• Title/Summary/Keyword: cytochrome P450s

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IN VITRO INHIBITION BY TRICYCLIC ANTIDEPRESSANTS OF PHENYTOIN p-HYDROXYLATION: MECHANISTIC APPROACH

  • Park, Ji-Young;Kim, Min-Jung;Shon, Ji-Hong;Shin, Jae-Gook
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.195-195
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    • 2001
  • The inhibitory potentials of TCAs (imipramine, desipramine, amitriptyline, and nortriptyline) on phenytoin p-hydroxylation and probe metabolic pathways of each CYP isoforms were evaluated from incubation studies of human liver microsomes and cDNA-expressed cytochrome P450s in vitro in order to understand the mechanism of drug interaction between TCAs and phenytoin, a substrate of CYP2C9 and CYP2C19. (omitted)

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Protective Effect of Marine Natural Products on the Hepatic Lipid Peroxidation in Acetaminophen-treated Rats (아세트아미노펜 유도 흰쥐에서 수산생물자원 추출물의 in vivo 간보호작용)

  • Choe, Jong-Won;Park, Jong-Cheol
    • YAKHAK HOEJI
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    • v.40 no.5
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    • pp.574-581
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    • 1996
  • The study was initiated to elucidate the protective mechanism by examining in vivo effect of some marine natural products, Styela plicata, Ecklonia stolonifera and Pachymeniopsis elliptica on acetaminophen-induced lipid peroxidation. The methanol extract of S. plicata prevented acetaminophen (800mg/kg, i.p.)-induced hepatotoxicity in rats as evidenced by the decreased formation of lipid peroxide. But the methanol extracts of E. stolonifera and P. elliptica were not affected on the formation of lipid peroxidation. The activities of cytochrome P-450, animopyrine N-demethylase and aniline hydroxylase were not changed by the treatment with S. plicata in comparison with acetaminophen-teated group. In acetaminophen-treated control rats, the glutathione S-transferase activity was decreased markably. However. in S. plicata pretreated group, the effect caused by acetaminophen was markably reduced. A-cetaminophen decreased the level of hepatic, glutathione, which was restored to same degree by S. plicata pretreatment. And activity of ${\gamma}$-glutamylcystein synthetase was not changed by S. plicata pretreatment, but the activity of glutathione reductase was increased significantly.

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Effects of Puffing Red Ginseng Powder on Antioxidant Enzyme Activities in Benzo(α)Pyrene-Treated Mice (팽화홍삼분말이 벤조피렌을 투여한 마우스의 항산화 효소 활성에 미치는 영향)

  • Kim, Hyun-Jeong;Lee, Ki-Dong;Lee, In-Seon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.7
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    • pp.847-852
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    • 2008
  • In order to determine the effects of puffing red ginseng (PRG) powder on the antioxidant enzyme activities of hepatotoxicity in benzo($\alpha$) pyrene[B($\alpha$)P]-treated mice, the mice were divided into 5 groups. The dried red ginseng were prepared by puffing conditions of moisture content 10% and puffing pressure $5\;kgf/cm^2$, and then powdered. PRG powder was injected i.p. once a day for 5 successive days, followed by the administration of B($\alpha$)P treatment on the fifth day. We also evaluated the relationship between lipid peroxidation and PRG powder on oxidative stress. The increased activities of superoxide dismutase, catalase, and glutathione peroxidase observed following B($\alpha$)P-treatment were reduced by the treatment of PRG powder. Whereas the glutathione content and glutathione S-transferase activity depleted by B $\alpha$)P were significantly increased, the B($\alpha$)P-associated elevation of cytochrome P-450 activities and lipid peroxide content were reduced as the result of PRG powder treatment. Especially, PRG powder had higher antioxidant activities than RG powder. These results suggest that puffing red ginseng powder can protect against B($\alpha$)P intoxicification through its antioxidant properties.

