• Archives of Pharmacal Research
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• 제24권1호
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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 $50^{\circ}C$.

• 한국식품영양과학회:학술대회논문집
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• 한국식품영양과학회 2004년도 Annual Meeting and International Symposium
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• pp.65-70
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• 2004

Modulation of biotransformation enzymes is one mechanism by which a diet high in fruits and vegetable may influence cancer risk. Inhibition of cytochrome P450s (CYP) and concomitant induction of conjugating enzymes are hypothesized to reduce the impact of carcinogens in humans. Thus, exposure to types and amounts of phytochemicals may influence disease risk. Like other xenobiotics, many classes of phytochemicals are rapodly conjugated with glutathione, glucuronide, and sulfate moieties and excreted in urine and bile. In humans, circulating phytochemical levels very widely among individuals even in response to controlled dietary interventions. Polymorphisms in biotransformation enzymes, such as the glutathione S-transferases (GST), UDP-glucuronosyltransferases (UGT), and sulfotransferases (SULT), may ocntribute to the variability in phytochemical clearance and efficacy; polymorphic enzymes with lower enzyme activity prolong the half-lives of phytochmicals in vivo. Isothiocyanates (ITC) in cruciferous vegetables are catalyzed by the four major human GSTs: however reaction velocities of the enzymes differ greatly. In some observational studies of cancer, polymorphisms in the GSTMI and GSTTI genes that result in complete lack of GSTM1-1 protein, respectively, confer greater protection from cruciferous vegetable in individuals with these genotypes. Similarly, we have shown in a controlled dietary trial that levels of GST-alpha-induced by ITC-are higher in GSTMI-null individuals exposed to cruciferous vegetablse. The selectivity of glucuronosyl conjugation of flavonoids is dependent both on flavonoid structure as well as on the UGI isozyme involved in its conjuagtion. The effects of UGI polymorphisms on flavonoid clearnace have not been examind; but polymorphisms affect glucuronidation of several drugs. Given the strong interest in the chemopreventive effects of flavonoids, systematic evaluation of these polymorphic UGTs and flavonoid pharmacokinetics are warranted. Overall, these studies suggest that for phytochemicals that are metabolized by, and affect activity of, biotransformation enzymes, interactions between genetic polymorphisms in the enzymes and intake of the compounds should be considered in studies of cancer risk. Genetic polymorphisms in biotransformation enzymes may account in prat for individual variation in metabolism of a wide range of phytochemicals and their ultimate impact on health.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3761-3768
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• 2013

Background: The Saudi population has experienced a sharp increase in colorectal and gastric cancer incidences within the last few years. The relationship between gene polymorphisms of xenobiotic metabolizing enzymes and colorectal cancer (CRC) incidence has not previously investigated among the Saudi population. The aim of the present study was to investigate contributions of CYP1A1, CYP2E1, and GSTM1 gene polymorphisms. Materials and Methods: Blood samples were collected from CRC patients and healthy controls and genotypes were determined by polymerase chain reaction restriction fragment length polymorphism and sequencing. Results and Conclusions: $CYP2E1^*6$ was not significantly associated with CRC development (odd ratio=1.29; confidence interval 0.68-2.45). A remarkable and statistically significant association was observed among patients with $CYP1Awt/^*2A$ (odd ratio=3.65; 95% confidence interval 1.39-9.57). The $GSTM1^*0/^*0$ genotype was found in 2% of CRC patients under investigation. The levels of CYP1A1, CYP2E1 and GSTM1 mRNA gene expression were found to be 4, 4.2 and 4.8 fold, respectively, by quantitative real time PCR. The results of the present case-control study show that the studied Saudi population resembles Caucasians with respect to the considered polymorphisms. Investigation of genetic risk factors and susceptibility gene polymorphisms in our Saudi population should be helpful for better understanding of CRC etiology.

• Asian-Australasian Journal of Animal Sciences
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• 제25권6호
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• pp.794-799
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• 2012

The cytochrome P450c17-I (CYP17-I) is one of the enzymes critical to gonadal development and the synthesis of androgens. Two single nucleotide polymorphisms (SNPs) were detected within the coding region of the CYP17-I gene in a population of 75 male Japanese flounder (Paralichthys olivaceus). They were SNP1 (c.C445T) located in exon2 and SNP2 (c.T980C (p.Phe307Leu)) located in exon5. Four physiological indices, which were serum testosterone (T), serum $17{\beta}$-estradiol ($E_2$), Hepatosomatic index (HSI), and Gonadosomatic index (GSI), were studied to examine the effect of the two SNPs on the reproductive endocrines of Japanese flounder. Multiple comparisons revealed that CT genotype of SNP1 had a much lower T level than CC genotype (p<0.05) and the GSI of individuals with CC genotype of SNP2 was higher than those with TT genotype (p<0.05). Four diplotypes were constructed based on the two SNPs and the diplotype D3 had a significantly lower T level and GSI. In conclusion, the two SNPs were significantly associated with reproductive traits of Japanese flounder.

