• Mass Spectrometry Letters
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• 제3권1호
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• pp.21-24
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• 2012

$5{\alpha}$-Dihydrotestosterone (DHT) is the primary active metabolite of testosterone, catalyzed by $5{\alpha}$-reductase ($5{\alpha}R$) in the skin, prostate, and liver. In this study, the $5{\alpha}R$ activity in rat liver S9 fraction in the presence of a NADPH-generating system was evaluated and compared by gas chromatography-mass spectrometry (GC-MS)-based in vitro assays. Testosterone and a $5{\alpha}R$ inhibitor, finasteride, were added to the S9 fractions and incubated at $37^{\circ}C$ for 1 h. Both testosterone and DHT were quantitatively measured and compared with two different GC-MS-based steroid profiling techniques. DHT was not detected by conventional GC-MS analysis in the absence of finasteride when the concentration of testosterone in the S9 fraction was less than $0.2{\mu}M$, whereas the isotope-dilution GC-MS (GC-IDMS) system was able to evaluate the $5{\alpha}R$ activity. Because the S9 fraction contains more reactive enzymes and is easier to collect from tissues compared with a microsomal solution, the combination of the S9 fraction and GC-IDMS technique may be a promising assay for evaluating the $5{\alpha}R$ activity in large-scale clinical studies.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.190-196
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• 2008

Deoxypodophyllotoxin (DPT) is a medicinal herb product isolated from Anthriscus sylvestris. DPT possesses beneficial activities in regulating immediate-type allergic reaction and anti-inflammatory activity through the dual inhibition of cyclooxygenase-2 and 5-lipoxygenase. In the present study, the metabolism of DPT was further characterized in rat liver microsomes isolated from male Sprague Dawley rats. The metabolism of DPT was NADPH-dependent. In addition, when liver microsomes were incubated with SKF-525A, a well-known CYP inhibitor, in the presence of $\beta$-NADPH, the metabolism of DPT was significantly inhibited. Using enriched rat liver microsomes, the anticipated isoforms of cytochrome P450s (CYPs) in the metabolism of DPT were partially characterized. Phenobarbital-induced microsomes increased in the formation of metabolite M1. The metabolite M3 was only produced in the enriched microsomes isolated from dexamethasone-treated rats. The results indicated that the metabolism of DPT would be CYP-dependent and that CYP2B and CYP3A might be important in the metabolism of DPT in rats.

• Journal of Food Hygiene and Safety
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• 제13권3호
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• pp.258-267
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• 1998

The acetaminophen (AP AP), an antipyretic and analgesic agent, induces the hepatotoxicity by increasing influx of calcium and destabilizing the cellular membrane which can be caused by N-acetyl-p-benzoquinoneimine generated by cytochrome P-450 (CYF-450) when it is overdosed. Diltiazem (DIL), a calcium channel blocking agent, has been known to suppress the CYF-450 activities. To study the effect of DIL in APAP treated rats, the serum biotransformational enzyme analyses and the liver histopathologic examination were conducted on the rats which had been administered DIL at 3, 6, 9 and 12 hours after the 3,000 mg/kg of APAP administration. Following a single dose of DIL administered 12 hours after AP AP administration, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, malondialdehyde and calcium contents of liver and microsome were significantly reduced. Glutathione S-transferase (GST) activity was significantly increased. Histopathologic studies showed that DIL had prevented the development of centrilobular necrosis induced by AP AP in liver tissue. Our results suggested that diltiazem could inhibit the formation of free radical and the influx of calcium and could increase GST activity. Therefore, diltiazem can be administered at the time of 12 hours after overdosed AP AP to diminish the liver damage.

• Applied Biological Chemistry
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• 제36권5호
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• pp.326-331
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• 1993

Three antioxidants were isolated: (-)-epigallocatechin and (-)-epigallo catechin gallate from Theae Folium generally called green tea, and gallic acid from Moutan Cortex. They inhibited $Fe^{3+}-ADP/ascorbate-induced$ lipid peroxidation in rat liver microsomal fraction, showing $IC_{50}$, the concentration of antioxidants which is required to inhibit 50% of the peroxidation for microsomal membranes at 1 mg protein/ml, to be $0.2\;{\mu}g/ml$, $0.4\;{\mu}g/ml$ and $2.5\;{\mu}g/ml$, respectively.

