• Archives of Pharmacal Research
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• v.26 no.1
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• pp.89-94
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• 2003

In vivo clearance of BMS-182874 was primarily due to metabolism via stepwise N-demethylation. Despite in vivo clearance approached ca 50％ of the total liver plasma flow, BMS-182874 was completely bioavailable after oral administration in rats. Saturable first-pass metabolism and the role of extrahepatic tissue were evaluated as possible reasons for complete oral bioavailability despite extensive metabolic clearance. Pharmacokinetic parameters were obtained after an intravenous and a range of oral doses of BMS-182874 in rats. Bile and urine were collected from bile-duct cannulated (BDC) rats and the in vivo metabolic pathways of BMS-182874 were evaluated. Pharmacokinetics of BMS-182874 were also compared in nephrectomized (renally impaired) vs. sham-operated control rats. Oral bioavailability of BMS-182874 averaged 100％, indicating that BMS-182874 was completely absorbed and the first-pass metabolism (liver or intestine) was negligible. The AUC and C/sub max/ values increased dose-proportionally, indicating kinetics were linear within the oral dose range of 13 to 290 mmole/kg. After intravenous administration of BMS-182874 to BDC rats, about 2％ of intact BMS-182874 was recovered in excreta, indicating that BMS-182874 was cleared primarily via metabolism in vivo. The major metabolite circulating in plasma was the mono-N-desmethyl metabolite and the major metabolite recovered in excreta was the di-N-desmethyl metabolite. In vivo clearance of BMS-182874 was significantly reduced in nephrectomized rats. These observations suggest saturable first-pass metabolism is unlikely to be a mechanism for complete oral bioavailability of BMS-182874. Reduced clearance observed in the nephrectomized rats suggests that extrahepatic tissues (e.g., kidneys) may play an important role in the in vivo clearance of xenobiotics that are metabolized via N-demethylation.

• YAKHAK HOEJI
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• v.52 no.2
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• pp.93-100
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• 2008

A liquid chromatographic method with tandom spectrometric detection (LC/MS/MS) for the simultaneous determination of doxifluridine and its active metabolite, 5-fluorouracil (5-FU) was developed over the concentration range of $5{\sim}2000$ ng/ml, respectively. Doxifluridine, 5-FU and internal standard, 5-chlorouracil (5-CU), were extracted from liver and intestine tissue via protein precipitation. Acetonitrile was used as the extraction solvent and the supernatant was evaporated and reconstructed in mobile phase. Optimum chromatographic separation was achieved on a Agilent Zorbax $C_{18}$ ($100\;mm{\times}2.1\;mm$, $3.5\;{\mu}m$) column with mobile phase run in isocratic with methanol : water (20 : 80, v/v). The flow rate was 0.2 ml/min with total cycle time of 5 min. The lower limit of quantification was validated at 5.0 ng/ml of liver and intestine tissue, for both doxifluridine and 5-FU, respectively. The intra-day and inter-day precision and accuracy of quality control (QC) samples were <11% coefficient of variation and <7% relative error from theoretical concentration for both analytes. In addition, the special designed stability study was performed, because the metabolism of doxifluridine occurs spontaneously even in ice bath for monkey liver. The stability of doxifluridine in liver and intestine of monkey and beagle dog was compared. It was found that bioanalytical validation could not be performed for the monkey liver; however, beagle dog's liver has relatively low speed of metabolism compared to monkey liver and instead of monkey liver, beagle dog's liver could be used for the validation. Bioanalytical validation could be performed in monkey intestine. Eventually, this developed method for liver and intestine will be useful in support of the toxicokinetic and pharmacokinetic studies of doxifluridine and 5-FU.

• Journal of the East Asian Society of Dietary Life
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• v.8 no.2
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• pp.93-106
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• 1998