Combinatory Effects of Benzene, Toluene and Xylene on the Induction of Rat Liver Microsomal Enzymes and Their Metabolites (흰쥐 간의 microsomal enzymes의 유도에 있어서 benzene, toluene과 xylene의 복합적인 영향과 그들의 대사산물)

  • 김기웅;박상신;김태균;문영한;장성근
    • Toxicological Research
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    • v.12 no.1
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    • pp.9-15
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    • 1996
  • We studied the effects of a single, combined and mixed exposure of benzene, toluene and xylene on the activities of rat liver microsomal AHH, ADH and ALDH, and the excretion of their metabolites in urine. The AHH activities of the rats treated in combination and mixture were slightly higher and/or similar to those rats treated with single solvent, while the reverse effects were observed for ADH and ALDH. Similar effects were observed when the metabolites were examined in urine (p < 0.01). These results suggest that each solvent might interJkre the induction and action of ADH and ALDH, and decrease the excretion of their metabolites into urine.

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Cadmium Toxicity Monitoring Using Stress Related Gene Expressions in Caenorhabditis elegans

  • Roh, Ji-Yeon;Park, Sun-Young;Choi, Jin-Hee
    • Molecular & Cellular Toxicology
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    • v.2 no.1
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    • pp.54-59
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    • 2006
  • The toxicity of cadmium on Caenorhabditis elegans was investigated to identify sensitive biomarkers for environmental monitoring and risk assessment. Stress-related gene expression were estimated as toxic endpoints Cadmium exposure led to an increase in the expression of most of the genes tested. The degree of increase was more significant in heat shock protein-16.1, metallothionein-2, cytochrome p450 family protein 35A2, glutathione S-transferase-4, superoxide dismutase-1, catalase-2, C. elegans p53-like protein-1, and apoptosis enhancer-1 than in other genes. The overall results indicate that the stress-related gene expressions of C. elegans have considerable potential as sensitive biomarkers for cadmium toxicity monitoring and risk assessment.

Mechanism and Effect of Corydalis ternata on the $CCl_4$-Induced$ Hepatotoxicity (사염화탄소에 의한 간손상에 미치는 현호색의 효과 및 그 기전)

  • 서인옥;정춘식;정기화
    • Journal of Food Hygiene and Safety
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    • v.15 no.3
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    • pp.226-234
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    • 2000
  • Protective effect of Corydalis ternata against the carbon tetrachloride-induced toxicity was investigated. Carbon tetrachloride($CCl_4$) induces hepatotoxicity due to the reactive free radical(CCl$_3$ . ) generated by cytochrome P-450 enzyme. We examined effects of hexane, chloroform, butanol and water fractions prepared from the Corydalis ternata methanol extract. Rats were treated with those for 3 days, and liver microsomes and cytosols were prepared at 24 hour after last treatment. Hepatoprotective activity of the water fraction was higher than that of other fractions. To examine mechanism of the hepatoprotective effect of Corydalis ternuta, we measured contents of malondialdehyde(MDA), cytochrome P46O(CYP), glutathione, calcium as well as the activities of NADPH-CYP reductase, glutathione S-transferase(GST), superoxide dismutase(SOD), glutathione peroxidase(GPX) and catalase. The fraction inhibited production of MDA, content of CYP and calcium in liver of water fractions - treated rats as compared with those of CCl4-treated rats. The GST activity was increased. We speculate that the O2 radical scavenging activities of the water fraction might play a key role in the mechanism opposing the progression of $CCl_4$-induced hepatotoxicity, but the activities of SOD, GPX, CAT were decreased. These results suggest that the mechanism might be mainly due to the decrease of CYP contents, act as calcium channel blocker and increase of GST activity rather than $O_2$ radical scavenging activities.

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Screening for inhibitory effect on nine CYP isoforms by 20 herbal medications (고속 스크리닝 기법을 이용한 한약제제의 cytochrome P45O 저해능 탐색)

  • Kim, Hyun-Mi;Liu, Kwang-Hyeon
    • Journal of Life Science
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    • v.17 no.3 s.83
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    • pp.334-339
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    • 2007
  • We evaluated the potential of 20 herbal medications (HMs), commonly used in Korea, to inhibit the catalytic activities of several cytochrome P450 (CYP) isoforms. The abilities of 500 ${\mu}g/ml$ of aqueous extracts of 20 HMs to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), rosiglitazone hydroxylation (CYP2C8), tolbutamide 4-methylhydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The HMs Woohwangcheongsimwon suspension and Hwanglyeonhaedok-Tang strongly inhibited CYP2B6 and CYP2D6 isoform activity, respectively. These results suggest that some of the HMs used in Korea have potential to inhibit CYP isoforms in vitro. Although the plasma concentrations of the active constituents of the HMs were not determined, some herbs could cause clinically significant interactions because the usual doses of those individual herbs are several grams of freeze-dried extracts.