• Journal of the Korean Society of Food Science and Nutrition
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• 제25권1호
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• pp.21-26
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• 1996

본 연구는 streptozotocin 유발 당뇨쥐에서의 MFO계활성 변화 및 이에 지질과산화를 관찰하고자 체중이 140kg 내외의 Sprague-Dawley 종 흰쥐 숫컷을 대조군과 당뇨 유발 시험군으로 나누어 4주간 사육하였다. 당뇨군은 STZ로 당뇨를 유발시켰으며 당뇨 유발 6일후 쥐를 희생기켜 간조직 및 폐조직 microsome 중의 cytochrome $P_{450}$ 및 cytochrome $b_[5}$ 함량과 NADPH-cytochrome $P_{450}$ reductase 활성도를 측정하고 아울러 microsome내의 지질과산화물을 측정하여 다음과 같은 결과를 얻었다. 실험군간에 식이 섭취량은 차이가 없었으나, 체중 증가량과 식이 효율은 당뇨군이 STZ군에 비해 현저하게 감소하였다. 간장 및 폐조직의 무게는 대조군과 당뇨군간에 유의적인 차이는 없었다. 간조직 및 GP조직 중의 cytochrome $P_{450}$ 함량은 대조군에 비해 당뇨군이 150%, 175%씩 증가하였다. 간조직 및 폐조직 중의 cytochrome $b_{5}$은 대조군에 비해 당뇨군이 53%,116%씩 각각 증가하였다. 간조직에서의 NADPH-cytochrome $P_{450}$ reductase 활성은 당뇨군이 대조군에 비해 46% 증가하였으며, 폐조직에서는 75%증가하였다. 지질과산화물가는 당뇨군이 대조군에 비해 간족에서는 약 95% 높았으며 폐조직에서는 73%높았다. 이상의 결과에서 STZ 유발 당뇨쥐에서는 MFO system의 활성도가 대조군에 비해 현저하게 증가되고 지질과산화반응이 같으 srudgid이 촉진되었으며 폐조직에서도 간조직에서와 비슷한 경향이었다. 이러한 것은 당뇨군에서는 MFO system의 활성증가로 free radical 생성이 증가되고 그 결과 지질과산화가 촉진되었다고 볼 수 있다.

• The Korean Journal of Mycology
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• 제26권1호통권84호
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• pp.69-77
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• 1998

Antioxidant activities of 80% ethanol extracts of 63 species of mushroom fruiting bodies were investigated. The ethanol extracts from Daedalea dickinsii, Armillariella mellea, and Fomitella fraxinea showed markedly inhibition on lipid peroxidation in rat liver microsome. The extracts from Daedaleopsis tricolor, Trametes suaveolens, Armillariella mellea, Trichaptium abietinum, Daedalea dickinsii, Fomitella fraxinea, Tylophilus neofelleus, Boletellus obscurecoccineus, and Xerocomus subtomentosus significantly inhibited the hepatic aldehyde oxidase activity, and the extracts from Daedaleopsis tricolor, Armillariella mellea, Daedalea dickinsii, and Fomitella fraxinea slightly stimulated the hepatic SOD activity. These results suggest that Daedalea dickinsii, Armillariella mellea, and Fomitella fraxinea contain the bioactive substances for natural antioxidant and may be useful for development of antioxidant from mushrooms.

