• 제목/요약/키워드: Metabolizing Enzyme

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해조류 곰피로부터 분리한 Phloroglucinol이 흰쥐의 아세트아미노펜 대사효소활성에 미치는 영향 (Effects of Phloroglucinol Isolated from Ecklonia stolonifera on the Acetaminophen-Metabolizing Enzyme System in Rat)

  • 박종철;허종문;박주권;김현주;전순실;최재수;최종원
    • 한국식품영양과학회지
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    • 제29권3호
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    • pp.448-452
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    • 2000
  • 실험동물에서 곰피로부터 분리한 phlorglucinol은 acetaminophen의 투여로 현저히 증가된 간조직에 있어서 지질과선화의 함량을 억제하였다. Acetaminophen 투여에 따른 간 cytochrome P-450, aminopyrine N-deme-thylase 및 aniline hydroxylase 활성변동은 관찰할 수 없었다. 곰피 성분 투여군은 glutathione S-transferase의 활성에서는 대조군의 수준에는 미치지 않으나 효소의 활성이 acetaminophen 단독 투여군보다 현저히 증가되었다. 그리고 간조직중 glutathione의 함량은 phlorglucionl을 전처리군에서 acetaminophen 단독 투여군보다 증가되었다. Glutathione reductase 활성에서는 acetaminophen 투여군은 대조군보다 활성이 감소되었으며, 성분으로 전처리한 군은 acetaminophen 단독 투여군보다 증가 되었다. 따라서 곰피에서 분리한 페놀성화합물인 phloroglucinol은 acetaminophen 투여로 증가되던 지질과 산화함량을 감소시키며, acetaminophen 대사효소활성에서는 glutathione S-transferase의 활성이 증가되어 acetaminophen 의 대사를 촉진시키는 것으로 추정된다.

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천련자 추출물이 간기능(肝機能)에 미치는 영향(影響)(I) -천련자의 분획이 약물대사효소계 및 담즙분비에 미치는 영향- (The Effects of Meliae toosendan Fructus on Liver Function (I) -Effects of Each Fractions from Meliae toosendan Fructus on Drug Metabolism Enzyme System and Bile Secretion-)

  • 김부생;최종원;이정규
    • 생약학회지
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    • 제24권1호
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    • pp.63-68
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    • 1993
  • Meliae toosendan Fructus is the fruit of Melia toosendan $S_{IEB}$. et $Z_{UCC}$. (Meliaceae), which is written in oriental terminology as clearing heat and drying dampness, and also explained using liver, stomach and small intestine for channels entered. Among the five fractions prepared from methanol whole extractive of the herb, the chloroform fraction which suggests the presence of triterpenoid, flavonoid and alkaloid stimulated the activities of drug metabolizing enzymes and bile secretion and lowered the serum transaminase activities of liver damaged by carbon tetrachloride.

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THE EFFECTS OF ALTERING THE HEPATIC DRUG METABOLIZING ENZYME ACTIVITY ON THE ACUTE TOXICITY OF DIETHYL-4-NITROPHENYL PHOSPHOROTHIOATE (PARATHION) IN FEMALE RATS1.

  • Kim, Young-Chul;Park, Jae-Hwa;Lim, Hye-Kyung
    • Toxicological Research
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    • 제4권2호
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    • pp.107-115
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    • 1988
  • The effects of altering the hepatic mixed-function oxidase(MFO) activities on the acute toxicity of parathion were examined in female rats. Phenobarbital sodium pretreatment (50mg/kg/day, i.p.) for 4 consecutive days has resulted in significant decreases in the toxicity of parathion (2 or 4 mg/kg, i.p.) as determined by lethality and cholinesterase activities wheras the toxicity arising from a single dose of CCl4(2 mmol/kg, i.p.) 24 hr prior to parathion challenge was potentiated.

