• 제목/요약/키워드: Cytochrome P-450 enzymes

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노화과정(老化過程)의 흰쥐에서 보간환(補肝丸)이 간장(肝臟)의 대사효소계(代謝酵素系)에 미치는 영향(影響) (Effects of Boganhwan Decoction on the Liver Lipid Peroxide Content and Metabolic Enzyme System)

  • 조한숙;오민석;송태원
    • 혜화의학회지
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    • 제8권1호
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    • pp.711-726
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    • 1999
  • Aging in the life form occurs due to a gradual progression of the body growth and degeneration. Morphological and functional changes in the body decreases the adaptation and prevention capacity leading into the decline of a life force. Various studies have been released to examine the anti-aging effects of herbal prescriptions. This experiment has chosen Boganhwan which is used for the deficiency of the liver function and studied the anti-aging factors by examining the biotransformation enzymes. The following results were obtained in this study: 1. Hepatic lipid peroxide activity was significantly suppressed in the experimental group treated with Boganhwan for 2 weeks at the dosage of 350mg/kg, while other dosage groups did not present much changes. 2. Insignificant changes were shown for the cytochrome P-450 level, aminopyrine demethylase, and aniline hydroxylase (AH) activities. Cytochrome P-450 do not appears to be a part of the detoxification scheme. 3. Boganhwan decoction treated group showed most significant increase of superoxide dismutase (SOD), catalase, superoxide, and glutathione activities at the concentration of 350mg/kg and 500mg/kg. 4. Glutathione S-transferase and glutathione made most significant increase at the decoction concentration of 350mg/kg and 500mg/kg compared to the control group. 5. Hepatic glutathione concentration, protein bound-SH, and nonprotein bound-SH made most significant increase at the decoction concentration of 350mg/kg and 500mg/kg compared to the control group. From the above results, Boganhwan decoction played an important role in eliminating foreign substances in the body excluding cytochrome P-450 enzyme system. Thus, Boganhwan decoction can provide substantial aid in preventing and treating senile related illnesses.

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In Vitro Inhibitory Effect of Licoricidin on Human Cytochrome P450s

  • Kim, Sunju;O, Heungchan;Kim, Jeong Ah;Lee, Seung Ho;Lee, Sangkyu
    • Mass Spectrometry Letters
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    • 제5권3호
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    • pp.84-88
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    • 2014
  • Licoricidin isolated from Glycyrrhiza uralensis is known to have anticancer, anti-nephritic, anti-Helicobacter pylori, and antibacterial effects. In this study, a cocktail probe assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the modulating effect of licoricidin on cytochrome P450 (CYP) enzymes in human liver microsomes. When licoricidin was incubated at $0-25{\mu}m$ with CYP probes for 60 min at $37^{\circ}C$, it showed potent inhibitory effects on CYP2B6-catalyzed bupropion hydroxylation and CYP2C9-catalyzed diclofenac 4'-hydroxylation with half maximal inhibitory concentration ($IC_{50}$) values of 3.4 and $4.0{\mu}m$, respectively. The inhibition mode of licoricidin was revealed as competitive, dose-dependent, and non-time-dependent, and following the pattern of Lineweaver-Burk plots. The inhibitory effect of licoricidin has been confirmed in human recombinant cDNA-expressed CYP2B6 and 2C9 with $IC_{50}$ values of 4.5 and $0.73{\mu}m$, respectively. In conclusion, this study has shown the potent inhibitory effect of licoricidin on CYP2B6 and CYP2C9 activity could be important for predicting potential herb-drug interactions with substrates that mainly undergo CYP2B- and CYP2C9-mediated metabolism.

Synthesis of 2-(Allylthio)pyrazines As a Novel Cancer Chemopreventive Agent

  • Lee, Jong-Wook;Lee, Bong-yong;Kim, Nak-Doo
    • Archives of Pharmacal Research
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    • 제24권1호
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    • pp.16-20
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    • 2001
  • 2-(Allylthio)pyrazine derivatives were designed as a novel cancer chemopreventive agent that functions through selective inhibtion of cytochrome P-450 and induction of phase 11 enzymes involved in the detoxification of carcinogens. A practical preparation method of 2-(allylthio) pyrazine derivatives was established by the reaction of 2-mercaptopyrazine and allylbromides in the presence of a catalytic antioxidant, DABCO (1,4-diazabicyclo[2,2,2] octane), in dimethyl-formamide at below $50^{\circ}C$.

