• Title/Summary/Keyword: CYP1A2

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PAH regualtion of CYP1 gene in MCF-7 & ZR-75-1 human breast cancer cells

  • Min, Kyung-Nan;Kim, Ja-Young;Kang, So-Hee;Seo, Mi-Jung;Sheen, Yhun-Yhong
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.182.2-183
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    • 2003
  • Recent industrial society has human widely exposed to PAHs that are comming from the incomplete combustion of organic material as widerspread environmetal contaminants. Biological activities of PAHs are not known although PAHs are considered as carcinogens. The mechanism of action of PAHs has been studied extensively, however it is not clear how PAHs turn on CYP1A1 in human breast cancer. (omitted)

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Comparison of Hsp90 and CYP1A Expression Patterns by Water Temperature Stress in Atlantic Salmon (Salmo salar) (대서양 연어(Salmo salar)의 수온 스트레스에 의한 Hsp90 및 CYP1A 발현 양상 비교)

  • Kang, Han Seung;Song, Jae-Hee;Kang, Hee Woong
    • Journal of Marine Life Science
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    • v.3 no.2
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    • pp.51-58
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    • 2018
  • Variations in water temperature are known to affect almost every part of fish physiology. The rise in water temperature due to climate change can physically damage fish. This study was conducted to evaluate the health status of the Atlantic salmon (Salmo salar) at high water temperature (20℃) than the optimum water temperature (15℃). Liver tissue exerts important metabolic functions in thermal adaptation. Therefore, liver tissue was used in this study. The evaluation method is to develop the biomarker gene using NGS RNAseq analysis and to examine the expression pattern using RT-qPCR analysis. The NGS RNAseq analysis revealed 1,366 differentially expressed genes, among which 880 genes were increase expressed and 486 genes were decrease expressed. The biomarker genes are such as heat shock protein 90 alpha (Hsp90α), heat shock protein 90 beta (Hsp90β) and cytochrome P450 1A (CYP1A). The selected genes are sensitive to changes in water temperature through NGS RNAseq analysis. Expression patterns of these genes through RT-qPCR were similar to those of NGS RNAseq analysis. The results of this study can be applied to other fish species and it is considered to be useful industrially.

Organosulfur Compounds in Fermented Garlic Extracts and the Effects on Alcohol Induced Cytotoxicity in CYP2E1-Transfected HepG2 Cells (유산균발효마늘의 유기황화합물과 CYP2E1-Transfected HepG2 Cell에서 알코올 유발 세포독성에 미치는 영향)

  • Jung, Eun-Bong;Choi, Ji-Hwi;Yu, Heui-Jong;Kim, Ki-Ho;Lee, Sung-Ku;Hwang, Young-Il;Lee, Seung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.3
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    • pp.342-347
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    • 2013
  • In this study, we investigated changes in the organosulfur compounds of garlic (by fermentation with lactic acid bacteria) and the effects of these fermented garlic extracts on alcohol-induced cytotoxicity in CYP2E1-transfected HepG2 cells. Lactobacillus plantarum has the highest growth rate in a garlic medium and the S-allyl-L-cysteine (SAC) in fermented garlic extracts with Lactobacillus plantarum and Pediococcus pentosaceus were significantly higher compared to other lactic acid bacteria strains (p<0.05). The SAC, S-ethyl cysteine (SEC) and S-methyl cysteine (SMC) in garlic extracts were all increased by fermentation with lactic acid bacteria. However, alliin in the fermented garlic extracts with lactic acid bacteria strains was lower than the original garlic extract and the contents of cycloalliin in the garlic extracts did not change with fermentation (p<0.05). The electron donating ability of the fermented garlic extracts increased with dose. The electron donating ability of the fermented garlic extract with L. plantarum and P. pentosaceus was over 90% efficient at 5 mg/g. The fermented garlic extracts (with lactic acid bacteria) and garlic extract were not influenced, up to $100{\mu}g/mL$, in CYPE1-transfected HepG2 cells. The CYPE1-transfected HepG2 cell viabilities were 92.60% and 92.23% when treated with both alcohol (200 mM) and fermented garlic extract ($100{\mu}g/mL$) with lactic acid bacteria respectively, for 6 days.

Pharmacokinetic Interaction Between Diltiazem and Naringenin in Rabbits (나린제닌과 딜티아젬과의 약물동태학적 상호작용)

  • Seol, Hyo-Chan;Choi, Jun-Shik
    • Korean Journal of Clinical Pharmacy
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    • v.16 no.1
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    • pp.57-62
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    • 2006
  • The purpose of this study was to investigate the effect of naringenin, one of flavonoids, on the pharmacokinetics and bioavailability of diltiazem (15 mg/kg) after oral administration of diltiazem with or without naringenin (2.0, 10 and 20 mg/kg) in rabbits. Coadministration of naringenin increased the absorption rate constant $(K_a)$, the area under the plasma concentration-time curve (AUC) and peak concentration $(C_{max})$ of diltiazem compared to the control group, but only significantly (p<0.05) by 10mg/kg of naringenin coadministration. The absolute bioavailability (AB%) of diltiazem by coadministration ranges from 7.8% to 10.3%, increased more than control (7.2%), and relative bioavailability (RB%) of diltiazem is increased from 1.08- to 1.43-fold. Coadministration caused on significant changes in the terminal half-lives $(t_{1/2})$ and the time to reach the peak concentration $(T_{max})$ of diltiazem. On the other hand, coadministration of naringenin increased the AUC desacetyldiltiazem, significantly at the dose of 10mg/kg. But the metabolite ratio (MR) was decreased, significantly at 10mg/kg of naringenin. Based on these results, we can make a conclusion that the increased bioavailability and the significant changes of these pharmacokinetic parameters might be due to naringenin, which possess the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein efflux pump in the intestinal mucosa.

