• Bulletin of the Korean Chemical Society
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• 제24권5호
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• pp.559-565
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• 2003

An analytical method the determination of benzo(a)pyrene (BaP) and its hydroxylated metabolites, 1-hydroxybenzo(a)pyrene (1-OHBaP), 3-hydroxybenzo(a)pyrene (3-OHBaP), benzo(a)pyrene-4,5-dihydrodiol (4,5-diolBaP) and benzo(a)pyrene-7,8-dihydrodiol (7,8-diolBaP), in rat urine and plasma has been developed by HPLC/FLD and GC/MS. The derivatization with alkyl iodide was employed to improve the resolution and the detection of two mono hydroxylated metabolites, 1-OHBaP and 3-OHBaP, in LC and GC. BaP and its four metabolites in spiked urine were successfully separated by gradient elution on reverse phase ODS $C_{18}$ column (4.6 mm I.D., 100 mm length, particle size 5 ㎛) using a binary mixture of MeOH/H₂O (85/15, v/v) as mobile phase after ethylation at 90 ℃ for 10 min. The extraction recoveries of BaP and its metabolites in spiked samples with liquid-liquid extraction, which was better than solid phase extraction, were in the range of 90.3- 101.6% in n-hexane for urine and 95.7-106.3% in acetone for plasma, respectively. The calibration curves has shown good linearity with the correlation coefficients (R²) varying from 0.992 to 1.000 for urine and from 0.996 to 1.000 for plasma, respectively. The detection limits of all analytes were obtained in the range of 0.01-0.1 ng/mL for urine and 0.1-0.4 ng/mL for plasma, respectively. The metabolites of BaP were excreted as mono hydroxy and dihydrodiol forms after intraperitoneal injection of 20 mg/kg of BaP to rats. The total amounts of BaP and four metabolites excreted in dosed rat urine were 3.79 ng over the 0-96 hr period from adminstration and the excretional recovery was less than 0.065% of the injection amounts of BaP. The proposed method was successfully applied to the determination of BaP and its hydroxylated metabolites in rat urine and plasma for the pharmacokinetic studies.

• Journal of Pharmaceutical Investigation
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• 제22권4호
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• pp.317-321
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• 1992

A high-performance liquid chromatographic (HPLC) method was developed for the determination of diltiazem (DTZ) and its major metabolite, deacetyldiltiazem (DAD), in rat plasma. DTZ, DAD and imipramine, the internal standard, were selectively fractionated from plasma on a $C_{18}$ reversedphase column $({\mu}-Bondapak,\;10\;{\mu}m\;silica,\;300{\times}3.9\;mm\;ID)$. The composition of the mobile phase was methanol: acetonitrile: 0.04 M ammonium bromide: triethylamine (40:24:36:0.06 in volume). The pH of the mobile phase of their method was lowered to 6.4. The eluents from the column were detected for DTZ and DAD using a UV detector at 237 nm. The recovery was >85% for DTZ and DAD, and average intra-day and inter-day coefficients of variation were <6% for DTZ and DAD at the concentration ranges of 20-1000 ng/ml. Detection limit of DTZ and DAD in plasma was 20 ng/ml with signal-to-noise ratio of 3. This method would be applicable to practical pharmacokinetic studies without detriment to the HPLC column.

• 대한한의학회지
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• 제16권2호
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• pp.433-446
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• 1995

The present study was carried out to investigate the effect of water extract and 70% ethanol extract from Gastrodiae Rhizoma on cardiovascular activities and plasma levels of catecholamines in unanaesthetized spontaneously hypertensive rats. The depressor response in SHR was observed during three to six hour period after an oral administration of water extract from Gastrodiae Rhizoma(GR). There was a statistically significant correlation between the magnitude of the depressor response induced by an oral administration of water extract from GR and the initial control blood pressure level. The increase in blood pressure induced by norepinephrine was less in Wistar rat treated with GR water extract than those without GR extract. No significant change in heart rate was observed in SHR receiving either water extract or ethanol extract from GR. Associated with the depressor response, there was a concomitant reduction in plasma levels of norepinephrine in SHR at 4 hour after an oral administration of water extract from GR. Plasma levels of norepinephrine and epinephrine were decreased slightly at 2 hour after an oral administration of ethanol extract from GR. These results suggest that the depressor effect of water extract from GR may be due, in part, to a decreased sympathoadrenal activity.

