1,2-Dimethylhydrazine에 의해 유발된 Colonic Aberrant Crypt Foci에 대한 KTG075의 암예방효과

김영숙(Young-Sook Kim),백순옥(Soon-Ok Baik),김현경(Hyun-Kyung Kim),이유희(You-Hui Lee),한명규(Myung Kyu Han),김태명(Tae Myung Kim),김대중(Dae Joong Kim) 한국실험동물학회 2005 Laboratory Animal Research Vol.21 No.1

The present study was designed to investigate the chemopreventive effects of KTG075, which is a mixture of nine herbs with anti-constipation activity in Ioperamide-treated rats, on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in rat colonic mucosa. KTG075 was administered in the drinking water (3.2 ㎎/㎖) during the initiation (for 12 weeks) or postinitiation phase (for 9 weeks) of DMH-induced carcinogenesis. KTG075 coupled with DMH for 12 weeks significantly decreased total number of aberrant crypts (pre-neoplastic lesions) and the number of ACF to 35% and 30%, respectively. The number of ACF with more than four aberrant crypts (crypt multiplicity) significantly reduced in the colon of rats treated with KTG075 for 12 weeks. In the group receiving KTG075 during post-initiation stage for 9 weeks, only the number of ACF with more than four aberrant crypts significantly decreased. KTG075, given alone for 12 weeks, did not induced the development of ACF. These findings indicate that KTG075 may have possess chemopreventive effects on chemically induced rat colon carcinogenesis.

Estrogen receptor independent neurotoxic mechanism ofbisphenol A, an environmental estrogen

Yoot Mo Lee,홍진태,Min Jae Seong,Jae Woong Lee,Yong Kyung Lee,김태명,남상윤,김대중,윤영원,Tae Seong Kim,Soon Young Han 대한수의학회 2007 Journal of Veterinary Science Vol.8 No.1

Bisphenol A (BPA), a ubiquitous environmental contaminant, has been shown to cause developmental toxicity and carcinogenic effects. BPA may have physiological activity through estrogen receptor (ER) -α and -β, which are expressed in the central nervous system. We previously found that exposure of BPA to immature mice resulted in behavioral alternation, suggesting that overexposure of BPA could be neurotoxic. In this study, we further investigated the molecular neurotoxic mechanisms of BPA. BPA increased vulnerability (decrease of cell viability and differentiation, and increase of apoptotic cell death) of undifferentiated PC12 cells and cortical neuronal cells isolated from gestation 18 day rat embryos in a concentration-dependent manner (more than 50 μM). The ER antagonists, ICI 182,780, and tamoxifen, did not block these effects. The cell vulnerability against BPA was not significantly different in the PC12 cells overexpressing ER-α and ER-β compared with PC12 cells expressing vector alone. In addition, there was no difference observed between BPA and 17-β estradiol, a well-known agonist of ER receptor in the induction of neurotoxic responses. Further study of the mechanism showed that BPA significantly activated extracellular signal-regulated kinase (ERK) but inhibited anti-apoptotic nuclear factor kappa B (NF-κB) activation. In addition, ERK-specific inhibitor, PD 98,059, reversed BPA-induced cell death and restored NF-κB activity. This study demonstrated that exposure to BPA can cause neuronal cell death which may eventually be related with behavioral alternation in vivo. However, this neurotoxic effect may not be directly mediated through an ER receptor, as an ERK/NF-κB pathway may be more closely involved in BPA-induced neuronal toxicity.

가미귀비탕의 4주 반복투여독성 평가

황석연(Seock-Yeon Hwang),권운(Woon Kwon),채희열(Hee-Youl Chai),조영민(Young-Min Cho),류재면(Jae Myun Ryu),김동규(Dong Kyu Kim),신지순(Ji Soon Sin),김태명(Tae Kyung Kim),조정희(Jung-Hee Cho),신선희(Sunhee Shin),박정휘(Jung-Hui Park) 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.3

