• 대한임상약리학회:학술대회논문집
• /
• 대한임상약리학회 2006년도 제15차 추계학술대회
• /
• pp.88-88
• /
• 2006

• Toxicological Research
• /
• 제18권4호
• /
• pp.331-339
• /
• 2002

Phenoxy compounds, 2,4-Dichlorophenol acetoxy acid (2,4-D) and 2,4-dichlorophenol (DCP), are widely used as a hormonal herbicide and intermediate for pesticide manufacturing, respectively. In order to assess the potential of these compounds as endocrine disruptors, we studied the androgenicity of them wing in vivo and in vitro androgenicity assay system. Administration of 2,4-D (50 mg/kg/day, p.o.) or DCP (100 mg/kg/day, p.o.) to rats caused an increase in the tissue weight of ventral prostate, Cowpers gland and glands penis. These increase of androgen-dependent tissues were additively potentiated when rats were simultaneously treated with low dose of testosterone (1 g/kg, s.c.). 2,4-D increased about 350% of the luciferase activity in the PC cells transiently cotransfected phAR and pMMTV-Luc at concentration of $10^{-9}$ M. In 2,4-D or DCP-treated castrated rats, testosterone 6$\beta$-hydroxylase activity was not significantly modulated even when rats were co-treated with testosterone. In vitro incubation of 2,4-D and DCP with microsomes at 50 $\mu$M inhibited testosterone 6$\beta$-hydroxylase activity about 27% and 66% in rat liver microsomes, about 44% and 54% in human liver microsomes and about 50% and 45% in recombinant CYP3A4 system, respectively. The amounts of total testosterone metabolites were reduced about 33% and 75% in rat liver microsomes, 69% and 73% in human liver microsomes and 54% and 64% in recombinant CYP3A4 by 2,4-D or DCP, respectively. Therefore, the additive androgenic effect of 2,4-D or DCP by the co-administration of the low dose of testosterone may be due to the increased plasma level of testosterone by inhibiting the cytochrome P450-mediated metabolism of testosterone. These results collectively suggested that 2,4-D and DCP may act as androgenic endocrine disrupter by binding to the androgen receptor as well as by inhibiting the metabolism of testosterone.

• 대한임상약리학회:학술대회논문집
• /
• 대한임상약리학회 2001년도 제10차 추계학술대회
• /
• pp.41-41
• /
• 2001

• 생물정신의학
• /
• 제8권2호
• /
• pp.208-219
• /
• 2001

The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.

• 생명과학회지
• /
• 제28권2호
• /
• pp.176-186
• /
• 2018

김(Porphyra yezoensis, Laver)의 MeOH 추출에 의한 유기용매 별 분획물에서 폴리페놀 함량과 항산화 활성 및 간암세포주 HepG2의 세포증식 억제효과를 확인하였다. $CHCl_3$ 분획물의 폴리페놀 함량은 $10.34{\mu}g/mg$으로 물 분획물의 $13.08{\mu}g/mg$ 보다는 다소 적게 나타났으나, DPPH 자유라디칼 소거에 의한 전자공여능(EDA)에서 나타난 $ED_{50}$은 $16.96{\mu}g/ml$로 가장 높게 나타났다. $CHCl_3$과 EtOAc 분획물은 농도의존적으로 HepG2 세포의 증식을 억제하였으며, 특히 $900{\mu}g/ml$의 $CHCl_3$ 분획물을 24시간 동안 처리하여 90%의 세포증식이 억제되었다. 한편 $CHCl_3$ 분획물이 처리된 HepG2 세포의 유전자 발현 양상을 microarray로 확인하였다. P. yezoensis의 효능과 연관지은 gene ontology 분석으로 비타민 D 합성 과정, 항균작용에 대한 반응 및 영양물질에 대한 반응에 관련된 유의 유전자들을 탐색하였다. 유의 유전자로 IL6R와 CYP1A1를 선정하였고, 이들 유전자의 상위 조절자는 ARNT 유전자가 선정되었다. 또한 50 및 $100{\mu}g/ml$의 $CHCl_3$ 분획물이 처리된 HepG2 세포에서 IL6R와 CYP1A1 단백질의 발현과 상위 조절자인 ARNT의 활성을 Western blotting으로 확인하였다.

