가는 당뇨군이 대조군에 비해 간족에서는 약 95% 높았으며 폐조직에서는 73%높았다. 이상의 결과에서 STZ 유발 당뇨쥐에서는 MFO system의 활성도가 대조군에 비해 현저하게 증가되고 지질과산화반응이 같으 srudgid이 촉진되었으며 폐조직에서도 간조직에서와 비슷한 경향이었다. 이러한 것은 당뇨군에서는 MFO system의 활성증가로 free radical 생성이 증가되고 그 결과 지질과산화가 촉진되었다고 볼 수 있다.

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Potentiation of Carbon Tetrachloride Hepatotoxicity induced by Repeated Physical Exercise in adult Female rats (백서의 반복적인 육체운동에 의한 사염화탄소 간독성의 증폭효과)

  • Kim, Su-Nyeon;Kim, Young-Chul
    • Toxicological Research
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    • v.8 no.2
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    • pp.265-272
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    • 1992
  • Effects of repeated physical exercise on the carbon tetrachloride ($CCl_4$) hepatotoxicity were examined in adult female rats. Rats were introduced into a cylindrical rotating cage and forced to exercise for 1 hr each day, 6days/week, for 5 consecutive weeks at a speed starting from 10m/min, increased by 1m/min per day until the speed reached 27m/min. Significantly less body weight gain was observed in the exercise group suggesting that physical fitness had been induced in these animals. Eighteen hours following termination of the last exercise bout rats were treated with $CCl_4$(2 mmol/kg.ip). The $CCl_4$-induced heptotoxicity was significantly potentiated in the repeated exercise group compared to the resting sedentary animals as determined by changes in serum sorbitol dehydrogenase (SDH), glutamic oxaloacetic transaminase(GOT), glutamic pyruvic transaminase (GPT), and glucose-6-phosphatase(G-6-Pase) activities when measured 24hrs following the $CCl_4$ treatment. Hepatic drug metabolizing activity was determined in order to elucidate the underlying mechanism of potentiating action of the $CCl_4$ hepatotoxicity induced by repeated physical exercise. Repeated exercise increased the hepatic microsomal cytochrome P-450 contents and aminopyrine N-demethylase activity. The results suggest that the potentiation of $CCl_4$ hepatotoxicity by repeated exercise is associated with induction of the mixed function oxidase (MFO) enzyme system mediating the metabolism of $CCl_4$ to its active metabolite(s).

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신물질의 간독성 평가방법 개발 및 기작에 관한 연구

  • 차영남
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.97-97
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    • 1993
  • 본 연구과제에서는 적출판류간실험법 (isolated perfused liver technique)을 약물의 간독성 유발 및 보간작용에 관한 실험법으로 개발하고자 butylated hydroxyanisole (BHA) 을 이용하여 보간실험을 하였다. BHA를 식이투여한 흰쥐로부터 적출한 간에 간독성 모델물질로 2,6-dichlorophenolindophenol (DCPIP) 을 관류시켜 관류액내의 DCPIP의 유리형, 환원형, glucuronide, sulfate 포합체의 대사체를 측정하여 DCPIP 외 대사양상을 관찰하였으며, 동시에 간세포 손상으로 관류액내로 유출된 lactate dehydrogenase (LDH)의 활성도를 측정하여 DCPIP예 의할 간세포독성 유발정도를 간접적으로 측정하여 대조군과 비교하였다. 그리고 BHA에 의한 보간작용이 약물대사효소의 변와에 기인한 것인가를 관찰하기 위하여 모델약물로 7-ethoxycoumarin (EC) 이나 EC의 phase I 대사산물인 7-hydroxycoumarin (HC) 을 관류시켜 관류액내의 HC의 유리체, glucuronide 포합체, sulfate 포합체로의 대사량을 측정하여 약물대사시 약물의 활성화에 관계하는 phase I mixed function oxidase (MFO) 효소와 약물의 해독화에 관계하는 phase II 포합효소 (UDP-glucuronyltranesferase(UDPGT)와 sulfotransferase (ST))의 활성도 변화를 측정하여 대조군과 비교하였다. 간독성 모델물질인 DCPIP를 적출한 흰쥐의 간에 관규시켰을때 BHA 전처리군이 LDH가 유출되기 시작하는 시간이 대조군에 비하여 유의적으로 늦었으며, LCH가 유출량도 유의적으로 감소되어 DCPIP에 의한 간독성 유발능력이 BHA에 의하여 감소됨을 관찰하였다. 아울러 DCPIP의 대사체중 환원체와 glucuronide 포합체의 생성량이 증가되어 BHA에 의하여 quinone reductase와 UDPGT 활성도가 증가되었음을 알 수 있었다. 그리고 BHA 전처리에 의하여 MFO효소계와 ST의 활성도에는 변화가 없었으나 UDOGT 의 활성도는 약 2.2배 증가되었다. 이상의 결과로 BHA에 의한 보간작용은 간독성 물질을 활성화시키는 phase I MFO 효소의 활성도에는 변화없이 해독작용에 관여하는 phase II효소들의 활성도 증가에 기인된 것을 알 수 있었다. 그리고 이러한 결과는 적출한 관류간실험법은 여러 약물의 보간효과를 관찰하는 실험법으로 적합할 것으로 사료되었다.

