• Title/Summary/Keyword: Cytochrome P450 isozyme

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The Effects of Palmulgunja-tang(八物君子湯)Enzyme Activity on Cytochrome P450 Isozyme (팔물군자탕(八物君子湯) Cytochrome P450 효소(酵素) 활성에 미치는 영향)

  • Ryu, Jung-Man;Park, Seong-Sik
    • Journal of Sasang Constitutional Medicine
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    • v.17 no.2
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    • pp.64-73
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    • 2005
  • 1. Objectives The purpose of this study was to investigate the effects of the enzyme activity of Palmulgunja-tang with administered orally solution on cytochrome P450 isozyme 2. Methods This study was carried on through following methods. We treated the rat with the {3-naphthoflavone (${\beta}NF$) of 80mg/kg for 3 days i.p injection. Firstable, microsomal protein was separated and total intracellular protein test was done. Then GOT and GPT were measured and assay of cytochrome P450 IAI/2 enzyme activity was performed according to the method of EROD and MROD. (Ethoxyresorufin-O-deethylase(EROD) activity was used to measure cytochrome P450 lAI activity and methoxyresorufin O-demethylase(MROD) activity was used to measure cytochrome P450 lA2 activity. ) 3. Results and Conclusions 1) PGT recovered the liver damage on ${\beta}NF$ inducible CYP IAI/2 by pre-post and high-low condition. 2) At concentration of post-treated 50mg!kg of PGT, the inhibiting of $\betaNF$ metabolites to liver of rat cytochrome P450 lAl was inhibited by 53.0% respectively. 3) PGT showed 36.0% inhibition of ${\beta}NF$-induced lA2 activity at the concentration post-treated 50mg/kg.

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Role of Cytochrome P-450 in the Bioactivation of Nicotine

  • Kim, Bong-Hee;Anthony Travor
    • Archives of Pharmacal Research
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    • v.14 no.2
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    • pp.130-136
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    • 1991
  • Nicotine (100 .mu. M) was incubated with microsomes (1 mg/ml) prepared from New Zealand White rabbits. On the basis of microsomal weight, the rate of nicotine oxidation were calculated on the basis of cytochrome P-450 concentration, the specific activity of the metabolic oxidation catalyzed by lung was approximately 4 times greater than liver (6.4 vs 1, 65 nmoles nicotine oxidized. nmole cytochrome $P-450^{-1}\;min{-1})$. These studies employed several methods of altering activities of specific isozymes present in pulmonary microsomes, including the use of the isozyme2 and 6 specific inhibitor $\alpha$-methylbenzyl ABT, metabolite inhibitors, norbenzphetamine and N-hydroxyamphetamine. TCDD induction and Arochlor 1260 pretreatment. These results support the conclusion that nicotine metabolism by rabbit lung microsomes is mediated primarily by cytochrome P-450 isozyme 2.

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Rabbit Liver and Lung Microsomal Metabolism of $\beta$-Nicotyrine:Isozyme Specificities toward the Oxidation of $\beta$-Nicotyrine

  • ;Mark K. Shigenaga
    • Environmental Mutagens and Carcinogens
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    • v.9 no.2
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    • pp.87-96
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    • 1989
  • Studies on the biodisposition of beta-nicotyrine by lung and liver microsomes was examined in order to provide a better understanding of its fate in this tissue. beta-nicotyrine (100$\mu$M) was incubated with microsomes (1 mg/ml) prepared from New Zealand White rabbits. The rate of oxidation observed in lung microsomal incubations was 1.7 nmoles $\beta$-nicotyrine oxidized mg$^{-1}$ min$^{-1}$ compared with 2.7 nmoles $\beta$-nicotyrine oxidized mg$^{-1}$ min$^{-1}$ by the liver microsomal preparation. However, when these rates were expressed as a function of cytochrome P-450 content, the specific activity of the metabolic oxidation catalyzed by lung (8.3 nmoles $\beta$-nicotyrine oxidized nmole cytochrome P-450$^{-1}$ min$^{-1}$) was approxiamtely 4 times greater than liver microsomes (2.3 nmoles $\beta$-nicotyrine oxidized nmole cytochrome P-450$^{-1}$ min$^{-1}$). Isozyme studies on the oxidation of $\beta$-nicotyrine employed several methods of altering activities of specific isozymes present in pulmonary microsomes, including the use of the isozyme 2 and 6 specific inhibitor $\alpa$-methyl ABT, metabolic inhibitor(MI) complex formation. The results of this inhibition study would appear to indicate the $\beta$-nicotyrine is metabolized predominantly by pulmonary isozyme 5.

