• Title/Summary/Keyword: NADH cytochrome b5 reductase

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Modulation of Cytochrome P-450 Induction by Long-Term Supplementation with Korean Red Ginseng to Rats (홍삼의 장기 투여가 흰쥐 간 대사효소 유도에 미치는 영향)

  • Lim, Heung-Bin
    • Korean Journal of Medicinal Crop Science
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    • v.15 no.6
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    • pp.437-443
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    • 2007
  • This study was carried out to investigate the effect of dietary supplementation with red ginseng water-extracts on the induction of microsomal cytochrome P-450 in rats. Phenobarbital (PB) and 3-methylcholanthrene (3-MC), P-450 inducers, were administered to 3- or 12-month old rats received red ginseng extracts (25 mg/kg) from 6 weeks to 12 months for 3 days. PB and 3-MC increased levels of P-450, P-450 reductase, ethoxycoumarin O-deethylase, benzphetamine N-demethylase and glutathione-S-transferase in the liver of rats. However, chronic administration of red ginseng significantly reduced these increase of enzyme levels induced by P-450 inducers. Chronic administration of red ginseng did not affect the induction of cytochrome $b_5$ and NADH cytochrome $b_5$ reductase by P-450 inducers. It is suggested that the induction of cytochrome P-450 system in the liver in relation to xenobiotics toxicity can be modulated by long-term supplementation with Korean red ginseng to rats.

Gender Differences in Activity and Induction of Hepatic Microsomal Cytochrome P-450 by 1-Bromopropane in Sprague-Dawley Rats

  • Kim, Ki-Woong;Kim, Hyeon-Yong;Park, Sang-Shin;Jeong, Hyo-Seok;Park, Sang-Hoi;Lee, Jun-Yeon;Jeong, Jae-Hwang;Moon, Young-Hahn
    • BMB Reports
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    • v.32 no.3
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    • pp.232-238
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    • 1999
  • Sex differences in the induction of microsomal cytochrome P-450 (CYP) and the activities of several related enzymes of Sprague-Dawley rats treated with 1-bromopropane (1-BrP) were investigated. Male and female rats were exposed to 50, 300, and 1800 ppm of 1-BrP per kg body weight (6 h a day,S days a week, 8 weeks) by inhalation. The mean body weight of 1-BrP treated groups increased according to the day elapsed, but four and five weeks respectively after the start of the exposure, the mean body weight of male and female rats had significantly reduced in the group treated with 1800 ppm 1-BrP compared with the control group (p<0.01). While the relative weights of liver increased in both sexes, statistical significance in both sexes was found only in the group receiving 1800 ppm/kg of 1-BrP (p<0.01). The total contents of CYP, $b_5$, NADPH-P-450 reductase, NADH $b_5$ reductase, ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-dealkylase (PROD), and p-nitrophenol hydroxylase (pNPH) activities were examined for the possible effects of 1-BrP. No significant changes in the CYP and $b_5$ contents, NADPH-P-450 reuctase, NADH $b_5$ reductase, ethoxyresorufin-O-deethylase (EROD), and pentoxyresorufin- O-dealkylase (PROD) were observed between the control and treated groups. The activity of pNPH increased steadily with the increase in the concentration of 1-BrP in both sexes, but was significantly increased only in the 1800 ppm-treated group of male rats (p<0.05). When Western blottings were carried out with three monoclonal antibodies (MAb 1-7-1, MAb 2-66-3, and MAb 1-98-1) which were specific against CYP1A1/2, CYP2B1/2, and CYP2E1, respectively, a strong signal corresponding to CYP2E1 was observed in microsomes obtained from rats treated with 1-BrP. Glutathione S-transferase (GST) activity and the content of lipid peroxide significantly increased in the treated groups compared with the control group (p<0.05). These results suggest that 1-BrP can primarily induce CYP2E1 as the major form and that GST phase II enzymes play important roles in 1-BrP metabolism, showing sex-dependence in the metabolic mechanism of 1-BrP in the rat liver.