• Korean Journal of Acupuncture
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• 제19권2호
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• pp.57-61
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• 2002

천궁약침액을 7일간 중완혈, 간수혈 및 임의혈에 투여한 후 마우스의 간에서 유도되는 phase I enzyme 억제 효과를 살펴본 결과 천궁 약침액은 CYP 1A1를 저해하였고, 생체의 CYP 2E1의 활성도 억제하였으므로 천궁 약침액은 암예방 효과가 있을 것으로 사료된다.

• 생약학회지
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• 제33권1호통권128호
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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 $50\;{\mu}g/ml$.

• Nutrition Research and Practice
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• 제7권4호
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• pp.287-293
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• 2013

This study determined the effects of fucoxanthin on gene expressions related to lipid metabolism in rats with a high-fat diet. Rats were fed with normal fat diet (NF, 7% fat) group, high fat diet group (HF, 20% fat), and high fat with 0.2% fucoxanthin diet group (HF+Fxn) for 4 weeks. Body weight changes and lipid profiles in plasma, liver, and feces were determined. The mRNA expressions of transcriptional factors such as sterol regulatory element binding protein (SREBP)-1c, Carnitine palmitoyltransferase-1 (CPT1), Cholesterol $7{\alpha}$-hydroxylase1 (CYP7A1) as well as mRNA expression of several lipogenic enzymes were determined. Fucoxanthin supplements significantly increased plasma high density lipoprotein (HDL) concentration (P < 0.05). The hepatic total lipids, total cholesterols, and triglycerides were significantly decreased while the fecal excretions of total lipids, cholesterol, and triglycerides were significantly increased in HF+Fxn group (P < 0.05). The mRNA expression of hepatic Acetyl-CoA carboxylase (ACC), Fatty acid synthase (FAS), and Glucose-6-phosphate dehydrogenase (G6PDH) as well as SREBP-1C were significantly lower in HF+Fxn group compared to the HF group (P < 0.05). The hepatic mRNA expression of Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and Acyl-CoA cholesterol acyltransferase (ACAT) were significantly low while lecithin-cholesterol acyltransferase (LCAT) was significantly high in the HF+Fxn group (P < 0.05). There was significant increase in mRNA expression of CPT1 and CYP7A1 in the HF+Fxn group, compared to the HF group (P < 0.05). In conclusion, consumption of fucoxanthin is thought to be effective in improving lipid and cholesterol metabolism in rats with a high fat diet.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.288-295
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• 2017

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with $20{\mu}M$ $bosentan+200{\mu}M$ rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

• Toxicological Research
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• 제31권4호
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• pp.355-361
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• 2015

The aim of this study was to investigate whether genetic polymorphisms of CYP2E1, GSTM1, and GSTT1 and lifestyle habits (smoking, drinking, and exercise) modulate the levels of urinary styrene metabolites such as mandelic acid (MA) and phenylglyoxylic acid (PGA) after occupational exposure to styrene. We recruited 79 male workers who had received chronic exposure in styrene fiberglass-reinforced plastic manufacturing factories. We found that serum albumin was significantly correlated with blood styrene/ambient styrene (BS/AS), urinary styrene (US)/AS, and US/BS ratios as well as urinary metabolites, that total protein correlated with US/MA and US/PGA ratios, and that low density lipoprotein (LDL)-cholesterol significantly correlated with US/BS, US/MA, and US/PGA ratios. Multiple logistic regression analyses using styrene-metabolizing enzyme genotypes and lifestyle habits as dependent variables and blood and urine styrene concentrations and urine styrene metabolite levels as independent variables revealed that $CYP2E1^*5$ was associated with the MA/US ratio and GSTM1 with US/BS, that a smoking habit was associated with US/AS and MA/US ratios and MA and PGA levels, and that regular exercise was correlated with PGA/US. In conclusion, the results suggested that genetic polymorphisms of styrene-metabolizing enzymes, lifestyle behaviors, and albumin and LDL-cholesterol serving as homeostasis factors together are involved in styrene metabolism.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.1049-1052
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• 2013

Background: Studies have shown that alterations of steroid hormone metabolism, particularly involving testosterone, affect the risk of prostate cancer. Therefore, genetic variation in genes of enzymes which are involved could be of importance. The gene most interest is CYP17, whose enzyme product has an essential role in testosterone hormone synthesis. Some studies have indicated that the A2 allele polymorphism of CYP17 associated with increased risk of prostate cancer that could be affected by ethnicity. Therefore, the aim of this study was determination of presence or absence of the A2 allele in patients with prostate cancer. Materials and Methods: We studied the association of A2 allele and prostate cancer among 74 patients with prostate cancer and 128 healthy men which were referred to hospitals of SBMU. Results: This study revealed a significant association between prostate cancer risk and the A2 allele in an Iranian population so that A1A2 and A2A2 genotypes were more common in cases than controls with P-values of 0.029 and 0.010, respectively. Conclusions: Results of our study support a possible role of the A2 allele in sporadic prostate cancer development in Iran, in line with findings elsewhere.