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흰쥐 간에 있어 지질과산화에 미치는 식이성 비타민 E의 수준 및 카페인의 영향 (Effects of Dietary Vitamin E Level and Caffeine on Lipid Peroxidation in Rat Liver)

  • 박미리;조수열
    • 한국식품영양과학회지
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    • 제23권4호
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    • pp.561-567
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    • 1994
  • This study was designed to evaluate the effects of dietary vitamin E and caffeine on the activities of lipid peroxidation related enzymes in rat liver . Male Sprague-Dawley rats were fed on diets containing three level of vitamin E (37.5, 750 or 1,5oomg/kg diet) and with or without 0.3% caffeine. The rats were sacrificed after 5 and 10 weeks of feeding. Results obtained from this study were as follows ; The content of cytochrome P450 tended to increase as dietary vitamin E level was raised. The activity of xanthine oxidase increased in the caffeine groups, but it decreased by the increasing level of vitamin E. Superoxide dismutase and catalase activity were slightly elevated by dietary supplementation of vitamin E. And there was a tendency of higher these enzyme activity of caffeine groups. The activity of glutathione perxidase tended to decrease as dietary vitamin E level increased. But it was raised by caffeine supplementation . Liver glutathione content was not affected by dietary supplementation of vitamin E, but it showed a decreasing tendency in caffeine groups. There was a tendency of more lipid peroxide content of caffeine groups than that of the only vitamin E supplemented group. But the degree of increment of this decreased as dietary vitamin E level increased.

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세심탕(洗心湯)이 뇌조직(腦組織)의 산화작용(酸化作用)에 미치는 영향(影響) (The Antioxidant Effects of Sesimting on the Brain Tissue of Rat)

  • 김성현;이상룡
    • 동의신경정신과학회지
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    • 제8권2호
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    • pp.39-50
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    • 1997
  • This experiment was to investigate the antioxidant effect of Sesimtang(SST) on brain tissues of mouse. The experimental groups were divided into three groups and treated ad follows for 15 days ; Normal group(NC), Vt.E admistrated group(PC), SST administrated Group(SST). After the extracting microsome from brain of mouse, those were measured the amounts of oxidant materials like MDA(malonaldehyde) and $H_2O_2$, then activities of antioxidant enzymes like SOD(superoxide dismutase), catalase, NADPH-cytochrome P-450 reductase. The results were as follows; 1. In TBA reaction to measure the amount of MDA, oxidant material of brain tissue of aged rat, both treated groups showed significant decrease. 2. Hydrogen peroxide formation was showed significant decrease in both treated groups than normal group. 3. Superoxide dismutase activity was increased in both treated groups than normal group, and showed little change in SST administrated group than normal group. 4. Catalase activity was increased in both treated groups than normal group. 5. NADPH-cytochrome P-450 reductase activity was increased in both treated groups than normal group.

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온담탕(溫膽湯)이 뇌조직(腦組織)의 산화작용(酸化作用)에 미치는 영향(影響) (The Antioxidant Effects of ONDAMTANG on the Brain Tissue of Mouse)

  • 정인철;이상룡
    • 동의신경정신과학회지
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    • 제8권2호
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    • pp.51-62
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    • 1997
  • This experiment was done to investigate the antioxidant effect of Ondamtang(ODT) on brain tissues of rats. The experimental groups were divided into three groups and treated as follows for a fifteen days ; Negative control group(NC), Vitamin E admistrated group(PC), ODT administrated Group(ODT). After the extracting microsome from brain of rats, those were measured the amounts of Malondiadehyde and Hydrogen peroxide, then activities of antioxidant enzymes like Superoxide dismutase, Catalase and NADPH-cytochrome P-450 reductadse. The results were as follows; 1. In TBA reaction to measure the amount of MDA, oxidant material of brain tissue of rats, the group treated by ODT showed significant decrease. 2. In the formation of Hydrogen peroxide, the group treated by ODT showed no change in comparison with normal group. 3. The activity of SOD in the group treated by ODT showed a little increase in comparison with normal group. 4. The activity of Catalase was increased significantly in the group treated by ODT than normal group. 5. The activity of NADPH-cytochrome P-450 reductase in the group treated by ODT showed a little increase in comparison with normal group. According to the above results, it is suggested that Ondamtang(ODT) has some antioxidant effects on tissues of brain.

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환소단(還少丹) 뇌조직(腦組織)의 산화작용(酸化作用)에 미치는 영향(影響) (The Antioxidant Effects of HWANSODAN on the Brain Tissue of aged Rat)

  • 서원희;이상용
    • 동의신경정신과학회지
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    • 제9궈1호
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    • pp.45-57
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    • 1998
  • The effect of HWANSODAN(HSD), on the level of brain antioxidants was examined in aged rat. The experimental groups were divided into three groups and treated as follows ; normal group(negative control), Vt.E administrated Group(HSD). The purified microsome from brain tissue, those were measired the amounts of oxidant materials like Malonfialdehyde(MDA) and H2O2, then activities of antioxidants enzymes like superoxide dismutase, catalase, NADPH-cytochrome P-450 reductase.The results were as follows;1. In TBA reaction to measure the amount of MDA, HSD group and Vt.E group did not showed signigicant decrease.2. In the formation of Hydrogen peroxide, HSD group and Vt.E group showed a little increase.3. The activity of Superoxide dismutase was increased significantly in HSD group and Vt.E group.4. In the activity of Catalase, Vt.E group was increased significantly and HSD group a little increased. 5. The activity of NADPH-cytochrome P-450 reductase in the HSD group and Vt.E group showed significantly increase.According to the above results, it is suggested that HWANSODAN(HSD) has some antioxidant effects on the tissue of brain.