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Maximum Power Point Tracking of Photovoltaic using Improved Particle Swarm Optimization Algorithm (개선된 입자 무리 최적화 알고리즘 이용한 태양광 패널의 최대 전력점 추적)

  • Kim, Jae-Jung;Kim, Chang-Bok
    • Journal of Advanced Navigation Technology
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    • v.24 no.4
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    • pp.291-298
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    • 2020
  • This study proposed a model that can track MPP faster than the existing MPPT algorithm using the particle swarm optimization algorithm (PSO). The proposed model highly sets the acceleration constants of gbest and pbest in the PSO algorithm to quickly track the MPP point and eliminates the power instability problem. In addition, this algorithm was re-executed by detecting the change in power of the solar panel according to the rapid change in solar radiation. As a result of the experiment, MPP time was 0.03 seconds and power was 131.65 for 691.5 W/m2, and MPP was tracked at higher power and speed than the existing P&O and INC algorithms. The proposed model can be applied when a change in the amount of power is detected by partial shading in a Photovoltaic power plant with Photovoltaic connected in parallel. In order to improve the MPPT algorithm, this study needs a comparative study on optimization algorithms such as moth flame optimization (MFO) and whale optimization algorithm (WOA).

Meta-heuristic optimization algorithms for prediction of fly-rock in the blasting operation of open-pit mines

  • Mahmoodzadeh, Arsalan;Nejati, Hamid Reza;Mohammadi, Mokhtar;Ibrahim, Hawkar Hashim;Rashidi, Shima;Mohammed, Adil Hussein
    • Geomechanics and Engineering
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    • v.30 no.6
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    • pp.489-502
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    • 2022
  • In this study, a Gaussian process regression (GPR) model as well as six GPR-based metaheuristic optimization models, including GPR-PSO, GPR-GWO, GPR-MVO, GPR-MFO, GPR-SCA, and GPR-SSO, were developed to predict fly-rock distance in the blasting operation of open pit mines. These models included GPR-SCA, GPR-SSO, GPR-MVO, and GPR. In the models that were obtained from the Soungun copper mine in Iran, a total of 300 datasets were used. These datasets included six input parameters and one output parameter (fly-rock). In order to conduct the assessment of the prediction outcomes, many statistical evaluation indices were used. In the end, it was determined that the performance prediction of the ML models to predict the fly-rock from high to low is GPR-PSO, GPR-GWO, GPR-MVO, GPR-MFO, GPR-SCA, GPR-SSO, and GPR with ranking scores of 66, 60, 54, 46, 43, 38, and 30 (for 5-fold method), respectively. These scores correspond in conclusion, the GPR-PSO model generated the most accurate findings, hence it was suggested that this model be used to forecast the fly-rock. In addition, the mutual information test, also known as MIT, was used in order to investigate the influence that each input parameter had on the fly-rock. In the end, it was determined that the stemming (T) parameter was the most effective of all the parameters on the fly-rock.

Development of Anticancer Prodrugs and Tumor Specific Adjuvant Prodrugs for Chemotherapy

  • Moon, Ki-Young
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2000.04a
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    • pp.8-9
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    • 2000
  • Despite the advances made in the past few decades in cancer chemotherapy, many conventional anticancer drugs display relatively poor selectivity for cancer cells. The nonselectivity of anticancer drugs and the development of anticancer drug resistance have been recognized as serious limitations in their clinical usefulness. Therefore, a major challenge in cancer chemotherapy is the development of new anticancer agents with improved selectivity for tumor cells as well as the prevention of the host cell resistance, both of which result in the improvement of therapeutic effect against cancer cells. Cyclophosphamide (CP), a widely used anticancer agent, is a prodrug that is activated by hepatic microsomal mixed-function oxidase (MFO) catalyzed C$_4$- hydroxylation. The resulting 4-hydroxycyclophosphamide (4-OH-CP) is converted to the ring-opened tautomer to aldophosphamide (Aldo) which subsequently undergoes a base- catalyzed ${\beta}$-elimination to generate cytotoxic phosphoramide mustard (PDA) and acrolein. The cytotoxic activity of CP is attributed to the aziridinium ion species derived from PDA that cross-links interstrand DNA.

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Toxic action of benfuracarb via oxidative bioactivation process by cytochrome $P_{450}$ (Procarbamate계 살충제 benfuracarb의 산화적 활성화 과정을 통한 독성발현)

  • Yu, Yong-Man;Kim, Eun-H.;Kim, Song-Mum;Hur, Jang-Hyun
    • The Korean Journal of Pesticide Science
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    • v.7 no.1
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    • pp.45-50
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    • 2003
  • This study was conducted to understand the role of oxidative enzyme cytochrome $P_{450}$ in the bioactivation of benfuracarb and to know metabolites of benfuracarb by cytochrome $P_{450}$. The bimolecular imhibition rate constant $(k_i)$ of benfuracarb on acetylcholinesterase (AChE) was as low as $1.1{\times}10^3\;M^{-1}\;min^{-1}$, suggesting that benfuracarb should be activated for its toxic action. The potency of benfuracarb on AChE in the oxidase system (cytochrome $P_{450}$ + NADPH) in vitro was 10-fold higher than that of control (cytochrome $P_{450}$). Such a similar result was also found in the oxidase + PBO system. In vivo the $I_{50}$ of benfuracarb was 22.7mg $kg^{-1}$, but pie-treatment of piperonyl butoxide (PBO) reduced the $I_{50}$ by >100mg $kg^{-1}$. This result suggests that cytochrome $P_{450}$ was involved in the activation of benfuracarb. Using microsomal oxidase system, metabolites of benfuracarb were elucidated. Fifty-eight percent of benfuracarb was converted to carbofuran, a major toxic metabolite, in the oxidase system, while only less than two percent of benfuracarb was converted to carbofuran in the oxidase + PBO system. These results also suggest that cytochrome $P_{450}$ was involved in the activation of benfuracarb. Overall results indicate that cytochrome $P_{450}$ could be involved in the bioactivation of benfuracarb to carbofuran.