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Protective Effect of Diallyl Disulfide on Ethacrynic Acid-Inducted Toxicity in Mice

  • Huh, Keun;Lee, Sang-Il;Song, Jae-Woong
    • Archives of Pharmacal Research
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    • 제10권3호
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    • pp.149-152
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    • 1987
  • The present work was undertaken to investigate the effect of diallyl disulfide on ethacrynic acid toxicity. Ethacrynic acid-induced morality and formation of lipid peroxide were inhibited by diallyl disulfide. Furthermore, decreasing effect of glutathione S-transferase and glutathione level in the liver by ethacrynic acid were reduced by diallyl disulfide. These results suggested that the inducing effect of diallyl disulfide on the ethacrynic acid metabolizing enzyme, glutathione S-transferase, is believed to be a possible detoxication mechanism for the ethacrynic acid toxicity in mice.

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Alcohol 섭취 쥐에서 Alchol 대사효소계에 미치는 복어추출물의 효과 (Effect of Puffer Fish Extract on the Hepatic Alcohol Metabolizing Enzyme System in Alcohol-Treated Rat)

  • 김동훈;김동수;최종원
    • 한국식품영양과학회지
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    • 제23권2호
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    • pp.181-186
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    • 1994
  • The present study was undertaken to clarify the effect of Puffer fish skin extract (PF) on the hepatic alcohol metabolism in rats. It was observed that alcohol concentration in blood had been markedly decreased by the pretreatment of PF for two weeks. Activities of alcohol dehydrogenase (ADH) and microsomal ethanol-oxidizing system (MEOS) were significantly incrased (more than 20% of control) by pretreatment of PF for two weeks and acute alcohol intoxication (5 g/kg) on final day. When rats were fed with subacute toxic state by alcohol (25v/v % , once a day for six weeks), activities of ADH and MEOS were significantly increased by additional treatments of PF for final two weeks. But the catalase activity was not affected by any of both case. And also activities of ADH and MEOS in vitro were not changed . These results suggest that PF treatemnt prompted the recovery from alcohol intoxication.

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EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON CYTOCHROME P-450-DEPENDENT DRUG METABOLISM IN PRIMARY MOUSE HEPATOCYTES CULTURES AND MOUSE HEPATOMA CELLS

  • Jung, Hyun-Ho;Jeong, Hye-Gwang;Lee, Michael
    • Toxicological Research
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    • 제9권2호
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    • pp.177-186
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    • 1993
  • Previous results from several laboratories have demonstrated that tumor necrosis factor-alpha (TNFalpha) depressed cytochrome P-450 (P-450)-dependent drug metabolism in vivo. However, there is some debate whether the action of TNFalpha is mediated by its direct effects on hepatocytes, or is indirectly mediated through the release of other mediators like IL-1 from macrophages. In the present studies, we investigated the effects of TNFalpha on P-450-dependent drug metabolizing enzyme as measured by 7-ethoxyresorufin O-deethylase (EROD) activity.

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Induction of Quinone Reductase by Obtusafuran from Dalbergiae Lignum

  • Yin, Hu-Quan;Oh, Seon-Hee;Kim, Youn-Chul;Sohn, Dong-Hwan;Lee, Byung-Hoon
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.161.1-161.1
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    • 2003
  • NAD(P)H:quinone oxidoreductase (quinone reductase: QR: EC1.6.99.2), a cytosolic FAD-containing flavoprotein, form one of the important component of the phase II drug-metabolizing enzyme systems. It is found in all mammalian species tested and is expressed in many organs including the liver. QR catalyses two-electron reduction of qui nones to hydroquinones thereby suppresses the formation of superoxide anion radical. (omitted)

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Cytochrome P-450 3A4 proximal promoter activity by histone deacetylase inhibitor in HepG2 cell.