• 한국식품영양과학회지
• /
• 제42권3호
• /
• pp.342-347
• /
• 2013

마늘에 적용가능 한 유산균을 찾기 위해 마늘 이외의 배지 성분 없이 각각의 유산균을 배양하고 유산균발효마늘 추출물을 제조하여 각각의 추출물의 유기황화합물을 분석하고 항산화효과 및 알코올 유발 세포독성에 미치는 영향을 알아보았다. 마늘멸균액을 배지로 유산균을 48시간 배양하였을 때 L. plantarum이 가장 잘 자랐으며 유산균발효마늘 추출물 중 항산화활성 등의 효능이 있는 것으로 알려진 SAC 함량은 L. plantarum의 발효물과 P. pentosaceus의 발효물이 각각 3.619 mg/g과 3.234 mg/g으로 가장 많은 것으로 나타났다(p<0.05). 그리고 SAC, SEC, SMC의 경우 유산균발효 마늘 추출물들이 마늘 추출물에 비해 높았으나 alliin의 경우 유산균발효마늘 추출물들이 마늘 추출물에 비하여 낮은 것으로 나타났다(p<0.05). 또한 cycloalliin의 경우 마늘 추출물과 유산균발효마늘 추출물들 간의 함량 차이는 없었다(p<0.05). 모든 유산균발효마늘 추출물이 농도 의존적으로 항산화활성이 높은 것으로 나타났으며, L. plantarum의 발효물과 P. pentosaceus의 발효물이 5.0 mg/g의 농도에서 90% 이상의 높은 전자공여능을 효과를 나타냈다. 유산균발효마늘 추출물들이 $100{\mu}g/mL$의 농도까지 CYP2E1 transfected HepG2 세포주에 영향을 주지 않았으며, 각각의 유산균발효 마늘 추출물을 알코올에 의해 손상된 CYP2E1 transfected HepG2 세포의 보호효과를 확인한 결과 에탄올과 시료를 6일간 처리한 경우에 FGPP와 FGLP가 각각 92.60%와 92.23%로 유의적으로 가장 높은 세포생존율을 보였다(p<0.05).

• 대한임상약리학회:학술대회논문집
• /
• 대한임상약리학회 2001년도 제10차 추계학술대회
• /
• pp.40-40
• /
• 2001

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

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권6호
• /
• pp.2711-2715
• /
• 2012

Background: Bisphenol A (BPA), an endocrine disrupting chemical, has been suspected to pose carcinogenic risks. However, likely mechanisms are obscure and there are difficulties to estimating its real significance for cancer development. Methods: We therefore studied BPA-induced proteomic alterations in immune organs of ICR mice offspring that were prenatally exposed to BPA (15 and 300 mg/L of drinking water). We performed 2D-gel analyses of samples, considering differences in spleen, exposure levels, sex, and ages. Results: From proteomic analyses, we found various proteins were up- or down-regulated by BPA. Among them, SET, a putative oncogene and inhibitor of phosphatase 2A, was significantly down-regulated in a BPA dose-dependent manner. We also confirmed down-regulation of SET in western blot and real time PCR analyses. From gene network analysis, SET is predicted to communicate with other genes including CYP17, which is involved in biosynthesis and metabolism of sex-hormones. Conclusions: This study provided evidence that SET can be applied as a new biomarker for prenatal BPA exposure and suggests a potential new mechanism of action in that BPA may disrupt CYP17 via SET.

• 대한임상약리학회:학술대회논문집
• /
• 대한임상약리학회 2003년도 제12차 추계학술대회
• /
• pp.13-13
• /
• 2003