• Bulletin of the Korean Chemical Society
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• 제33권7호
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• pp.2163-2167
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• 2012

A rapid, specific, and reliable LC-MS/MS-based bioanalytical method was developed and validated in rat plasma for the simultaneous quantitation of amitriptyline and its metabolite nortriptyline. Chromatographic separation of these analytes was achieved on a Gemini C18 column ($50{\times}4.60mm$, $5{\mu}m$) using reversed-phase chromatography. The mobile phase was an isocratic solvent system consisting of 1% formic acid in water and methanol (10:90, v/v), at a flow rate of 0.2 mL/min. The analytical range was set as 0.1-500 ng/mL for amitriptyline and 0.08-500 ng/mL for nortriptyline using a $200{\mu}L$ plasma sample. The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. The validated method was successfully applied to a pharmacokinetic study in six rats after oral administration of amitriptyline (15 mg/kg). This method allows laboratory scientists to rapidly determine amitriptyline and nortriptyline concentrations in plasma.

• Preventive Nutrition and Food Science
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• 제3권1호
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• pp.56-61
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• 1998

This study was conducted to investigate the effect of dietary supplementation of vitamin A on the membrane property and ultrastructure in ethanol-administered rat livers. Male Sprague-Dawley rats weighing of 130 ~150g were fed with experimental diets for 7 weeks. The diets contained different types of vitamin A which were $\beta$-carotene, retinyl acetate and retinoic acid. After feeding theexperimental diets for 7 weeks, a dose of 3.0g ethanol (30%, W/V)/kg B.W was injected to rats intraperitoneally. Control rats received 0.9% saline containing isocaloric sucrose instead of ethanol. Plasma membrane fluidity of liver decreased in rats fed with vitamin a -Deficient diet with ethanol as compared to that of control rats. Fluidity change of liver plasma membrane that ethanol had induced was influenced by dietary supplementation of vitamin A, but not influenced by the type of supplemented vitamin. A . The ultrastructural changed of hepatic mitrochondria were observed in some rats such as vitamin A-deficient rats with ethanol. Inadequate consumptionof vitamin A contributed to ultrastructural changes such as swelled mitochondria occurred by ethanol-induced hepatotoxicity. Although accurate mechanism involved in the plasma membrane-stabilizing effect of vitamin A is still unclear, dietary supplementation of vitamin A such as retinyl acetate is neede to modulate this change. The direct involvement of membrane property on the cell damage caused by ethanol treatment remains to be established.

• Journal of Nutrition and Health
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• 제33권5호
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• pp.502-506
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• 2000

Effects of powdered siho(bupleuri radix) on serum and liver lipid composition and antioxidative capacity were investigated in rat fed high oxidized fat. Sixty male Sprague-Dawley rats weighing 161.25$\pm$2.51g were blocked into four groups according to body weight and raised seven weeks with basal diet(normal group), basal diet and 10% oxidized fat(control group), basal diet, 10% oxidized fat and 2% powdered siho(2% powdered siho group) and basal diet, 10% oxidized fat and 3% powdered siho(3% powdered siho group). Feed intake, body weight gain and feed efficiency were not significantly different among oxidized fat diet groups. The values of total cholesterol and triglyceride in plasma and liver showed no significantly different(p>0.05) in the oxidized fat diet groups. Plasma HDL-cholesterol showed atendency to increase in powdered siho diet groups. The values of thiobarbituric acid in plasma and liver were lower in the powdered siho diet groups than control group. Plasma GOT and GPT activity showed a tendence to decrease in powdered siho groups. Liver glutathione peroxidase activity showed a tendence to increase in powdered siho diet groups. Thus, it seems that powdered siho had some antioxidative elements.

