• 한국임상약학회지
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• 제9권1호
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• pp.55-61
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• 1999

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride treatment when aminophylline (8 mg/kg as theophylline, i.v.) was injected. The concentrations of theophylline and its major metabolite (1,3-dimethyluric acid) in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric acid from theophylline in microsomes was determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to $17\%$ of the control value while AUC (area under the plasma concentration-time curve) and $(t_{1/2})_{\beta}$ were increased to about 6 fold and 10 fold, respectively. The formation of 1,3-dimethyluric acid was decreased to $33-41\%$ of the control value in microsomes of cirrhotic rat liver. From these results, it can be concluded that in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride the total body clearance of theophylline is markedly reduced due to a reduced hepatic metabolism.

• Archives of Pharmacal Research
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• 제16권2호
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• pp.89-93
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• 1993

Incubation of $S(-)-^3H$-nicotine with rabbit lung microsomes in the presence of dioxygen and NADPH results in the formation of metabolities that bind covalently to microsomal macro-molecules. The addition of cytochrome P-450 monooxygenase inhibitors, $\alpha$-methylbenzyl ami-nobenzotriazole and aroclor 1260, inhibited both (S)-nicotine metabolism and covalent binding. The relative rates of oxidation of nicotine $\Delta^{1',5'}$ iminium ion to continine indicates that lung $100,000\times{g}$ supematant catalyzed this oxidation approximately 18 times slower than that of liver system based on mg of protein, and increased covalent interactions. Since than that of liver system based on mg of protein, nd increased covalent interactions. Since the activity of lung iminium oxidase appears much lowr than the liver, it is tempting to speculate that localized concentrations of nicotine $\Delta^{1',5'}$ iminium ion in the lung will survive for a longer period of time. These results support that cytochrome P-450 catalyzed oxidation of nicotine leads to the formation of reactive nad electrophilic intemediates capable of chemical interactions with biomacromolecules.

• Mass Spectrometry Letters
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• 제13권4호
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• pp.152-157
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• 2022

Schisandra chinensis and its fruits have been used as a traditional herbal medicine to treat liver dysfunction, fatigue, and chronic coughs. Several in vitro and in vivo studies suggested that dibenzocyclooctadiene lignans present in Schisandra fruits strongly inhibit CYP3A4 activity. However, reports on the inhibitory potential of dietary Schisandra supplements against CYP3A activity are limited despite their increasing consumption as dietary supplements. In this study, we evaluated the CYP3A-inhibitory potential of four dietary Schisandra supplements in human liver microsomes. At a concentration of 0.05 mg/mL, Schisandra supplements from Nature's Way, Swanson, Planetary Herbals, and Only Natural inhibited CYP3A activity by 93.9, 70.8, 33.6, and 24.8%, respectively. Nature's Way, which exhibited the strongest inhibition against CYP3A, had the highest contents of gomisin B and gomisin C, which potently inhibit CYP3A activity. The in vivo pharmacokinetics of this product should be examined to determine whether the clinical relevance of inhibiting CYP3A activity by dietary Schisandra supplementation.

• 대한약리학회지
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• 제16권2호
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• pp.45-53
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• 1980