This study was designed to find out the effects on the lipid metabolism of two herbs used in folk treatment in Korea The two herbs were A: Equisetum arvense L. (Seddugi), B: Eunymus alatus Siebold (Hwasalnamoo). The experiment was performed with the male rats of Sprague-Dawley which fed on high calorie and animal fat supplemented diets from which 30% of the total calories can from lard. Experimental groups were divided into standard (ST) and two other(A, B) groups for the each herb. Each of the two experimental groups consisted of three subgroups (I, II, III) according to the three different doses of the folk remedy used, which were five times and ten times the dose commonly used in a folk remedy. During the experimental period, total food intake and body weight gains were measured, and FER, CER, PER were calculated at the same times. Serum levels of triglyceride, total lipid, ttal cholesterol, HDL-cholesterol, and total lipid as well as cholesterol contents of the liver were measured at the time of sacrifice. Epididymal fat pads were weighted and an indes was calculated. The results of the effects on the lipid metabolism were as follows : 1.Total food intake and body weight gains increased in group A & B. 2. The serum levels of the total lipid and triglyceride decreased in AIII, BI and BIII.3. The serum level of cholesterol decreased in group B, while level of HDL-Cholesterol were increased in all groups and most effectively in group B. 4. The contents of total liver lipid increased in groups A&B. cholesterol decreased in groups A&B. In conclusion, effects on the lipid metabolism associated with the kinds of herbs a diet were the increase of body weighta and the decrease of total lipid and cholesterol levels in serum and liver.

• Journal of Nutrition and Health
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• v.32 no.4
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• pp.353-368
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• 1999

This study was performed to investigate the effects of Korean native plant diets on lipid and cadmium (Cd) metabolisms and also antioxidative enzyme activities in rats. Seventy male Sprague-Dawley rats weighing 210.3$\pm$2.7g were blocked into ten groups according to body weight. Rats were raised for four weeks with diets containing 0 or 0.04%(w/w) cadmium chloride and 5%(w/w) plant powder-Ssook(Artemisia princeps var. orientalis HARA), Chamchwi(Aster scaber THUNB), Gomchwi(Lingularia fischeri TUBCZ). or Solbeerum (Portulaca oleracea LINNE). Food intake, weight gain, food efficiency ratio, and weights of liver, kidney, spleen and epididymal fat were significantly lower in Cd-exposed groups, food efficiency ratio, and weights of liver, kidney, spleen and epididymal fat were significanlty lower in Cd-exposed groups. Plasma total lipid level, liver total lipid, cholesterol and triglycerde concentrations, and fecal total lipid, cholesterol and triglyceride excretions were decreased by Cd administration. Total lipid and triglyceride concentration in plasma and liver were lower in Chamchwi groups together with increased fecal total lipid and triglyceride excretions. Cholesterol concentration in plasma and liver were lower in Gomchwi groups with increased fecal cholesterol excretions. Activities of red-blood-cell superoxide dismutase(SOD), and liver catalase, SOD and glutathione peroxidase (GSH-px) were decreased significantly by Cd administration. Thiobarbituric acid reactive substance(TBARS) concentrations of plasma and liver were increased by Cd administration. Thiobarbituric acid reactive substance(TBARS) concentration of plasma and liver were increased by Cd administration. Administration of plant diets decreased plasma and liver catalase, SOD and GSH-px activities in Cd-free diet groups and increased them in Cd-administered groups. Plasma and liver TBARS concentrations were decreased in animals fed plant diets, with Chamchwi showing the most effective antioxidative capacity. The concentration of Cd accumulated in blood and tissue decreased in Cd-exposed groups fed plant diets. Liver Cd concentration were lower in the Chamchwi and Gomchwi groups, and kidney Cd levels were lower in the Ssook and Chamchwi groups. Among them, Chamchwi was the most effective in Cd detoxification. In conclusion, Chamchwi and Gomchwi were effective in lowering tissue lipid levels, with Chamchwi having the greatest antioxidative and detoxifying effects.

• Journal of the Korean Society of Food Culture
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• v.5 no.2
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• pp.259-263
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• 1990

To assess the effects of water extracts in fruits of Omija (Schizandra chinensis Baillon) on alcohol metabolism, rats were orally administrated with alcohol (25% alcohol, 0.75g/200g B.W., 40% alcohol, 0.8g/200g B.W.). The level of metabolites and enzyme activities of the serum and liver were unchanged by the 25% ethanol or 40% ethanol treatment with acute orally administration. Blood alcohol level was markdely decreased by the treatment with water extracts in fruits of Omija. The serum level of Urea nitrogen, Free fatty acid, GPT and LDH were tended to decreased, level of GOT was unchanged. Contents of hepatic microsomal protein, glycogen, pyruvate in the liver were increased by water extracts in fruits of Omija. In conclusion, the present study clearly demonstrates that water extract in fruits of Omija promotes the overall metabolism and detoxication of alcohol.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.3
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• pp.453-459
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• 2000

This study was performed to investigate the effect of dietary crab shell powder on lipid metabolism in diet induced hyperlippidemic rats. Sixteen male Sprague-Dawley rats were divided into two groups and fed 20% (w/w) carb shell powder supplemented diet for 4 weeks. Energy intake and weight gain were lower in experimental group than in control group. Concentrations of plasma triglyceride, total cholesterol, LDL-cholesterol, and atherogenic index (AI) were decreased and concentration of HDL-cholesterol was increased by crab shell powder supplementation. Concentrations of liver total cholesterol and triglyceride were significantly lower in experimental group. The crab shell decreased triglyceride and cholesterol concentration in plasma and liver, and increased bile acid excretion in feces. Therefore, the crab shell powder is assumed to exhibit function of chitin or chitosan that effects on lipid metabolism and cholesterol reabsorption.