• Journal of Nutrition and Health
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• 제23권6호
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• pp.434-442
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• 1990

A new HPLC method for determining malonaldehyde content in lipid peroxidation systems was developed and antioxidant activities of $\alpha$-, $\beta$- carotene, lutein and lycopene were compared by a newly developed HPLC analysis and by TBA value. In addition, malonaldehyde forming ability of rat liver microsome was determined depending on thawing numbers. As results, malonaldehyde was eluted at a retention o f5.60 min and showed a linear relationship between peak area and concentration in standard curve. The MA content of microsome decreased with thawing numbers possible by destruction of cellular membranes. Lycopene, lutein and $\alpha$-carotene showed stronger antioxidant activities than $\beta$-carotene of DL-$\alpha$-tocopherol both in Fe+3-ADP/NADPH and in paraquat/NADPH system. The inhibitory effects of carotenoids and DL-$\alpha$-tocopherol on Fe+3-ADP/NADPH lipid peroxidation system was similar by TBA value and by the HPLC analysis for malonaldehyde.

• Food Science and Preservation
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• 제8권2호
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• pp.231-238
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• 2001

The concentrations of total polyohenolic compound from extract of Paulownia tomentosa Stued. were water-soluble extract 7.98%, methanol extract 12.30% and ethanol extract 11.63%. The free radical scavenger activities of three extracts at the levels of 0.5% were higher than that of BHT(butylated hydroxytoluene). In antioxidative activities measured the concentrations of TBARS(thiobabituric acid reactive substances) in tissues microsome induced with Fe$\^$++/ascorbate, the water-soluble extract was errdctively suppressed in liver and spleen. In antioxidative activities determined by thiocyanate method against lipid peroxidation using linoleic acid, the methanol extract showed the higher compared with other extracts, but BHT showed the highest antioxidative activity. These results suggest that fruit extracts of Paulownia tomentosa Stued. showed to have relatively high concentrations of polyphenolic compounds and antioxidative activities.

• Journal of Pharmaceutical Investigation
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• 제10권3호
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• pp.20-26
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• 1980

The purpose of this paper was to study the effect of sulpyrin on the absorption, excretion, metabolism, and protein binding of ampicillin in the small intestine of the rats and rabbits. The results are as follows; The absorption of ampicillin in small intestine of rats was increased by the combination of sulpyrin and ampicillin. The blood level of ampicillin in rabbits was elevated by oral administration of sulpyrin. The bioavailability of ampicillin was increased by simultaneous administration of sulpyrin and ampicillin. The urinary excretion of ampicillin was slightly decreased by combined administration of sulpyrin. The blood level of ampicillin was decreased and the urinary excretion was increased by long term administration of sulpyrin. On the other hand, metabolising enzyme of ampicillin was influenced by long term administration of sulpyrin. Protein binding rate of ampicillin was decreased by combination of sulpyrin as compared with control.

• Proceedings of the Korean Society of Applied Pharmacology
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.341-341
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• 1994

생체막의 주요 구성성분인 인지질의 2번 위치에 결합한 불포화지방산은 각종 전이금속이나 각종 활성산소들의 공격을 쉽게 받아 지질과산화반응이 일어나서 생체에 유독한 화합물을 생성하게 된다. 생체는 이러한 기구의 해독을 위하여 크게 2가지 방어기전을 갖고 있다. 즉 Vitamin- C, $\alpha$-tocopherol, flavonoid, SOD, catalase 등과 같이 생성된 활성산소를 제거시키는 기구와. 활성산소에 의해 생성된 과산화물을 제거시키는 기구로 glutathione peroxidase (GPX)가 알려졌으며 GPX에 의해 독성이 낮은 수산화물까지 환원시키는 기구가 보고되었다. 그러나 인지질의 과산화물 그대로는 GPX의 기질이 쥘수 없으므로, 산화된 지방산을 절단하는 효소에 대한 기구의 해석이 요구되고 있다. 최근 여러질병에 관련되어 있는 인지질 2번위치의 지방산을 분해하는 phospholipase $A_2$ (PLA$_2$)가 과산화지질의 분해에 관여한다는 주장이 제기되었다. 따라서 본 연구에서는 rat liver microsome에 $CCl_4$투여로 일어나는 과산화반응에 있어서 PLA$_2$의 역할을 규명하기 위하여 본 실험을 행하였다.