Protective Effect of Curcumin and Aqueous Extract of Onchengyeum on CCI4-induced Hepatotoxicity

  • SEUNG Keum Ran;JUNG Ki Hwa
    • Biomolecules & Therapeutics
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    • v.13 no.4
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    • pp.232-239
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    • 2005
  • An aqueous extract of oriental herbal composition named Onchengyeum and curcumin, an antioxidant isolated from turmeric (Curcuma Zonga L.) reduced hepatotoxicity induced by carbon tetrachloride ($CCI_4$). Improved liver function was observed by measuring the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine (CRE), total cholesterol (T-CHO), triglyceride (TG), low density lipoprotein cholesterol (LDL-CHO), high density lipoprotein cholesterol (HDL-CHO), total protein (TP), albumin (ALB) and total bilirubin (BIL) in serum. Hepatic parameters monitored were levels of cholesterol (CHO), triglyceride (TG), and malondialdehyde (MDA) and activities of cytochrome P450 (CYP), NADPH-CYP reductase, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx). The histopathological examination showed that the treatment of Onchengyeum and curcumin relieved the ballooning degeneration of hepatocytes which had been generated by $CCI_4$. The results suggested that hepatoprotective effects of Onchengyeum and curcumin possibly are due to their promising antioxidative activity.

Protective Effect of Sachungwhan against CCl4-induced Hepatotoxicity

  • Koo, Ja-Young;Jung, Ki-Hwa
    • Biomolecules & Therapeutics
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    • v.14 no.4
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    • pp.207-215
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    • 2006
  • Sachungwhan reduced hepatotoxicity induced by carbon tetrachloride($CCl_4$). Improved liver function was observed by measuring the activities of aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), blood urea nitrogen(BUN), creatinine(CRE), total cholesterol(TCHO), triglyceride(TG), low density lipoprotein cholesterol(LDL-CHO), high density lipoprotein cholesterol(HDL-CHO), total protein(TP), albumin(ALB) and total bilirubin(BIL) in serum. Hepatic parameters monitored were levels of cholesterol(CHO), triglyceride(TG), malondialdehyde(MDA), content of cytochrome P450(CYP), level of glutathione(GSH), and activities of NADPH-CYP reductase, superoxide dismutase(SOD), catalase(CAT), glutathione S-transferase(GST), glutathione reductase(GR), glutathione peroxidase(GPx). The histopathological examination showed that the treatment of Sachungwhan relieved the ballooning degeneration of hepatocytes which had been generated by $CCl_4$. The results suggested that hepatoprotective effects of Sachungwhan possibly are due to their promising antioxidative activity.

The Modulation of Squamous Cell Differentiation by Retinoids in Human Squamous Cell Carcinoma Xenografts (Nude Mouse 에 이종이식한 두경부 편평상피세포암의 분화에 대한 Retinoids의 작용)

  • Kim, Sang-Yoon;Yoo, Seung-Joo;Yoo, Keun-Sik;Joo, Joon-Bum;Choi, Doo-Yung;Nam, Soon-Yuhl
    • Korean Journal of Bronchoesophagology
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    • v.5 no.2
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    • pp.119-126
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    • 1999
  • Objectives : To analyze the effect of retinoids on the differentiation in HNSCC xenografts. Materials and Methods : RA (20mg/kg) or 13-cis-RA (60mg/kg) was orally administered once in a day for 30 days in the xenograft model we prepared using athymic nude mice with AMCHN-4 and -6. We carried out H & E staining and immunohistochemical staining with the monoclonal antibody against involucrin and cytokeratin 10. Results : Both RA and 13-cis-RA were found to suppress the differentiation of AMC-HN-4. Interestingly, RA enhanced the differentiation of AMC-HN-6, although 13-cis RA did not exhibit any effect on the differentiation. These results suggest that in vivo effect of retinoids on the HNSCC growth and differentiation might be various. Retinoids-induced P450 in AMC-HN-6 might be one of the mechanisms to explain the reason why the retinoids exhibit various functions in the HNSCC.

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