• Journal of Life Science
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• v.6 no.3
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• pp.159-164
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• 1996

Effects of 1% dietary orotic acid on triglyceride metabolism were examined in SD-rats and Kud: ddY mice. When rats were fed semisynthetic diet containing 1% orotic acid and n-6 polyunsaturated fatty acid (linoleic acid), the hepared diet. In contrast to rats which respond to orotic acid consumption with increases in hepatic triglyceride content, mice did not so respond. The rats-limiting step in triglyceride synthesis is catalyzed by the enzyme phosphatic acid phosphohydrolase (EC3.1.3.4) which is present in the liver cytosol and microsomes of rats fed oroic acid diet. This finding suggests that the activity of this enzyme may play a tole in the fatty liver formation in rats.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.143-146
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• 2011

Scutellariae Radix is widely used in the traditional herbal medicine for the treatment of fever, cough, dysentery, hepatitis and hypertension in Korea, China and Japan. In this study, we investigated the effects of 70% ethanolic extract of Scutellariae Radix (SRE) on CYP450-mediated drug metabolism in the in vitro systems using human liver microsomes and hepatocytes. The microsomal incubation assay showed that SRE inhibited the drug metabolism reactions catalyzed by CYP1A2, CYP2C8 and CYP2C9 in a dose-dependent manner. In particular, SRE was shown to strongly inhibit the metabolic activity of CYP1A2 with an $IC_{50}$ value of 4.6 ${\mu}g/mL$. When SRE was evaluated for its effect on the induction of CYP450 enzyme activities in cryopreserved human hepatocytes, SRE did not exhibit any effect.

• Journal of Nutrition and Health
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• v.26 no.6
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• pp.680-691
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• 1993

Rats were fed for an 8-week period a low riboflavin diet(5ug riboflavin/day) or a control diet(30ug/day) supplied either ad libitum or by pair feeding in order to study the effect of riboflavin on the metabolism of lipids and neurotransmitters. Erythrocyte glutathione reductase (EGR) and monomine oxidase(MAO) activity in the liver and brain were assayed. EGR activity coefficient in riboflavin deficient rats was significantly higher than in ad libitum controls whereas MAO activity was decreased in the deficient rats. Fatty acid composition showed a different trend in the serum, liver and brain. In the serum, the concentrations of essential fatty acids and $\omega$-3 fatty acids(eicosapentaenoic acid, docosahexaenoic acid)were decreased about 20-40% in the deficient and pair-fed than in the ad libitum controls. Brain serotonin and 5-HIAA(5-hydroxyindole acetic acid) concentrations were decreased in the riboflavin deficient rats. Learning ability measured by a water maze and exploratory activity using the open field test were not impaired in the deficient rats. These results indicate that brain lipid metabolism was protected in subclinical riboflavin deficiency, however, riboflavin deficiency affected brain serotonin content.

• Korean Journal of Environmental Biology
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• v.28 no.2
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• pp.79-85
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• 2010

To examine the effect of Codium fragile on blood cholesterol and lipid metabolism, hyperlipidemia was induced in experimental animal rats through the administration of a hypercholesterolemic diet. Codium fragile powder was then administered to the rats for 5 weeks, after which, blood biochemical changes such as blood cholesterol, Aspartate Aminotransferase (AST: serum SGOT) and Alanine Aminotransferase (ALT: serum SGPT) enzyme activity, etc. were determined. And histological changes in liver cells were examined using an electron microscope. Codium fragile treatment resulted in a significant reduction of the levels of total cholesterol, blood triglyceride and low-density cholesterol (LDL. Chol) compared to the control rats. In contrast the expression levels of high-density cholesterol (HDL. chol.) were increased. The AST value of the Codium fragile administration group was significantly reduced and the blood ALT value of the Codium fragile group showed a significant decrease in comparison to the negative control group. In summary, this study demonstrated the beneficial possibilities of Codium fragile in improving the abnormality of lipid metabolism caused by liver cell damage and hyperlipidemia.