  • Kim, Ja-Young;Ahn, Mee-Ryung;Sheen, Yhun-Yhong
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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    • pp.120.2-120.2
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    • 2003
  • Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this is detoxification and metabolizing more than 50% clinical drugs in use. Expression of CYP3A4 is transciptionally regulated by the Pregnenolone X receptor (PXR), of which human form is Steroid and Xenobiotics receptor (SXR). SXR is activated by wide range of endogenous and exogenous compounds, and then induces CYP3A4 gene expression. In the previous study, it has been known that proximal promoter (-864 to +64) does not response to chemical inducers such as pregnenolone 16a-carbonitrile (PCN), Rifampicin, Estrogen in terms of transcription of CYP 3A4 in cultured cells. (omitted)

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수종 지혈 한약물이 Cytochrome P450 3A4 활성에 미치는 영향 (Influence of Five Herbal Medicines on Cytochrome P450 3A4 Drug-Metabolizing Enzymes in Human Liver Microsomes)

  • 황진우;고재언;고호연;최유경;박종형;전찬용
    • 대한한방내과학회지
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    • 제29권4호
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    • pp.846-855
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    • 2008
  • Objects : The aim of this study was to investigate the influence of five herbal medicines on cytochrome P450 3A4 drug-metabolizing enzymes in human liver microsomes. Methods : To use human liver microsomes, an extract of five herbal medicines, which are Artemisia princeps Pampan, Sophora jeponica Linne, Panax notoginseng F. H. Chen, Lithospermum Erythrorhizon Sieb., and Cirsium maackii Maxim, which together are called Jihyulyak(止血藥, drugs for arresting bleeding, hemostatics), was co-incubated and measured for relative enzyme activity in incubation condition compared to ketoconazole, a representative inhibitor of CYP 3A4. Results : We showed that all five of the traditional herbal medicines had no inhibition effect of CYP 3A4 at 10, 20, 30, 40, and $50{\mu}g/ml$ doses in human liver microsomes, although Sophora japonica Linne(SJL) showed a little inhibition at about 81% inhibition rate of control. However, this result is not enough to prove that SJL has a CYP 3A4 inhibition effect. Moreover, we can't make sure that those rates had significant induction effect on CYP 3A4. Conclusions : The result of this study could support that those herbal medicines are safer than chemical drugs, even if this is the basic step to prove that result.

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CCl4전처치한 흰쥐에 Cyclohexane 투여가 간손상에 미치는 영향 (Effect of Cyclohexane Treatment on the Liver Damage in CCl4-Pretreated Rats)

  • 윤종국;김현희
    • Toxicological Research
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    • 제19권2호
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    • pp.105-114
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    • 2003
  • TO evaluate an effect of cyclohexane treatment on the degree of liver damage, rats were induced liver damage with 10 or 17 times $CCl_4$ injection (0.1 m1/100 g body wt., 50% $CCl_4$ dis-solved in olive oil) at intervals of every other day. Cyclohexane (1.56 g/kg body wt., i.p.) was administrated to the animals at 48 hours after the last pretreatment of $CCl_4$ . Rats were sacrificed at 4 hours after injection of cyclohexane. On the basis of histopathological findings, liver weight/body weight (LW/ BW, %), activities of serum alanine aminotransferase (ALT), xanthine oxidase (XO) and akaline phosphatase (ALP), and contents of liver protein and manlondialdehyde (MDA), $CCl_4$ -pretreatment induced liver damage. And $CCl_4$ 17 times treated group showed more severe liver damage than $CCl_4$ 10 times treated group. Administration of one dose of cyclohexane to $CCl_4$ 10 times treated animals resulted in the enhanced liver damage; liver necrosis with proliferation of fibroblast and bile duct abnormality, and increase in hepatic MDA content and the activities of serum ALP and ALT, But the enhanced liver damage was not found in $CCl_4$ 17 times treated animals. Serum cyclohexanone concentrations at 4 or 8 hours after injection of cyclohexane were higher in all liver damaged groups than normal group and were somewhat higher In $CCl_4$ 17 times treated animals than $CCl_4$ 10 times treated ones. Among the oxygen free radical metabolizing enzymes, hepatic cytochrome P45O dependent aniline hydroxylase (CYPdAH) activity in cyclohexane metabolizing enzyme system was meaningfully increased by the injection of cyclohexane to the liver damaged rats, with increased Vmax and high affinity to aniline. LW/BW (%) and activities of serum XO and ALT were more significantly increased in liver damaged groups than normal group by administration of cyclohexanone. In conclusion, it is assumed that an enhancement of liver damage by injection of one dose of cyclohexane to liver damaged animals might be caused by oxygen free radicals and cyclohexanone.