• 제목/요약/키워드: CYP2E1

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Effect of Fermented Cucumber Beverage on Ethanol Metabolism and Antioxidant Activity in Ethanol-treated Rats (오이 발효음료가 만성적으로 에탄올을 급여한 흰쥐의 에탄올 대사와 항산화방어계에 미치는 영향)

  • Lee, Hae-In;Seo, Kwon-Il;Lee, Jin;Lee, Jeom-Sook;Hong, Sung-Min;Lee, Ju-Hye;Kim, Myung-Joo;Lee, Mi-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.8
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    • pp.1099-1106
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    • 2011
  • Cucumber fermentation has been used as a means of preservation. This study was performed to investigate the effects of fermented cucumber beverage (CF) containing beneficial materials for an ethanol hangover based on Hovenia dulcis (SKM) on ethanol-induced hepatotoxicity. Male Sprague-Dawley rats were randomly divided into three groups: ethanol control, ethanol plus SKM, and ethanol plus CF+SKM. SKM or CF+SKM was orally administered at a dose of 7 mL/kg body weight once per day for 5 weeks. Control rats were given an equal amount of water. CF+SKM significantly lowered plasma ethanol levels, whereas SKM tended to decrease the levels compared to the control. Both SKM and CF+SKM significantly lowered the plasma acetaldehyde levels and serum transaminase activities compared to those in the control. SKM and CF+SKM did not affect hepatic alcohol dehydrogenase activity; however, it significantly inhibited cytochrome P450 2E1 (CYP2E1) activity. Hepatic aldehyde dehydrogenase (ALDH) activity was significantly higher in the SKM and CF+SKM groups than that in the control group. Plasma acetaldehyde concentration was significantly correlated with hepatic CYP2E1 (r=0.566, p<0.01) activity and ALDH (r=-0.564, p<0.01) activity. Hepatic superoxide dismutase and catalase activities as well as glutathione content increased with the SKM and CF+SKM administration, whereas lipid peroxide content decreased significantly. Furthermore, SKM and CF+SKM lowered plasma and hepatic lipid content and lipid droplets compared to those in the control group. These results indicate that SKM and CF+SKM exhibit hepatoprotective properties partly by inhibiting CYP2E1 activity, enhancing ALDH activity and stimulating the antioxidant defense systems in ethanol-treated rats.

Inhibitory Effects of Medicinal Herbs on Cytochrome P450 Drug Metabolizing Enzymes (생약추출물의 Cytochrome P450 약물대사 효소계 저해활성)

  • Jeong, Hye-Gwang;You, Ho-Jin;Chang, Young-Su;Park, Sung-Jun;Moon, Young-Hee;Woo, Eun-Rhan
    • Korean Journal of Pharmacognosy
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    • v.33 no.1 s.128
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    • pp.35-41
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    • 2002
  • The MeOH ext., $CH_2Cl_2$ Frac., EtOAc Frac., n-BuOH Frac., and $H_2O$ Frac. of 23 Korean medicinal herbs were prepared and were tested the inhibitory effects on Cytochrome P450 (Cyp) 1A1/2, 2B1/2, 2E1. Among the tested samples, the extracts of Selaginella tamariscina, Euonymus alatus, Salvia miltiorhiza, Angelica acutiloba, Rheum palmatum, Paeonia moutan, Scutellaria barbata, Tribulus terrestris, Hedyotis diffusa, Curcuma zedoaria, Rehmania glutinosa, Trogopterus xanthipes, Melandryum firmum, Achyranthes bidentata, Leonurus sibricus, Panax ginseng, Paeonia lactiflora, Poncirus trifoliata, Cnidium officinale, Cyperus rotundus, Corydalis ternata showed significant inhibitory effects on Cyp 1A1/2, 2B1/2, 2E1. The $IC_{50}$ values of those extracts were found to be below $50\;{\mu}g/ml$.