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Mechanistic Insights into the Chemopreventive Action of Phenethy1 Isothiocyanate against Ν-Nitrosobis(2-Oxopropyl) Amine-Induced Carcinogenesis

  • Lee, In-Seon
    • Preventive Nutrition and Food Science
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    • v.1 no.2
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    • pp.227-229
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    • 1996
  • The effects of phenthyl isothiocyanate(PEIFTC) on xenobiotic metabolizing enzymes and cell kinetics in the target organs for Ν-nirtosobis(2-oxopropyl) amine(BOP)-tumorigenicity were investigated in female Syrian golden hamsters in order to gain the mechanistic insigths into the chemopreventive action of PEITS against BOP-initiated lung and pancreatic carcinogenesis in hamsters. Hamsters were given BOP subcuteneo-usly(s.c.) and/or PEITC by gavage 2h prior to the BOP treatment. Eight and 24h after the PEITC administration, animals were sacrificed for analyzing P450 isoenzymes, glutathine(GSH), glutathione S-transferase(GST) and cell kinetics. The PEITC pretreatment significantly reduced the hepatic P450 isoenzume levels such as CYP2B1 and DYP1A1 which were significantly increased by the BOP treatment. However, PEITC did not affect the CYP levels in the pancreas and lung. Interestingly, the PEITC pretreatment rather lowered the heparic GST and GSH levels, regradless of BOP administration. Proliferating cell nuclear antigen(PCNA)- labeling indices were dose dependently decreased by PEITC in the pancreas acini and ducts, bronchioles, and renal tubules in which the cell replication was significantly affected by BOP. These results thus suggest that PEITC exerts the chemopreventive effects in hamsters by influencing xenobiotic matabolizing phase I enzymes in the liver and regulating cell kinetics in the target organs.

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Experimental Study of Chungganhaeju-tang (Qingganjiejiu-tang) on Oxidative Stress (청간해주탕(淸肝解酒湯)의 항산화 작용에 관한 실험적 연구)

  • Lee, Ji-Eun;Lee, Jang-Hoon
    • The Journal of Internal Korean Medicine
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    • v.32 no.2
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    • pp.188-202
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    • 2011
  • Objectives : Oxidative stress seems to play a major role in mechanisms by which ethanol causes liver injury. Previous studies have shown that treatment with Chungganhaeju-tang (Qingganjiejiu-tang, CGHJT) has protective effects on alcoholic liver disease. The aim of this study was to investigate the effects of Chungganhaeju-tang on oxidative stress. Materials and Methods : In vitro, we evaluated the inhibitory activities of CGHJT on DPPH (1,1-diphenyl-2-picryl-hydrazyl), xanthine oxidase, trypsin, and hyaluronidase, and measured cell viability, and proliferation. In the cell culture model, we measured the activities of superoxide dismutase (SOD), and catalase (CAT) after CGHJT treatment in C34 and E47 cell lines, HepG2 cells transfected with/without the cytochrome P450 2E1 (CYP2E1) gene. In vivo, we measured malondialdehyde levels in the liver tissue and alcohol concentration in the blood. Results : CGHJT showed significant free radical scavenging activity against DPPH and xanthine oxidase in the in vitro study, and increased cell viability, proliferation, and activities of superoxide dismutase, catalase in C34 and in E47 cell lines. CGHJT reduced malondialdehyde levels and blood alcohol concentration in vivo, as well. Conclusions : This study suggests that CGHJT has antioxidant effects on oxidative stress by reducing lipid peroxidation and inhibiting the ethanol induced suppression of antioxidant enzyme activities.

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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    • v.24 no.1
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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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Enhanced Bioavailability of Paclitaxel by Bamboo Concentrate Administration

  • Kang Keon Wook;Choi Jun Shik
    • Archives of Pharmacal Research
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    • v.28 no.4
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    • pp.469-475
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    • 2005
  • The purpose of this study was to investigate the effect of a cotreatment of bamboo concentrates (Jukcho solution; 0.75, 1.5, and 3.0 mL/kg) with the chemotherapeutic agent paclitaxel on the bioavailability of orally administered paclitaxel (50 mg/kg) in rats. The effect of a pretreatment of bamboo concentrates (1.5 and 3.0 mL/kg for 1.0 h or a consecutive 3 day) was also examined. The paclitaxel plasma concentrations of rats orally administered paclitaxel plus bamboo concentrates (coadministration, 3.0 mL/kg and pretreatment, 1.5 and 3.0 mL/kg) were significantly higher than those of rats treated with paclitaxel alone. Plasma concentrations of paclitaxel in groups pretreated with bamboo concentrates for 3 day were markedly higher than those of a paclitaxel control group at the measured time points. The areas under plasma concentration-time curves (AUCs) of paclitaxel in groups pretreated with bamboo concentrates were elevated and the absolute bioavailability ($AB\%$) and relative bioavailability ($RB\%$) of paclitaxel were also significantly higher than those in the control group. The peak concentration ($C_{max}$), half-life ($t_{1/2}$), and the elimination rate constant ($K_{el}$) of paclitaxel after 3 day of pretreatment with bamboo concentrates were also significantly higher than those in the control, but the time required to reach the maximum plasma concentration ($T_{max}$) of paclitaxel was unaffected by the bamooo concentrates. Western blot analyses demonstrated that the level of CYP3A4 was increased in the livers of rats treated orally with paclitaxel, but this was reversed by pretreating with bamboo concentrates. These results show that bamboo concentrates enhance the bioavailability of orally administered paclitaxel and this effect may be associated with a diminished expression of CYP3A4 in the liver.

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.