Lipid peroxidation in vitro has been identified as a basic deteriorative reaction in cellular mechanism of aging processes, such as air pollution oxidant damage to cell and to the lung, chlorinated hydrocarbon hepatotoxicity. Many experimental evidences were reported by several investigators that lipid peroxidation could be one of the principle causes for the hepatotoxicity produced by $CCl_4$. It is now reasonably established that $CCl_4$ is activated to a free radical in vivo, that lipid peroxidation occurs very quickly in microsomes prepared from damaged livers, that the peroxidation is associated with loss of enzyme activity of microsomes, and that various antioxidants can protect animals against the hepatotoxic effect of $CCl_4$. Recent studies have drawn attention to some other feature of microsomal lipid peroxidation. Incubation of liver microsomes in the presence of NADPH has led to a loss of cytochrome $P_{450}$. However, the presence of an antioxidant prevented lipid peroxidation and preserved cytochrome $P_{450}$. Decrease of cytochrome $P_{450}$ in microsomes under in vitro incubation can be enhanced by $CCl_4 and these changes were parallel to a loss of microsomal polyunsaturated fatty acid and formation of malonaldehyde. The primary purpose of this experiment was to study the effect of riboflavin tetrabutylate on lipid peroxidation, specially, the relationship between lipid peroxidation and drug metabolizing enzyme system which is located in smooth endoplasmic recticulum as well as the effect of ritoflavin tetrabutylate on drug metabolizing enzyme system of animal treated with $CCl_4$. Albino rats were used for experimental animal. In order to induce drug metabolizing enzyme system, phenobarbital was injected intraperitoneally. $CCl_$ and riboflavin tetrabutylate were given intraperitoneally as solution in olive oil. Microsomal fraction was isolated from liver of animals and TBA value as well as the activity of drug metabolizing enzyme were measured in the microsomal fractions. The results are summerized as following. 1) The secobarbital induced sleeping time of $CCl_4$ treated rat was about 2 times longer than that of the control group. However, the pretreatment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to $CCl_4$ treatment. Furthermore TBA value was significantly increased in $CCl_4$ treated rat in comparison to control group tut the increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. On the other hand, the activity of hepatic drug metabolizing enzyme was decreased in $CCl_4$ group, however, the pretreatment with riboflavin tetrabutylate also prevented the decrease of the enzyme activity caused by $CCl_4$. 2) The effect of riboflavin tetrabutylate on TBA value and the activity of drug metabolizing enzyme in vitro was similar to in vivo results. Incubation of liver microsome from rat in the presence of $CCl_4$, $Fe^{++}$, or ascorbic acid has led to the marked increase of TBA value, however, the addition of riboflavin tetrabutylate in incubation mixture prevented significantly the increase of TBA value, suggesting the inhibition of lipid peroxidation. In accordance with TBA value, the activity of drug metabolizing enzyme was inhibited in the presence of $CCl_4$, $Fe^{++}$, ascorbic acid but the addition of riboflavin tetrabutylate protected the loss of the enzyme activity in microsome under in vitro incubation.

• 한국수산과학회지
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• 제32권6호
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• pp.758-763
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• 1999

다시마 (Laminaria japonica) 추출물 건조분말 $4.0\%$ 첨가사료(Dasi-Ex)와 여기에 후코이단 $1.0\%,\;2.0\%,\;3.0\%$ 첨가사료 (Fuco-I, II, III group)를 SD계 랫트에 45일간 투석하여 노화억제작용에 미치는 영향을 평가하였다. Dasi-Ex 및 Fuco-I, II, III 투여그룹의 신장 mitochondria 및 microsome의 $\cdot$OH의 생성은 대조그룹 대비 각각 $10\~15\%$ 및 $15\~30\%$ 의 유의적인 억제효과가 인정되었다. Dasi-Ex 및 Fuco-I, II, III 투여그룹의 신장 microsome의 $H_2O_2$의 생성도 대조그룹 대비 $10\~15\%$의 유의적인 억제효과가 인정되었다. 따라서 신장의$\cdot$OH 및 $H_2O_2$의 생성 억제효과는 다시마추출물보다는 후코이단의 투여가 효과적일 뿐만 아니라 후코이단 첨가량에 따른 용량 의존성도 인정되었다. 신장 mitochondria에서 Dasi-Ex 및 Fuco-I 투여그룹의 BOR생성은 전혀 유의적인 효과가 인정할 수 없었지만, Fuco-II 및 III투여그룹의 BOR 생성은 $12\~16\%$의 유의적인 억제효과가 인정되었다. 신장 microsome에서는 Dasi-Ex 및 Fuco-I, II, III 투여그룹의 BOR의 생성이 $15\~25\%$의 유의적인 억제효과가 인정되었을 뿐만 아니라 후코이단의 첨가량에 따른 용량 의존성이 인정되었다. 또한 신장 mitochondria에서 Dasi-Ex 투여그룹의 IOR의 생성은 유의적인 억제효과가 인정할 수 없었지만, Fuco-I, II, III 투여그룹의 TOR 생성은 $10\~15\%$의 유의적인 억제효과가 인정되었다. 신장 microsome에서는 Fuco-II 및 III 투여그룹만이 $13\~14\%$의 유의적인 IOR의 생성 억제효과가 인정되었다. 신장 mitochondria 및 microsome분획중의 LPO의 생성은 Fuco-II, III의 투여부터 각각 $15\%$ 및 $15\~25\%$ 정도의 효과적인 억제효과가 인정되었다. mitochondria 획분에서 Dasi-Ex 및 Fuco-I, II, III 투여그룹의 유동성은 대조그룹의 유동성 대비 $20\~35\%$의 유의적인 유동성의 증가효과가 인정되었다. microsome 분획에서 Basi-Ex 및 Fuco-I, II, III 투여그룹의 유동성은 대조그룹 대비 $17\~24\%$의 유의적인 증가효과가 인정 되었다. 따라서 다시마 추출물 (Dasi-Ex) 단독 투여보다 후코이단 (Fuco-I, II, III)의 투여가 생체 방어효소의 활성을 촉진할 뿐만 아니라 활성산소의 공격으로부터 신장의 기능을 효과적으로 보호할 수 있을 것으로 기대된다.