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Effect of Ramaria botrytis Methanol Extract on Hepatotoxicity in Benzo(α) Pyrene-treated Mice and Expression of Cytochrome P-450 1A1 Isozyme (벤조피렌 유발 마우스에서 싸리버섯 메탄올 추출물의 간 독성 억제효과 및 사이토크롬 P-450 1A1 Isozyme의 발현에 미치는 영향)

  • Kim, Hyun-Jeong;Lee, In-Seon;Bae, Jun-Tae;Kim, Ok-Mi;Park, Sun-Hee;Chang, Jong-Sun;Park, Jun-Hong;Lee, Kap-Rang
    • The Korean Journal of Mycology
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    • v.31 no.1
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    • pp.34-39
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    • 2003
  • This study was conducted to investigate effects of Ramaria botrytis methanol extract on liver damage in benzo$({\alpha})$pyrene(B$({\alpha})$P)-treated mice. The activities of serum amminotransferase, cytochrome P-450, aminopyrine N-demethylase, aniline hydroxylase and hepatic content of lipid peroxide after B$({\alpha})$P-treatment were increased than control, but those levels were significantly decreased by the treatment of Ramaria botrytis methanol extract. Whereas, the hepatic glutathione content and activities of glutathionie S-transferase and r-glutamylcysteine syntherase were increased by the treatment of Ramaria botrytis methanol extract. In addition, cytochrome P-450 1A1 izozyme protein level, remarkably increased by B$({\alpha})$P-treatment was decreased by the treatment with methanol extract of Ramaria botrytis. These results suggest that the protective effect of methanol extract of Ramaria botrytis on liver injury in B$({\alpha})$P-treated mice may be due to reduction of oxygen free radical.

Alterations in Dichloromethane-Induced Carboxyhemoglobin Elevation by Several Metabolic Modulators (이염화메탄에 의한 Carboxyhemogolbin 생성에 몇몇 대사활성조절제들이 미치는 영향)

  • 강경애;김영철
    • Toxicological Research
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    • v.11 no.2
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    • pp.273-277
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    • 1995
  • Several metabolic modulators on the generation of carbon monoxide (CO)from dichloromethane (DCM) was examined in adult female rats. It has been known that DCM is converted to CO by cytochrome P-450 or to carbon dioxide $(CO_2)$ by glutathione-dependent metabolic reaction. In rats treated with DCM (3 mmol/kg, ip) only, the carboxyhemoglobin (COHb) level reached a peak of approximately 10% 2 or 3 hr following the treatment. Disulfiram (300 mg/kg, ip) or allylsulfide (200 mg/kg, po), both known as a selective inhibitior for cytochrome P-450 2E1, blocked the increase in COHb concentratlons almost completely suggesting that the metabolic conversion of DCM to CO is mediated by the activity of this specific type of isozyme. YH439 (125 or 250 mg/kg, po), a potential hepatoprotective agent, decreased the COHb elevation as well indicating that this chemical is a potent inhibitor for 2E1. In rats treated with pyrazine (200 mg/kg, ip) 18 hr prior to DCM the peak COHb concentration was decreased by approximately 3 or 4%. However, pretreatment of rats with pyrazine either 24 or 48 hr before DCM increased the peak COHb concentration significantly compared to the rats treated with DCM only. The results in the present study strongly suggest that the generation of CO from DCM depends on the 2E1 activity and that the pharmacological and/or toxicological action of YH439 or pyrazine in animals or human is associated with its effect on this isozyme.