• The Korean Journal of Physiology and Pharmacology
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• 제20권6호
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• pp.565-571
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• 2016

Paeoniflorin (PAE) is the most abundant compound in Xuebijing injection widely used to treat sepsis. We aimed to investigate effect of PAE on expression of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in a rat model of sepsis. Wistar rats were divided into Normal, Model, and PAE groups (n=20 each). Endotoxin was administrated at 5 mg/ml/kg in Model and PAE rats to establish rat sepsis model. 1 h after endotoxin administration, PAE was administrated at 4 ml/kg in PAE group once per day for 3 days. Routine blood tests and biochemical indexes were assessed, including aspartate aminotransferase (AST) and creatine kinase-MB (CK-MB). The plasma sTREM-1 level was measured using quantitative ELISA. At the end of experiment, the small intestine, liver, kidney and lung were subjected to pathological examinations. A rat model of sepsis-induced multiple organ dysfunction syndrome (MODS) was established successfully with endotoxin administration (5 mg/ml/kg), evidenced by histo-pathological examinations, routine blood tests and biochemical indexes: platelet count decreased and white blood cell count increased (p<0.05), CK-MB and AST increased (p<0.05). PAE treatment significantly reduced the plasma levels of AST, CK-MB, and sTREM-1, compared to Model group (p<0.05). Meanwhile, sepsis-induced damages in the liver, lung, stomach and intestinal mucosa were also markedly ameliorated by PAE treatment. PAE demonstrated a significantly protective effect in a rat model of sepsis by decreasing plasma sTREM-1 level, reducing inflammation, preventing MODS and protecting organ functions.

• BMB Reports
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• 제40권6호
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• pp.979-985
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• 2007

Induction of growth hormone (GH) by Glycyrrhizae Radix (GR), one of the most popular herbal medicine, and its major ingredients were studied in rat pituitary cells in vitro and in vivo assay. The MeOH extract and the n-hexane (HX) fraction of GR induced rat GH (rGH) release up to 1.89 times ($0.34{\pm}0.04 nM$) and 4.59 times ($0.83{\pm}0.03 nM$), compared to the basal level (p < 0.05). Among many ingredients isolated and purified from GR both glycyrrhetinic acid and glycyrrhizin induced significantly rGH release compared to the control (p < 0.05). After an intravenous injection of rat growth hormone releasing hormone (rGHRH) ($10{\mu}g$/kg) as positive control, in SD rats, $T_{max}$ of plasma rGH level was 10 min, $C_{max}$ was $3.84{\pm}0.01 nM$ (n = 3), and enhanced plasma rGH level returned to the baseline in 90 min. Both $AUC_{0-90}$ (area under the curve) of plasma rGH level after HX fraction and that after rGHRH administration were increased significantly from the basal level, respectively (p < 0.01). In conclusions, HX fraction is the most active fraction of MeOH extract of GR in rGH induction.

• 한국식품과학회지
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• 제37권1호
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• pp.90-94
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• 2005

Quercetin을 50 및 100mg/kg의 용량으로 mouse에 경구투여 후 흡수, 대사 및 조직내 농도를 조사하였으며 일부의 시험은 비교를 위해 rat에서도 수행하였다. Quercetin은 mouse에서 신속히 흡수되어 l시간 후면 최고 혈장내 농도에 도달하였으며 4시간 후에는 현저하게 농도가 감소하였다. 주요 대사체인 isorhamnetin의 혈장내 농도도 신속하게 증가하였으나 quercetin 보다는 높은 농도로 유지되는 시간이 길었다. Rat에서 알려진 현상과 같이 quercetin이나 isorhamnetin 모두 유리상태로 존재하지 않고 대부분 glucuronide/sulfate의 포합체 형태로 존재하였다. Quercetin 및 isorhamnetin의 조직내 농도는 투여 1시간 및 6시간 콩히 간장>신장>비장>혈장의 순이었으며 이 순서는 rat에서도 마찬가지였다. 이 연구결과를 통해 mouse에서 quercetin이 경구투여 후 실제로 흡수되며 사람이나 다른 동물종에서 관찰된 것과 같이 quercetin은 신속하게 전환됨을 관찰하였다. 또한 이 결과는 mouse를 이용한 실험에서 지금까지 규명된 quercetin의 다양한 약리효과를 설명하는 데 필요한 자료의 역할을 할 수 있을 것이다.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.223.1-223.1
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• 2002