Evaluation of Risk Factors for Nasopharyngeal Carcinoma in a High-risk Area of India, the Northeastern Region

  • Lourembam, Deepak Singh;Singh, Asem Robinson;Sharma, T. Dhaneshor;Singh, Th Sudheeranjan;Singh, Thiyam Ramsing;Singh, Lisam Shanjukumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4927-4935
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    • 2015
  • Northeastern India is a major nasopharyngeal carcinoma (NPC) high risk-area although the rest of the country has very low incidence. A case-control study of 105 NPC cases and 115 controls was conducted to identify the potential risk factors for NPC development in this region. Information was collected by interviewer about socio-demographic characteristics, cigarette smoking, alcohol consumption, dietary history, occupational history, and a family history of cancer. Epstein-Barr viral load was assayed from the blood DNA by real time PCR. Associations between GSTs genotypes, cytochrome P450 family including CYP1A1, CYP2E1 and CYP2A6 polymorphisms and susceptibility to relationship between the diseases were studied using PCR-RFLP assay. Results indicate that Epstein-Barr virus load was significantly higher in patients compared to controls (p<0.0001). Furthermore, concentration of blood EBV-DNA was significantly higher in advanced stage disease (Stage III and IV) than in early stage disease (Stage I and II) (p<0.05). Presence of CYP2A6 variants that reduced the enzyme activity was significantly less frequent in cases than controls. Smoked meat consumption, exposure to smoke, living in poorly ventilated house and alcohol consumption were associated with NPC development among the population of Northeastern India. Thus, overall our study revealed that EBV viral load and genetic polymorphism of CYP2A6 along with living practices which include smoked meat consumption, exposure to smoke, living in poorly ventilated houses and alcohol consumption are the potential risk factors of NPC in north eastern region of India. Understanding of the risk factors and their role in the etiology of NPC are helpful forpreventive measures and screening.

The Protective Effects of Garlic against Carbon tetrachloride-induced Hepatotoxicity (마늘에 의한 사염화탄소 간독성의 보호 효과)

  • Lee, Jong-Moon;Park, Jung-Duck;Hong, Yeon-Pyo;Choi, Byung-Sun
    • Journal of Preventive Medicine and Public Health
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    • v.35 no.3
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    • pp.221-228
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    • 2002
  • Objectives : The purpose of this study was to find the protective effects of garlic on the halogenated hydrocarbon induced hepatotoxicities, and the possible protection mechanisms involved. Methods : Male Sprague-Dawley rats received garlic (0.5%) or regular diet, for 4 weeks. This was followed by a single dose of corn oil (the controls), carbon tetrachloride (400mg/kg body weight) and trichloroethylene (2,000mg/kg body weight) being administered to each diet group. Blood samples were collected 24 hours fellowing the administration, and the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALD activities measured. The liver samples were studied for their cytochrome P450 and CYP2E1 contents, lipid peroxidation and histopathology. Results : rho results for the group receiving the 9.5% garlic diet showed a slight decrease of CYP2E1 expression compared with the regular diet group. Carbon tetrachloride was significantly decreased the CYP2E1 contents in both the regular and garlic diet groups, but the trichloroethylene remained unchanged. Garlic did not decrease the lipid peroxidation of the liver in the control group, but attenuated the increase of lipid peroxidation caused by carbon tetrachloride. Garlic attenuated the increase of both the serum AST and ALT activities caused by carbon tetrachloride. The histopathelogical observations also showed that garlic attenuated centrilobular necrosis and vacuolar degenerative changes significantly in the carbon tetrachloride treated group. Conclusions : The results indicate that garlic attenuates the carbon tetrachloride-induced hepatotoxicity, through the prevention of the metabolic activation and lipid peroxidation.

Histone deacetylation effects of the CYP1A1 promoter activity, proliferation and apoptosis of cells in hepatic, prostate and breast cancer cells

  • K. N. Min;K. E. Joung;M. J. Cho;J. Y. An;Kim, D. K.;Y. Y. Sheen
    • Proceedings of the Korea Society of Environmental Toocicology Conference
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    • 2003.10a
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    • pp.181-181
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    • 2003
  • We have studied the mechanism of action of TCDD on CYP1A1 promoter activity in both Hepa Ⅰ and MCF-7 cells using transient transfection system with p1A1-Luc reporter gene. When HDAC inhibitors, such as trichostatin A, HC toxin and a novel HDAC inhibitor, IN2001 were cotreated with TCDD to the cells transfected with plAt-Luc reporter gene, the basal promoter activity of CYP1A1 was increased by HBAC inhibitors. Also, in MCF-7 human breast cancer cells, HDAC inhibitors, such as IN2001 and trichostatin A increased the basal activity of CYP1A1 promoter but TCDD stimulated CYP1A1 promoter activity was not changed by HDAC inhibitors. And, in stably-transfected Hepa Ⅰ cells with p1A1-Luc, HDAC inhibitors increased the basal promoter activity only Also, we have investigated the effects of HDAC inhibitors on the human breast and prostate cancer cells in terms of cell proliferation and apoptosis based on SRB assay. IN2001 as well as trichostatin A inhibited the MCF-7, MDA-MB-231, MDA-MB-468, T47D, ZR75-1, PC3 cell growth dose-dependently. The growth inhibition of these cells with HDAC inhibitors was associated with profound morphological change, which suggests the HDAC inhibitors induced apoptosis of cells. The result of cell cycle analysis after 24h exposure of IN2001 showed G2/M cell cycle arrest in MCF-7 cells and apoptosis in T47D and MDA-MB-231 cells.