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Differential Regulation of Cytochrome P450 Isozyme mRNAs and Proteins by Femur Fracture Trauma

  • Lee, Woo-Young;Lee, Sun-Mee
    • Archives of Pharmacal Research
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    • v.26 no.12
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    • pp.1079-1086
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    • 2003
  • The aim of this study was to investigate the effect of trauma on cytochrome P450 (CYP) gene expression and to determine the role of Kupffer cells in trauma-induced alteration of CYP isozymes. Rats underwent closed femur fracture (FFx) with associated soft-tissue injury under anesthesia. To deplete Kupffer cells in vivo, gadolinium chloride ($GdCl_3$) was intravenously injected at 7.5 mg/kg body wt., 1 and 2 days prior to FFx surgery. At 72 h of FFx, liver tissues were isolated to determine the mRNA and protein expression of CYP isozymes and NADPH-P450 reductase by reverse transcription-polymerase chain reaction and Western immunoblotting, respectively. In addition, the mRNA levels of tumor necrosis factor alpha (TNF-$\alpha$), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) were evaluated. FFx increased the mRNA level of CYP1A1; an increase that was not prevented by $GdCl_3$. There were no significant differences in the mRNA expression of CYP1A2, 2B1 and 2E1 among any of the experimental groups. The protein levels of CYP2B1 and 2E1 were significantly decreased by FFx; a decrease that was not prevented by $GdCl_3$ treatment. The gene expression of NADPH-P450 reductase was unchanged by FFx. FFx significantly increased the expression of TNF-$\alpha$ mRNA; an increase that was attenuated by $GdCl_3$. The mRNA expression of HO-1 was increased by FFx, but not by $GdCl_3$ . Our findings suggest that FFx differentially regulates the expression of CYP isozyme through Kupffer cell-independent mechanisms.

In Vitro Enhancement of Microsomal Cytochrome P450-Dependent Monooxygenases by Organic Solvents in Rat Liver

  • Lee, Dong-Wook;Lim, Heung-Bin;Moon, Ja-Young;Park, Ki-Hyun
    • BMB Reports
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    • v.31 no.4
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    • pp.391-398
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    • 1998
  • In vitro effects of acetone, methanol, and dimethylsulfoxide (DMSO) on liver microsomal cytochrome P450 (P450) content, and P450-dependent arylhydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (ECOD) activities were studied in rats. Acetone at 1% (v/v) enhanced the content ofP450, assayed spectrally in 3-methylcholanethrene (MC)- and ${\beta}-naphthoflavone$ (BNF)-inducible microsomes by 18 and 7%, respectively. Methanol, up to 5% (v/v) applied, also showed enhancement effects on P450 content in liver microsomes from rats treated with phenobarbital (PB), MC, and BNF, as well as uninduced microsomes with similar but low strength. DMSO, however, did not show such enhancing effects at the ranges of the concentrations applied. AHH and ECOD activities in MC-inducible microsomes were also enhanced by acetone at 1%, which was in proportion to the increase in P450 content by the same concentration. However, the P450 content, and AHH and ECOD activities, were decreased by increasing the concentration of acetone. Methanol at the same concentration with acetone also enhanced ECOD activity but not AHH activity in MCinducible microsomes. The enhancing effect of acetone on the enzymes was negligible when the microsomes were pretreated with a specific monoclonal antibody of MC-inducible isozyme. The difference in the effects of these solvents on P450 system might be due to their different properties that cause the P450 active site to be exposed in milieu.