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일차 배양한 흰쥐의 간세포에서 사염화탄소로 인한 독성에 미치는 비테인의 효과 (Effects of Betaine on the $CCI_4$-Induced Toxicity in Primary Cultured Rat Hepatocytes)

  • 김선여;김홍표;이미경;김승희;문애리;한형미;허훈;김영중
    • 약학회지
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    • 제37권5호
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    • pp.499-503
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    • 1993
  • Betaine, a major component of Lycii Fructus, was evaluated for its anti-hepatotoxic activity on carbon tetrachloride-induced hepatotoxicity in primary cultured rat hepatocytes. Betaine was found to attenuate carbon tetrachloride-induced hepatotoxicity both morphologically and biochemically. Typical hepatocyte necrosis due to carbon tetrachloride seemed to be reduced by 50 to 500 $\mu{M}$ of betaine under microscopical observation. The value of glutamic pyruvic transaminase released from the hepatocytes into the medium significantly decreased as betaine concentration increased. Betaine also significantly elevated the reduced activities of some enzymes, cytochrome P-450, 7-ethoxycoumarin-0-deethylase and glutathione-S-transferase, involved in xenobiotic metabolism due to carbon tetrachloride-induced hepatotoxicity. These results demonstrate a possible hepato-protective role of betaine against fatty liver that could be easily induced by carbon tetrachloride.

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사염화탄소에 의하여 유발된 흰쥐의 간 독성에 미치는 비테인의 효과 (The Effect of Betaine on the $CCI_4$-Induced Hepatotoxicity in Rats)

  • 김선여;김홍표;이미경;변순정;김승희;문애리;한형미;허훈;김영중
    • 약학회지
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    • 제37권5호
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    • pp.538-543
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    • 1993
  • Effects of betaine, a major component of Lycii Fructus, on carbon tetrachloride intoxicated rats were evaluated. Histological studies showed that betaine had improved the typical necrosis around centrilobular area in liver tissue due to the carbon tetrachloride intoxication. Betaine, whether it was administrated simultaneously or prior to carbon tetrachloride, prevented or retarded the elevation of liver-weight/body-weight ratio due to the carbon tetrachloride intoxication. Betaine also significantly elevated the reduced activities of some enzymes, cytochrome P-450, 7-ethoxycoumarin-0-deethylase and glutathione-S-transferase, involved in xenobiotic metabolism due to carbon tetrachloride intoxication. These results demonstrate a possible hepato-protective role of betaine against fatty liver that could be easily induced by carbon tetrachloride in rat.

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Water Extract of Ash Tree (Fraxinus rhynchophylla) Leaves Protects against Paracetamol-Induced Oxidative Damages in Mice

  • Jeon, Jeong-Ryae
    • Food Science and Biotechnology
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    • 제15권4호
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    • pp.612-616
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    • 2006
  • The protective effect of water extract of ash tree leaves (ALE) against oxidative damages was investigated in paracetamol-induced BALB/c mice. Biochemical analysis of anti-oxidative enzymes, immunoblot analyses of hepatic cytochrome P450 2El (CYP2E1), and the gene expression of tumor necrosis factor (TNF-${\alpha}$) were examined to determine the extract's protective effect and its possible mechanisms. BALB/c mice were divided into three groups: normal, paracetamol-administered, and ALE-pretreated groups. A single dose of paracetamol led to a marked increase in lipid peroxidation as measured by malondialdehyde (MDA). This was associated with a significant reduction in the hepatic antioxidant system, e.g., glutathione (GSH). Paracetamol administration also significantly elevated the expression of CYP2E1, according to immunoblot analysis, and of TNF-${\alpha}$ mRNA in liver. However, ALE pretreatment prior to the administration of paracetamol significantly decreased hepatic MDA levels. ALE restored hepatic glutathione and catalase levels and suppressed the expression of CYP2E1 and TNF-${\alpha}$ observed in inflammatory tissues. Moreover, ALE restored mitochondrial ATP content depleted by the drug administration. These results show that the extract of ash tree leaves protects against paracetamol-induced oxidative damages by blocking oxidative stress and CYP2E1-mediated paracetamol bioactivation.