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Protective Effect Naringin on Carbon Tetrachloride Induced Hepatic Injury in Mice (나린진(Naringin)의 $CCl_4$에 의한 급성 간독성 보호효과)

  • Chae, Soo-Chul;Kho, Eun-Gyeong;Choi, Seung-Hyun;Ryu, Geun-Chang
    • Environmental Analysis Health and Toxicology
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    • v.23 no.4
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    • pp.325-335
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    • 2008
  • The protective effects of the Naringin, on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with Naringin prior to the administration of $CCl_4$ significantly prevented an increase in serum alanine, aspartate aminotransferase activity and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with Naringin also significantly prevented the depletion of glutathione (GSH) content in the livers of $CCl_4$-induced mice. However, reduced hepatic glutathione levels was unaffected by treatment with Naringin alone. In addition, Naringin prevented $CCl_4$-induced apoptosis and necrosis, as indicated by a liver DNA laddering. To determine whether caspase-8,-3 pathway involved in $CCl_4$-induced acute liver injury, caspase-8, -3 activities were tested by ELISA. Naringin attenuated $CCl_4$induced caspase-8, -3 activities in mouse livers. $CCl_4$-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic study. The effects of Naringin on the cytochrome P450 (CYP) 2E1, the major isozyme involved in $CCl_4$ were also investigated. Treatment of mice with Naringin resulted in a significant decrease of the CYP2E1-dependent hydroxyl at ion and aniline in a dose-dependent manner. These findings suggest that protective effects of Naringin against the $CCl_4$-induced hepatotoxicity may be due to its ability to block CYP2E1-mediated $CCl_4$ bioactivation and that is also protects against caspase-8, -3 pathway mediated apoptosis.

Time-dependent Effects of Bisphenol Analogs on Ecdysteroid Pathway Related Genes in the Brackish Water Flea Diaphanosoma celebensis (Bisphenol 구조 유사체가 기수산 물벼룩 Ecdysteroid 경로에 미치는 영향)

  • In, Soyeon;Lee, Young-Mi
    • Journal of Marine Life Science
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    • v.6 no.2
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    • pp.73-79
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    • 2021
  • Bisphenol A is a representative endocrine disruptor and continuously detected in aquatic environment due to wide use, resulting in adverse effects on growth, development, and reproduction in diverse organisms as well as human. Structural analogs have been developed to substitute BPA are also suspected to have endocrine disrupting effects. In the present study, the time-dependent expression patterns of ecdysteroid synthesis (nvd, cyp314a1), receptors (EcRA, EcRB, USP, ERR), and downstream signaling pathway - related genes (HR3, E75, Vtg, VtgR) were investigated using quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) in the brackish water flea Diaphanosoma celebensis exposed to Bisphenol analogs (BPs; BPA, BPF, and BPS) for 6, 12, and 24 h. As results, the expression of nvd, cyp314a1, EcRs, USP, ERR and E75 mRNA was upregulated at 6 h exposure to BPF, which is earlier than BPA and BPS (12 h). On the other hand, HR3, E75 and VtgR mRNA levels were elevated at 6 h earlier at BPS and BPF than at BPA (12 h), but Vtg mRNA level was slightly changed within 24 h. These findings suggest that like BPA, BPF and BPS can also modulate the transcription of ecdysteroid pathway - related genes with different mechanisms, and have a potential as endocrine disruptors. This study will provide a better understanding the molecular mode of action of bisphenols on ecdysteroid pathway in the brackish water flea.