Four-week repeated-dose toxicity of Kamiguibitang was investigated in rats. Male Sprague-Dawley rats were orally administered with Kamiguibitang at doses of 200, 800, 1,600 or 3,200 ㎎/㎏/day or its vehicle for 28 days. There were no significant differences in the body weight gain between vehicle control and Kamiguibitang-treated groups. Significant changes in daily feed intake and water consumption were not observed throughout the experimental period. There were trends of increase in platelets and white blood cells, in parallel with increases in serum globulin level and spleen weight, suggestive of inflammatory response and/or immune enhancement. Serum parameters of hepatic and renal injuries, such as aspartate transaminase, alanine transaminase, alkaline phosphatase, cholesterol, triglyceride, creatinine, phosphorus, calcium, sodium and potassium, also increased at low doses (200-800 ㎎/㎏) of Kamiguibitang, although the levels were suppressed at high doses (1,600-3,200 ㎎/㎏). However, no gross and histopathological lesions were seen at all doses. Based on the results, no observed adverse effect level (NOAEL) of Kamiguibitang was found to be lower than 200 ㎎/㎏, which is comparable with clinical dose (100 ㎎/㎏) in human. In spite of the relatively-low NOAEL, it is suggested that repeated treatment with Kamiguibitang may not exert considerable adverse effects, as inferred from that major hematological and blood biochemical changes were results of pharmacological effectiveness on immunomodulation, and that no histopathological lesions were exerted up to 32 folds of clinical dose (3,200 ㎎/㎏),

관상 동맥 질환에서 아포 E 지단백 유전자 다형성과 혈청 지질치와의 관계

곽선영,김성구,정호석,이유경,이광희,김철현,최태명,현민수,권영주 순천향의학연구소;Soonchunhyang Medical Research Institute 2000 Journal of Soonchunhyang Medical Science Vol.6 No.1

Background and aims: The Apolipoprotein E is a ligand of both the protein component LDL receptor as well as the apo E LDL-Receptor related protein (LRP). It modulates the receptor binding of lipoproteins, with the apolipoprotein E found on cell surfaces as its component, thus serving an important role in the lipid metabolism by carrying out the intracellular transport of cholesterol in lipoproteins. The gene for apolipoprotein E is the product of three common genotypes as well as many more rare alleles. The common genotypes are ε2, ε3, and ε4, and are expressed in the three phenotype isoforms of E2, E3, and E4. In the event that E4 is the main component, a rise in the cholesterol level, as the result of down-regulation of the LDL receptor, is observed. Therefore, those samples with E4 genotypes are known to be in much higher risk of coronary artery disease than those with ε3/ε3, while those with ε2 are in low risk (with the exception of hypertiglyceremai Ⅲ). The aim of this study is to analyze in patients with ischemic heart disease the role of aplipoprotein E alleles in order to seek its correlation with coronary artery disease, as well as to seek whether the polymorphism of apo E produces any differences in the severity of coronary artery disease according to plasma lipid levels. Methods: The subjects for study were 273 patients admitted to the Internal Cardiology Division of the Soonchunhyang University Hospital form December 1998 to February 1999. The subjects were divided into the two groups of which one was ischemic heart disease (IHD) experiment group totaling 105 (avg.60.1 years of age, male/female ratio = 69/36) and the control group totaling 168 (avg. 59.7 years of age, male/female = 73:95). The coronary angiogram was given to 127 subjects, and of this total, 94 have developed significant stenosis in the coronary artery. The stages of the analyzing of the apo E phenotype was first, the separation of DNA from the blood samples, subjecting it to the PCR from with 228 base pairs of expanded products were obtained. The band was determined by means of the reverse hybridization principle on the nitrocellulose strip. Results: From the 105 patients the distributions of apo E phenotypes were as follows: ε3/2(5.7%), ε4/2(1.9%), ε3/3(70%), ε4/3(20%), ε4/4(1.9%). The relative frequencies of each allele are as follow: ε2 (0.038), ε3 (0.833), ε4 (0.128). The results show as follows: ⅰ) The IHD experiment group to have a higher occurrence of ε4/3 phenotypes as well as ε4 alleles than the control group. ⅱ) Both the control group and IHD group showed the largest distribution of ε3/3 for phenotypes, and ε4 for alleles. ⅲ) The IHD group showed less ε2/3 phenotypes as well as significantly less allele frequency of ε3 in comparison to the control group. ⅳ) the IHD group showed a much lower level of HDL in comparison to the control group, while the LDL was significantly higher; samples including the apo ε2 showed a significantly higher level of HDL than those without. Among the control group, samples including apo ε2 showed a significantly higher level of TG (triglyceride) than samples without. No significant difference was found between the experiment apo ε4 sample and the control plasma lipid sample. ⅴ) No significant correlation was found between an apo E polynorphism and the number of involved arteries of a coronary angiogram. Conclusion: Between the experiment IHD group and control group were found differences in the frequency of alleles. The polymorphism of apo E alleles may contribute as a risk factor to the development of heart disease by involving itself in the metabolism and modulation of plasma lipids.