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The Effect of Korean Red Ginseng Water-extract on Aging-related Changes in the Xenobiotic Metabolizing Enzyme System in the Liver of Rats (홍삼의 물추출물이 노화에 따른 흰쥐 간의 이물질대사 효소계에 미치는 영향)

  • Lee, Dong-Wook;Lim, Heung-Bin
    • Korean Journal of Medicinal Crop Science
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    • v.14 no.6
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    • pp.329-335
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    • 2006
  • The present study was designed to investigate aging-related effects on the activities of xenobiotic metabolizing enzymes of rat liver by dietary supplementation of Korean red ginseng water-extract. Rat did not show any discernible signs of the rejection symptoms, and blood GOT and GPT levels were not influenced by ginseng water extracts, Cytochrome 450 levels and NADPH cytochrome P45O reductase, p-450 dependent ethoxycoumarin O-deethylase, and benzphetamine N-demethylase activities were decreased with aging, however, these phase I system enzymes activities in the ginseng group of24 months were well maintained compared with normal group. But, Levels of cytochrome bs and NADH-cytochrome b$_5$ reductase activities were also decreased with aging and were not found a clear difference between two groups. Glutathione-s-transferase activity, phase II enzyme system, in liver cytosols was also decreased in old ages, but the degree of decrease was higher in normal group than in giuseng supplemented group. These results indicate that long-term supplementation of red ginseng water extracts from weaning to 24 months do not show any side effects to rats, and retard age-related deteriorations of xenobiotic metabolizing enzymes activities in old ages.

Induction of Hepatic Microsomal Cytochrome P450 by N,N-dimethylformamide in Sprague-Dawley Rats (흰쥐에서 N,N-dimethylformamide에 의한 간장의 Microsomal Cytochrome P450의 유도)

  • Koh, Sang-Baek;Cha, Bong-Suk;Kang, Seung-Kyu;Joung, Hyo-Seok;Kim, Ki-Woong
    • Journal of Preventive Medicine and Public Health
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    • v.32 no.1
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    • pp.88-94
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    • 1999
  • Objectives. In order to gain a better understanding of the mechanism of DMF toxicity, recent studies have focused on hepatic drug metabolizing enzymes. In this study, we investigated the effects of DMF on the induction of P450 and the activities of other related enzymes in rat liver microsomes. Methods. DMF was administered to male Sprague Daweley rats by intraperitoneal injection at 0(control), 450(D1), 900(D2), 1,800(D3) mg DMF/kg body weight in olive oil once a day for three days. Hepatic P450 was measured by method of Omura and Sato. We evaluated selective assays for the three drug metabolizing cytochrome P450 isoenzymes 1A1, 2B1 and 2E1. Results. The content of microsomal protein, P450 and b5 were tended to be decreased in DMF treated group, but they were not statistically significant. The activity of NADPH-cytochrome P450 reductase was significantly increased dose dependently(p<0.01), but the activity of NADH-b5 reductase was decreased in the treated group(p<0.01). The activities of PROD and EROD were not significant between control and treated group. The activities of pNPH in the DMF treated groups were higher than that of the control group(p<0.01). When Western immunoblottings were carried out utilizing three monoclonal antibodies which were specific against P4501A1/1, P4502B1/2 and P4502E1, the strong density band corresponding to P4502E1 was observed with the microsomes obtained from the rats treated with DMF. But there were no significant increased in the P4501A1/2 and P4502B1/2 band densities in immunoblotting. Conclusions. These result suggested that P4502E1 was inducible by DMF and P4502E1 isozyme might be responsible for the hydroxylation of DMF to HMMF.

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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.

Effects of Ethanol on the Activities and Inducibility of Trichloroethylene Metabolic Enzyme System in Rat Liver (Ethanol이 Trichloroethylene 대사효소의 활성도와 유도성에 미치는 영향)

  • Kim, Ki-Woong;Kang, Seung-Kyu;Cho, Young-Sook;Lee, Sei-Hui;Moon, Young-Hahn;Choi, Byung-Soon;Park, Sang-Shin
    • Journal of Preventive Medicine and Public Health
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    • v.28 no.1 s.49
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    • pp.141-152
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    • 1995
  • This study was performed to find out the influences of ethanol on the metabolism of trichloroethylene(TRI) in rats. TRI in corn oil at the dosage of 150, 300, 600 mg/kg was injected peritoneally once a day for two days to two groups. In one group ethanol(4 g/kg) was taken orally 30 minutes before TRI injection, and the other group ethanol was not. The results of experiments are as follows: 1. The contents of cytochrome P-450 and $b_5$ had inverse relationship with in-jected TRI amounts in both groups. 2. The activity of NADPH P-450 reductase was decreased slowly in TRI injected group related with TRI amount, but decreased drastically in the group pretreated with ethanol. 3. The activity of NADH $b_5$ reductase had relationship with injected nt amount , but the statistical significance was found only in the groups of 300 and 600 mg/kg of TRI injected without relevance to ethanol when compared with the group that was not injected. 4. The activity of ADH was more decreased and ALDH activity was more increased in groups that TRI injected and ethanol was pretreated with ethanol groups than in group without any treatment. These results suggest that ethanol may inhibit epoxide formulation, the first step of TRI metabolism, and change from TCE-OH to TCA also.

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