BENZENE INDUCED CHROMOSOME ABERRATIONS AND THE ASSOCIATION WITH GENETIC POLYMORPHISM

  • Kim, Su-Young;Cho, Yoon-Hee;Jung, Eun-Jung;Park, Jung keun;Paek, Do-Myung;Chung, Hai-Won
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.66-66
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    • 2002
  • This study was done to examine the benzene induced chromosomal aberrations and also the influence of genetic polymorphism(GSTM1, GSTT1, GSTP1, NAT2, NQO1, CYP2E1 and CYP1A1) on the chromosomal aberrations. In total, 82 benezene exposed workers and 76 matched controls were examined.(omitted)

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Effects of herbal-aupuncture solution from vitis labrusca root on LPO, RNS and cytochrome P450 (포도근 약침액이 LPO, RNS 및 Cytochrome P450에 미치는 효과)

  • Lim, Seong-Cheorl;Kim, Hyuck;Lee, Hyo-Seung;Park, Won-Hwan;Moon, Jin-Young
    • Korean Journal of Acupuncture
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    • v.24 no.1
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    • pp.161-170
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    • 2007
  • Objectives : In this study, we determinated protective effects of Vitis labrusca Root herbal-acupuncture solution (VLHA) against atherosclerosis and cardiovascular disease induced by oxidative damage and cytochrome P450 (CYP) induction. Methods : Antioxidant capacity of VLHA were evaluated by the ${\beta}-carotene/linoleic$ acid emulsion system and FeCl2-ascorbic acid stimulted lipid peroxidation in rat liver homogenate, respectively. Scavenging effects of VLHA on ONOO- and NO were measured by DHR 123, DAF-2 assay. Furthermore, we measured inhibitory activity of VLHA on CYP 2E1 in rat liver microsome using by Aniline assay. Results : VLHA exhibited potent inhibition rate(74%) on FeCl2-ascorbic acid induced lipid peroxidation, and revealed a strong scavenging effects on ONOO- and NO. In addition, VLHA showed inhibitory effect on CYP 2E1. Conclusions : The present study concludes that our results suggest that VLHA could be used as a good source in the prevention of atherosclerosis and alcoholic liver injury.

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Effects of Xenoestrogens on Gene Expression of Cytochrome P450 Genes in in vitro Cultured Mice Spermatogenic Cells (체외배양 생쥐정소세포에서 합성에스트로겐이 P450 등위효소의 발현에 미치는 영향)

  • Lee, Ho-Joon;Kim, Myo-Kyung;Ko, Duck-Sung;Kim, Kil-Soo;Kang, Hee-Kyoo;Kim, Dong-Hoon
    • Clinical and Experimental Reproductive Medicine
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    • v.28 no.2
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    • pp.131-140
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    • 2001
  • Objective: To know the effects of xenoestrogen on spermatogenesis, we investigated the expression of cytochrome P450s enzymes (CYPscc, $CYP_{17{\alpha}}$, CYP19) and $3{\beta}$-HSD genes involved in steroidogenesis. Methods: Mouse testicular cells were prepared from 15-day-old ICR mice which had only pre-meiotic germ cells by enzyme digestion using collagenase and trypsin. Testicular cells were cultured in DMEM supplemented with FSH (0.1 IU/ml) and 10% FBS or medium with estrogen ($E_2$), bisphenol-A (BPA), octylphenol (OP; $10^{-9},\;10^{-7},\;10^{-6},\;10^{-5},\;10^{-4}M$, respectively) and aroclor 1254 (A1254) known as PCBs for 48 hours. The gene expression of cytochrome P450 enzymes were examined by semi-quantitive RT-PCR. The production of estrogen and testosterone was examined by RIA. Results: As results, expression of CYPscc mRNA was not significantly decreased, but $3{\beta}$-HSD and $CYP_{17{\alpha}}$. mRNA were significantly dose-dependent decreased. And production of testosterone and estrogen were not different except BPA and OP group ($10^{-5}M$). Conclusion: BPA, OP and A1254 might inhibit steroidogenesis by decreasing CYPscc, $3{\beta}$-HSD and $CYP_{17{\alpha}}$. mRNA expression in the mouse testis. These results suggest that BPA, OP and PCBs like as an endocrine disruptors inhibit the productions of steroidogenic enzymes and decrease the production of T and E by negative feedback mechanism. Therefore, these might disrupt steroidogenesis in Leydig cells of testis and would disturb testicular function and subsequently impair spermatogenesis.

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