• 대한생식의학회:학술대회논문집
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• 2002.11a
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• pp.74.2-75
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• 2002

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.6
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• pp.767-774
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• 2011

Defatted green tea seed was extracted with 100% ethanol for 4 hr and then fractionated with petroleum ether, ethyl acetate and butanol. The ethanol and butanol extracts showed greater increases in antiproliferation potential against liver cancer cells than petroleum ether, ethyl acetate, $H_2O$, and hot water extracts did. Thus, this study was carried out to investigate the anti-proliferative actions of defatted green tea seed ethanol extract (DGTSE) in HepG2 cancer cells. The DGTSE contained catechins including EGC ($1039.1{\pm}15.2\;g/g$), tannic acid ($683.5{\pm}17.61\;{\mu}g/g$), EC ($62.4{\pm}5.00\;{\mu}g/g$), ECG ($24.4{\pm}7.81\;{\mu}g/g$), EGCG ($20.9{\pm}0.96\;{\mu}g/g$) and gallic acid ($2.4{\pm}0.68\;{\mu}g/g$), but caffeic acid was not detected when analyzed by HPLC. The anti-proliferation effect of DGTSE toward HepG2 cells was 83.13% when treated at $10\;{\mu}g$/mL, of DGTSE, offering an $IC_{50}$ of $6.58\;{\mu}g$/mL. DGTSE decreased CYP1A1 and CYP1A2 protein expressions in a dose-dependent manner. Quinone reductase and antioxidant response element (ARE)-luciferase activities were increased about 2.6 and 1.94-fold at a concentration of $20\;{\mu}g$/mL compared to a control group, respectively. Enhancement of phase II enzyme activity by DGTSE was shown to be mediated via interaction with ARE sequences in genes encoding the phase enzymes. DGTSE significantly (p<0.05) suppressed prostaglandin $E_2$ level, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) protein expressions, and NF${\kappa}$B translocation, but did not affected nitric oxide production. From the above results, it is concluded that DGTSE may ameliorate tumor and inflammatory reactions through the elevation of phase II enzyme activities and suppression of NF${\kappa}$B translocation and TNF-${\alpha}$ protein expressions, which support the cancer cell anti-proliferative effects of DGTSE in HepG2 cells.

• 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.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.10.1-10.8
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• 2016

Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and $17{\beta}$-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases ($3{\beta}$-HSD2 and $17{\beta}$-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and $100{\mu}g/mL$) showed a significant decrease in $17{\beta}$-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and $17{\beta}$-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and $17{\beta}$-HSD1, and lead to a decrease in $17{\beta}$-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7195-7200
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• 2014

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

• Journal of Microbiology and Biotechnology
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• v.26 no.3
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• pp.498-502
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• 2016

3'-Hydroxygenistein can be obtained from the biotransformation of genistein by the engineered Pichia pastoris X-33 strain, which harbors a fusion gene composed of CYP57B3 from Aspergillus oryzae and a cytochrome P450 oxidoreductase gene (sCPR) from Saccharomyces cerevisiae. P. pastoris X-33 mutants with higher 3'-hydroxygenistein production were selected using a periodic hydrogen peroxide-shocking strategy. One mutant (P2-D14-5) produced 23.0 mg/l of 3'-hydroxygenistein, representing 1.87-fold more than that produced by the recombinant X-33. When using a 5 L fermenter, the P2-D14-5 mutant produced 20.3 mg/l of 3'-hydroxygenistein, indicating a high potential for industrial-scale 3'-hydroxygenistein production.

• 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.

• Environmental Analysis Health and Toxicology
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• v.24 no.1
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• pp.1-8
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• 2009

In this study, we obtained the fertilized eggs from goldfish(Carassius auratus) and observed normal developmental stage(from fertilized eggs to larvae) in non-exposed groups. Goldfish embryos at 3 h postfertilization(hpf) were statically exposed for 1 h to either dimethylsufoxide(DMSO, 0.1%, v/v) or TCDD($0.5{\mu}g/L$). Toxicity and morphological changes were characterized from 3 to 120 h postfertilization(hpf). Egg mortality($0{\sim}48$ hpf) and hatching ratio($72{\sim}83$ hpf) in TCDD-exposed group were significantly different from control groups. However, pericardial edema was first observed at 72 hpf, followed by the onset of yolk sac edema and mortality. In addition, goldfish embryos-larvae exposed to TCDD significantly increased TCDD-related gene such as CYP1A($24{\sim}72$ hpf) and AhR2(72 hpf). This is the first study about in-depth characterization of TCDD-induced developmental toxicity in goldfish(Carassius auratus).

• Korean Journal of Clinical Pharmacy
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• v.20 no.3
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• pp.200-204
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• 2010

The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of nimodipine in rats. Pharmacokinetic parameters of nimodipine were determined in rats after oral administration of nimodipine (16 mg/kg) with or without ticlopidine (3 or 10 mg/kg). Ticlopidine inhibited cytochrome P450 (CYP)3A4 activity. Ticlopidine significantly (p<0.05, 10 mg/kg) increased the area under the plasma concentration-time curve (AUC) of nimodipine and ticlopidine significantly (p<0.05, 10 mg/kg) prolonged the terminal half-life ($t_{1/2}$) of nimodipine. Ticlopidine significantly (p<0.05, 10 mg/kg) decreased the total body clearance ($CL_t$). The absolute bioavailability (AB%) and relative bioavailability (RB%) of nimodipine by presence of ticlopidine were increased by 14% and by 42%, respectively, compared to the control. Based on these results, the increased bioavailability of nimodipine might be due to inhibition of the metabolizing enzyme cytochrome P450 (CYP)3A4 in the liver or intestinal mucosa and/or reducing total body clearance by ticlopidine.