• 생명과학회지
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• 제9권4호
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• pp.439-452
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• 1999

This study was designed to investigate the effects of sea tangle (Laminaria japonica) extract and fucoidan components on anti-aging action. Sprague-Dawley(SD) male rats (210$\pm$5g) were fed experimental diets Dasi-Ex group: sea tangle extract powder of 4.0% added to control diet; Fuco-I, II and III groups: funcoidan powder of 1, 2 and 3% added to Dasi-Ex group for 45 days. Hydroxyl radical (.OH) formations were significantly inhibited (10-20% and 25-30%) in serum and brain mitochondria of Dasi-Ex and Fuco-I, II and III groups compared with control group. Significant differences in .OH formations of brain mitochondria in Dasi-Ex and Fuco-I groups could not be obtained, but.OH formations of brain microsomes resulted in a significant decrease (15-20%) in Fuco-II and III groups compared with control group. Basal oxygen radical (BOR) formations were significantly decreased about 10% and 13-15% in brain mitochondria of Dasi-Ex and Fuco-I group, and Fuco-II, III groups, and also decreased about 10% and 15-20% in brain microsomes of Dasi-Ex and Fuco-I groups, and Fuco-II, III groups. LPO levels of brain mitochondria and microsomes were significantly inhibited about 10% in Dasi-Ex and Fuco-I, II groups and 15% in Fuco-III groups. Oxidized proteins (>C=O) were significantly inhibited about 10% in serum of Dasi-Ex and Fuco-I, II, III groups and brain mitochondria of Dasi-Ex group, while remarkably inhibited (30~35%) in brain mitochondria of Fuco-I, II and III groups. Nitric oxide (NO) levels were significantly inhibited (12~15%) in serum of Fuco-I, II and III groups, but there no significant difference in serum NO levels of Dasi-Ex group. Superoxide dismutase (SOD) activities were remarkably increased (30~ 60%) in serum of Fuco-I, II and III groups, but there were no significant differences in SOD activities in serum of Dasi-Ex group. Catalase (CAT) activities were significantly increased about 20% in serum of Dasi-Ex and Fuco-I, II, III groups. Mn-SOD activities in brain mitochondria were significantly increased about 17% in Dasi-Ex group, while remarkably increased 26~36% in Fuco-I, II, III groups. Cu,Zn-SOD activities in brain cytosol were dose-dependently of fucoidan increased 10%, 12% and 18%, respectively, compared with control group. These results suggest that anti-aging effects of fucoidan may play a pivotal role in attenuating a various age-related changes such as chronic degenerative disease and senile dementia.

• 생명과학회지
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• 제13권5호
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• pp.692-698
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• 2003

