• Biomolecules & Therapeutics
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• 제3권1호
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• pp.12-20
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• 1995

Clofibrate, a peroxisome proliferator, is hepatocarcinogenic in rats in a dose-dependent manner. A total of 70 male and female F344 rats, 5-week-old, were divided into three groups. Rats were fed clofibrate at 0, 0.25, or 0.5% in diet for 30 days. All rats were anesthetized with $CO_2$, blood samples were taken by cardiac puncture for hematology and clinical chemistry, and the rats were killed by exsanguination. Livers, kidenys, pancreas, adrenal glands, spleen, heart, lungs, thyroid gland, reproductive organs, and digestive organs were removed, weighed, later processed, and embedded with paraplast for histological examination. The relative liver and kidney weights with respect to final body weight in the clofibrate-treated group were significantly increased compared with those of control group at all dose levels (p<0.01). It has been suggested that clofibrate may influence on hepatotoxicity by increases in peroxisomal proliferation.

• 한국응용과학기술학회지
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• 제24권2호
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• pp.117-123
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• 2007

• Biomolecules & Therapeutics
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• 제3권2호
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• pp.132-135
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• 1995

Several clofibrate congeners (bezafibrate, gemfibrozil and fenofibrate) were investigated the relationship between effects on the aggregation induced by aggregating agents (thrombin, arachidonic acid, ADP and collagen) and arachidonic acid metabolism in rabbit homogenized platelet. In platelet aggregation study, all drugs produced no significant inhibition (data not shown) in arachidonic acid and thrombin. Also platelet aggregation by ADP was not changed in bezafibrate and Inhibited dose dependently in fenofibrate and gemfibrozil. Platelet aggregation by collagen was inhibited dose dependently and significantly (from p<0.5 to p<0.001) by gemfibrozil and fenofibrate at concentrations between 20 and 400 $\mu$M. In arachidonic acid metabolism study, synthesis of thromboxane $B_2$ was not changed in rabbit platelet membranes and that of prostaglandin $E_2$ and $F_{2{\alpha}}$ was slightly increased by all drugs. It was concluded that clofibrate congeners inhibited ADP and collagen induced rabbit platelet aggregation and inhibition of collagen induced aggregation was probably mediated through some mechanism (pathway) other than arachidonic acid metabolism, judging from arachidonic acid metabolites (thromboxane $B_2$, prostaglandin $E_2$and $F_{ 2{\alpha}}$) synthesis in rabbit homogenized Platelet.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2004년도 KSOT/KEMS Fall Annual Meeting
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• pp.35-36
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• 2004

• 한국독성학회:학술대회논문집
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• 한국독성학회 2004년도 KSOT/KEMS fall annual meeting
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• pp.35-36
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• 2004

• KSBB Journal
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• 제16권3호
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• pp.253-258
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• 2001

항고지단백혈증제제를 이용한 경펴투과제제흘 제조하고자 기 재로서 xathan gum을 사용하여 약물의 함량 및 투과 촉전제에 따라서 경피투과체제를 제조하고 경피투과 항고지단백혈증제의 가능성 등을 연구하였다. 기재로 사용한 xanthan gum의 체 타전위를륜 측정하여 응결, 침전이 나타나는 등천점으로부터 제타전위 값의 차이가 나타나 있으므로 피부와 접촉시 연고제제외 석출 가능성이 없다는 것을 확인할 수 있었다. 각각의 지용성과 수용성 항고지단백혈증제제를 함유한 정피투과제제를 사용하여 진행된 투과 실험에서는 자용성인 clofibrat$\xi$의 투파속도가 현저하게 빠르게 나타났는데 이는 지용성인 피부 각질과의 친화 즉 lipophilicity를 증가시킴으로써 지용성인 clofibrate의 경피투과를 촉진시키는 것이라 생각된다. 지용성 경피투과제제에 투과촉진제를 첨가했을 경우, 그렇지 않은 경우에 비해 lag time파 투과속도가 빠르게 나타냈다. 특히 PEG 600을 사용했윤 경우가 가장 빠른 투과속도흘 나타냈고 글리세린, 올레산의 순오로 투과속도의 증가를 나타냈다. PEG 600븐 다른 투과촉진제보다 지용성 약물인 clofibrate에 대해 피부내의 지방과 단백겔의 유동성(fluidity) 과 피부 각질의 lipophilicity를 증가시컴으로서 각질로의 약물분배를 촉진한다고 생각된다.

• 한국환경성돌연변이발암원학회지
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• 제19권2호
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• pp.89-94
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• 1999

Cell proliferation and c-Jun expression pattern in liver exposed by nongenotoxic carcinogens phenobarbital (PB) and clofibrate, and genotoxic carcinogen 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) were investigated to see whether differential effects of genotoxic and non-genotoxic carcinogens on the development of neoplastic foci may be related to differential effect on cell proliferation. Male F344 rats were initially given a single intraperitioneal injection of diethylnitrosamine (200 mg/kg body weight), and 2 weeks later, animals were fed diets containing 0.03% IQ or 0.5% CE or 0.05% PB or basal diet as a control for 6 weeks. All rats were subjected to the two-thirds partial hepatectomy (PH) at week 3. Sequential sacrifice of rats was performed until 8 weeks. Cell proliferation was examined by immunohistochemical staining of bromodeoxyuridine and c-Jun expression was determined by northern blotting. The increase of cell proliferation rate after PH was significant in the rats fed 0.05% IQ and continued until 8 weeks, while the increase was not significant in the rats fed phenobarbital and clofibrate compared to that in the rats fed control diet. mRNA level of c-Jun in the liver treated with IQ was about 7 fold higher than that of control and peak at 5 hours after rH. In the liver treated with CE, mRNA level of c-Jun was 3-4 fold higher than that of control and the highest level of mRNA of c-Jun was seen at 24 hours after PH. These results show that differential effects of genotoxic and non-genotoxic carcinogens on the development of neoplastic foci may be related to differential effect on cell proliferation pattern.

• Nutrition Research and Practice
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• 제13권4호
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• pp.286-294
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• 2019

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of ${\alpha}$-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by $PPAR{\alpha}$. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among $PPAR{\alpha}$ homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate ($PPAR{\alpha}$ agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: $PPAR{\alpha}$ ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, $PPAR{\alpha}$ activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by $PPAR{\alpha}$. Either $PPAR{\alpha}$ deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

• Archives of Pharmacal Research
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• 제21권1호
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• pp.35-40
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• 1998

Human cytochrome P450 4F2 shows high regioselectivity in hydroxylation of stearic acid and leukotriene $ B_4.$ As a first step of its regulation study, human cytochrome P450 4F2 genomic DNA was isolated from liver of a person who was administered clofibrate for 10 years. From Southern hybridization, restriction enzyme digestion and sequencing experiments, isolated genomic DNA fragment was found to contain around 32 Kb DNA and more than 20 Kb of $5^I$ end regulatory region. Sequences of the structural gene region revealed exon 1 and exon 2. Further regulation studies would elucidate the feedback mechanisms of the oxidative degradation of fatty acids, inflammatory response and the clearance of leukotriene B4 in the liver. Furthermore, regulation study of this gene could explain the species difference in responses to peroxisome proliferator and help in the safety evaluation of peroxisome proliferating chemicals to human being.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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• pp.159-159
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• 2001

The phthalates have been shown to produce hepatic peroxisome proliferation and certain peroxisome proliferators (PPs) are also known to increase the incidence of liver tumors in rodents. In this study we investigated the correlation between oxidative injury, changes in peroxisomal and microsomal enzymes and tumor formation in PP-treated rats.(omitted)