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Preventive Effect of Sarcodon aspratus Extract on the Liver Damage in B(a)P-Treated Mice (벤조피렌을 투여한 마우스에서 향버섯 추출물의 간 손상 예방 효과)

  • 이갑랑;배준태;장종선;박준홍;박선희;김지영;오은정;김현정;김옥미
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.30 no.2
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    • pp.320-324
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    • 2001
  • To investigate the effect of Sarcodon aspratus methanol extract on liver damage in benzo(a)pyrene (B(a)P)-treated mice, mice were divided into 4 groups of control, B(a)P, Sarcodon aspratus methanol extract and Sarcodon aspratus methanol extract-B(a)P. The activities of serum aminotransferase, cytochrome P-450 and hepatic content of lipid peroxide after B(a)P-treatment were increased than control, but those levels were significantly decreased by the treatment of Sarcodon aspratus methanol extract. On the other hand, the hepatic glutathione content and glutathione S-transferase activity were increased by the treatment of Sarcodon aspratus methanol extract. Also the activities of superoxide dismutase, catalase and glutathione peroxidase were decreased by the treatment of Sarcodon aspratus methanol extract. In addition cytochrome P-450 1A1 isozyme protein level, which was remarkably increased by B(a)P treatment from results of immuno blotting, was decreased by the treatment with methanol extract of Sarcodon aspratus. These results suggest that Sarcodon aspratus methanol extract have protective effect on liver damage by decreasing lipid peroxide and activities of free radical generating enzymes.

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Trolox C Ameliorates Hepatic Drug Metabolizing Dysfunction After Ischemia/Reperfusion

  • Eum, Hyun-Ae;Lee, Sang-Ho;Lee, Sun-Mee
    • Archives of Pharmacal Research
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    • v.25 no.6
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    • pp.940-945
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    • 2002
  • The present study was done to determine the effect of trolox C, a hydrophilic analogue of vitamin E, on hepatic injury, especially the alteration in cytochrome P-450 (CYP)-dependent drug metabolism during ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Rats were treated intravenously with trolox C (2.5 mg/kg) or vehicle (PBS, pH 7.4), 5 min before reperfusion. Serum alanine aminotransferase and lipid peroxidation levels were markedly increased after I/R. This increase was significantly suppressed by trolox C. Cytochrome P-450 content was decreased after I/R but was restored by trolox C. There were no significant differences in ethoxyresorufin O-dealkylase (CYP 1A1) and methoxyresorufin O-dealkylase (CYP 1A2) activities among any of the experimental groups. Pentoxyresorufin O-dealkylase (CYP 2B1) activity was decreased and aniline p-hydroxylase (CYP 2E1) activity was increased after I/R. Both these changes were prevented by trolox C. Our findings suggest that trolox C reduces hepatocellular damage as indicated by abnormalities in microsomal drug-metabolizing function during I/R, and that this protection is, in part, caused by decreased lipid peroxidation.

Effects of Polycyclic Aromatic Hydrocarbons on Liver and Lung Cytochrome P450s in Mice

  • Kim, Ji-Young;Lee, Sang-Kyu;Kim, Chun-Hwa;Jeon, Tae-Won;Moon, Chang-Kiu;Lee, Hye-Sook;Yoo, Sun-Dong;Lee, Eung-Seok;Jeong, Tae-Cheon
    • Archives of Pharmacal Research
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    • v.26 no.5
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    • pp.394-404
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    • 2003
  • Certain polycyclic aromatic hydrocarbons (PAHs) have been reported to induce cytochrome P450 (CYP) 1A1 and 1A2. In the present study, the effects of six well-known PAHs, such as benzo[a]pyrene, benz[a]anthracene, dibenz[a,h]anthracene, chrysene, benzo[k]fluorancene and benzo[b]fluorancene, on the activities of hepatic and pulmonary CYP enzymes were investigated in male ICR mice. When mice were treated intraperitoneally with 3, 10 and 30 mg/kg of individual PAHs for 3 consecutive days, the activities of ethoxyresorufin- and methoxyresorufin-Ο-dealkylases were significantly and differentially induced in both liver and lung. Moreover, other CYP isozyme-associated monooxygenase activities were also induced significantly in liver and lung with characteristic induction profiles. Our present results suggest that individual PAHs might have inductive effects on CYP isozymes, and that the characteristic inductive effects of individual PAHs on certain CYP isozymes would be developed as a marker for determining exposure to certain PAHs.