뇌 세포막 유동성의 촉진 및 LPO생성의 억제효과는 중풍 등 뇌혈관질환을 억제할 수 있을 뿐만 아니라 혈관성치매의 예방에도 크게 기여할 것으로 기대된다[26,18]. 따라서 솔잎 EtOAc획분을 하루 25, 50, 100 mg/kg BW로써 SD계 랫트에 45일동안 투여하여 뇌조직중의 세포막 유동성 (membrane fluidity : MF), 기초 및 유도활성산소(BOR 및 IOR), 산화적 스트레스로서 과산화지질(lipid peroxide : LPO) 및 산화단백질(oxidized protein : OP), 그리고 리포푸신(lipofuscin : LF)의 축적에 미치는 영향을 평가하여 보았다. 솔잎 EtOAc획분의 투여에 의하여 뇌조직의 mitochondria 및 microsome획분에서 용량의존적으로 MF가 증가효과가 나타났지만, EtOAc-100 투여그룹의 mitochondria 획분에서만 약 10%의 유의적인 MF의 증가효과가 인정되었다. 뇌조직의 mitochondria에서 기초 및 유도활성산소로서 BOR 및 IOR의 생성은 EtOAc-50 및 EtOAc-100투여그룹에서 각각 9.2∼10.2% 및 17.1∼24.0%의 유의적인 억제효과가 인정되었고, microsomes에서 BOR 및 IOR의 생성은 EtOAc-50및 EtOAc-100투여그룹에서 각각 11.6∼16.6% 및 12.1∼16.1%의 유의적인 억제효과가 인정되었다. 산화적 스트레스에 미치는 영향은 mitochondria 및 microsomes획분에서 EtOAc-50 및 EtOAc-100투여그룹에서 각각 8.5∼12.0% 및 11.6∼18.5%의 유의적인 LPO의 생성 억제효과가 인정되었지만, 뇌조직의 두 획분에서 OP의 생성은 EtOAc획분의 용량의존적으로 억제되었지만, 유의성은 인정할 수 없었다. 또한 뇌조직에서 LF의 축적도 EtOAc획분의 용량 의존적으로 억제효과가 나타났지만, 유의성은 인정할 수 없었다. 이상의 결과에서 평가하여 볼 때 솔잎 EtOAc획분의 투여는 뇌조직의 유동성을 촉진하고 LPO의 생성을 효과적으로 억제할 수 있지만, 현재의 투여농도에서는 OP 및 LF의 생성을 방지할 수 없을 것으로 생각된다.

• 한국식품과학회지
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• 제28권6호
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• pp.1157-1163
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• 1996

방아의 ether추출물을 중성, 페놀성, 산성 및 염기성 획분으로 분획한 다음 그들의 항산화 활성을 수소 공여능, 과산화물가, TBA가 및 흰쥐 간 microsome을 이용한 비효소적 지질 과산화 억제 활성 등으로 측정하고, 항산화 활성이 비교적 높게 나타나는 페놀성 획분과 중성 획분을 다시 소획분으로 분획한 다음 그중에서 항산화 활성이 강한 소획분성분을 GC/MS 및 NMR로 분석, 동정하였다. 페놀성 획분은 DPPH에 의한 수소 공여능, POV, TBA가 및 흰쥐 간 microsome의 지질 과산화 억제 활성 등 모두에서 높게 나타났으며, 중성 획분은 흰쥐 간 microsome의 지질 과산화 억제 활성에서 높게 나타났다. 페놀성 획분을 소획분으로 분획하였을 때 소획분 P-1, P-2 및 P-3에서 항산화 활성이 강하였으며, 특히 P-2는 합성 항산화제인 BHT나 천연 항산화물질로 알려져 있는 caffeic acid보다도 강하였다. 소획분 P-2를 TMS 유도체로 만들어 GC로 분석하였을 때 major peak 성분인 Peak I, II, III 및 IV 모두 TMS m/z 73를 base peak로 가지고 있어 4개의 peak 모두 -OH, -COOH기를 가지고 있는 것으로 확인할 수 있었다. 중성 획분의 소획분 중에는 N-2에서 강한 활성을 나타내었고 소획분 N-2의 주성분을GC/MS 및 NMR로 분석 한 결과 estragole로 확인되었다. Estragole의 흰쥐 간 microsome의 지질 과산화 50% 억제 농도는 $20{\sim}50\;{\mu}g/ml$로서 BHT보다는 약하였으니 caffeic acid, gallic acid와는 비슷한 수준의 항산화 활성을 나타내었다.

• Archives of Pharmacal Research
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• 제7권1호
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• pp.63-64
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• 1984

This major sites of liquidperoxidation-damage within the cell are at biomembrances, especially those of subcellular organells such as mitochondria and microsomes whose membranes contain relatively large amount of polyunsaturated fatty acids. Mitochondria are the power plants of eukaryotic cells. Hence their damage by liquid peroxidation can profoundly affect cellular function.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1998년도 학술발표회
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• pp.29-29
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• 1998

Previously, we reported two types of vanadate-sensitive ATPases in the micro somes of tracheal epithelial cells, a high-affinity one and a low-affinity one. The low affinity vanadate-sensitive (LAVS) ATPase was sensitive to thapsigargin and cyclopiazonic acid, specific antagonists of ER-type Ca$\^$2＋/-ATPase, and mediated microsomal $\^$45/Ca$\^$2+/ uptake, implying that the LAVS-ATPase is an ER/SR-type Ca$\^$2+/-ATPase.(omitted)