• Korean Journal of Clinical Pharmacy
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• v.9 no.1
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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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• v.16 no.2
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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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• v.13 no.4
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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.

• The Korean Journal of Pharmacology
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• v.16 no.2 s.27
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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.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.32 no.6
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• pp.758-763
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• 1999

The protective effects of sea tangle (Laminaria japonica) extract and fucoidan components on the attack of oxygen radicals in kidney were studied, Sprague-Dawley (SD) male rats (210 $\pm$ 5 g) were with fed experimental diets of Dasi-Ex group (sea tangle extract powder of $4.0\%$ added to control diet), Euco-I, II and III groups (fucoidan powder of 1, 2 and $3\%$, respectively, added to Dasi-Ex group) for 45 days, Hydroxyl radical formations were significantly decreased ($10\~15\%$ and $15\~30\%$) in mitochondria and microsomes of Dasi-Ex and Fuco-I, II, III groups compared with control group. Hydrogen peroxide formations were also significantly decreased ($10\~15\%$) in microsomes of Dasi-Ex and Fuco-I, II, III groups compared with control group. Significant differences in mitochondrial basal oxygen radical (BOR) and microsomal induced oxygen radical (IOR) formations of Dasi-Ex and Fuco-I groups could not be obtained, but mitochondrial BOR and microsomal IOR formations were significantly decreased ($12\~15\%$ and $13\~14\%$) in Fuco-II and III groups compared with control group. BOR formations were significantly decreased ($12\~25\%$) in microsomes of Dasi-Ex and Fuco-I, II, III groups, and IOR formations were also significantly decreased ($10\~15\%$) in mitochondria of Fuco-I, II, III groups compared with control group, Significant differences in mitochondrial Mn-SOD activities of Dasi-Ex group could not be obtained, but mitochondrial Mn-SOD activities were dose-dependently increased by $8\%,\;16\%$ and $36\%$ in Fuco-I, II and III groups compared with control group, Mn-SOD activities an microsome were significantly increased about $20\%$ in Dasi-Ex group, while they were remarkably increased about $40\%$ in Fuco-I, II and III groups compared with control group. lipid peroxide contents were significantly decreased about $15\%$ and $15\~25\%$ in mitochondria and microsomes of Fuco-II and III groups. Membrane fluidities resulted in marked increases ($20\~35\%$ and $17\~24\%$) in mitochondria and microsomes of Dasi-Ex and Fuco-I, II and III groups. These results suggest that administrations of fucoidan added to sea tangle may play a pivotal role in attenuating attack of oxygen radicals in kidney.

• Journal of Life Science
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• v.9 no.4
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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.

• Journal of Life Science
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• v.13 no.5
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• pp.692-698
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• 2003

This study was designed to investigate the effects of ethyl acetate (EtOAc) fraction of pine (Pinus densiflora Sieb et Zucc) needle on membrane fluidity (MF), basal and induced oxygen radical (BOR and IOR), lipid peroxide (LPO) and oxidized protein (OP) as a oxidative stress, and lipofuscin (LF) in brain membranes of Sprague-Dawley (SD) rats. Male SD rats were fed basic diets (control) and experimental diets (EtOAc-25, EtOAc-50 and EtOAc-100) for 45 days. MF was significantly increased (about 10%) in mitochondria of EtOAc-100 group. BOR and IOR formations in mitochondria were significantly inhibited (about 9∼10% and 17∼24%, respectively) in EtOAc-50 and EtOAc-100 groups, while BOR and IOR formations in microsomes were significantly inhibited (about 12∼17% and 12∼16%, respectively) in EtOAc-50 and EtOAc-100 groups compared with control group. LPO levels in mitochondria and microsomes were significantly inhibited (about 9∼l2% and 12∼19%, respectively) in EtOAc-50 and EtOAc-100 groups, whereas significant difference between OP or LF levels and control group in these membranes could not be obtained. These results suggest that administrations of ethyl acetate fraction of pine needle may play an effective role in an attenuating an oxidative stress and in increasing membrane fluidity.

• Korean Journal of Food Science and Technology
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• v.28 no.6
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• pp.1157-1163
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• 1996

Bangah, one of the herbs grown in Korea, was investigated for its antioxidant activity. The ether extracts of bangah herb was separated into neutral, phenolic, acidic and basic fractions and further separated into subfractions. Antioxidative activities were measured by hydrogen donating activity (HDA), peroxide value (POV), thiobarbituric acid (TBA) value and inhibition activity against lipid peroxidation of rat liver microsomes, The subfraction components were identified by GC/MS and NMR. Phenolic, though being very small in quantity, showed higher antioxidant activity at all assay system by hydrogen donating activity. POV, TBA value and inhibition activity against lipid peroxidation of rat liver microsomes. Five subfractions(P-1, P-2, P-3, P-4 and P-5) were fractionated from phenolic fraction of bangah herbs, and subfraction P-2 among them showed strong antioxidant activity on a level with BHT or gallic acid at each assay system. Four compounds (peak I, peak II, peak III and peak IV) were isolated by gas chromatogram of TMS derivatives of subfraction P-2 and thes compounds were confirmed to be phenolic substance having -OH and COOH group. There subfractions (N-1, N-2 and N-3) were fractionated from neutral fraction of bangah herbs, and subfraction N-2 among them showed highest antioxidant activity and inhibition activity against lipid peroxidation of rat liver microsomes. Subfraction N-2 was indentified to be estragole by H-NMR spectroscopy.

• Archives of Pharmacal Research
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• v.7 no.1
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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.

• Proceedings of the Korean Biophysical Society Conference
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• 1998.06a
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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)