• Archives of Pharmacal Research
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• 제26권1호
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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.

• 환경생물
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• 제27권3호
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• pp.279-284
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• 2009

In order to understand food sources-metabolism for the pacific oyster (Crassostrea gigas), the stable isotope ratios of carbon (${\delta}^{13}C$) and nitrogen (${\delta}^{15}N$) of its gut, gill, and muscle as well as potential food sources (particulate organic matter, sedimentary organic matter, benthic microalgae, seagrass detritus) were determined in Dongdae Bay. Average ${\delta}^{13}C$ and ${\delta}^{15}N$ values reflect that oysters primarily fed on sedimentary organic matter as opposed to suspended organic matter during summer and winter seasons. However, the relatively enriched $^{15}N$ values of particulate organic matter (>$250{\mu}m$) and sedimentary organic matter in the summer may be due to the photosynthetic incorporation of $^{15}N$-enriched nitrogen (DIN) or the spawning events of bivalves. Specific oyster tissues (gut, gill, and muscle) revealed different metabolic pathways, which were determined through analysis of ${\delta}^{13}C$ and ${\delta}^{15}N$ in each organ. The present results suggest the determination of carbon and nitrogen stable isotopes to be a useful approach in ecological research related to the food sources- metabolism of Crassostrea gigas.

• Asian-Australasian Journal of Animal Sciences
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• 제26권12호
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• pp.1726-1731
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• 2013

The effects of different dietary electrolyte balance (DEB) on growth performance, nitrogen (N) metabolism and some blood biochemical parameters were investigated in 2 to 3 months old growing rabbits. A total of 150 growing rabbits of 2 months age were randomly divided into five groups according to average body weight, with 30 rabbits in each group. The DEB levels of the five experimental diets were -154, -3.16, +201, +347, and +500 meq/kg of dry matter (DM), respectively. There was a 7-d adaptation period and a 23-d experimental period. The results showed that the DEB levels had a quadratic affect on the average daily feed intake (ADFI) (p<0.001). The greatest ADFI was achieved when the DEB level was +201 meq/kg DM. Fecal N (FN) content linearly decreased (0.047), while digestible N (DN), retained N (RN), efficiency of intake N converted into digestible N (DN/IN) and the efficiency of intake N converted into retained N (RN/IN) linearly increased with the DEB increase (0.020, 0.004, 0.021, and 0.049, respectively). Serum phosphorus (P) ion content linearly increased with the DEB increase (p = 0.036). The DEB had a quadratic relationship with serum anion gap (AG) (p = 0.002) and serum parathyroid hormone (PTH) content (p = 0.016). The DEB levels quadratically affected base excess (BE) in the plasma (p<0.001). In conclusion, the DEB unaffected growth performance but affected feed intake, N metabolism and some blood biochemical parameters of growing rabbits.

• Asian-Australasian Journal of Animal Sciences
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• 제25권9호
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• pp.1229-1236
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• 2012

Our previous studies showed that kisspeptin-10 (Kp-10) injected in vivo can markedly increase lipid anabolism in liver of quails. In order to investigate the direct effect of Kp-10 on lipid metabolism of hepatocytes in birds, cells were separated from embryos livers and cultured in vitro with 0, 100 and 1,000 nM Kp-10, respectively. The results showed that after 24 h treatment, cells viability was not affected by 100 nM Kp-10, but showed a mild decrease with 1,000 nM Kp-10 compared to the control cells. Based on the results of the cell viability, 100 nM dosage of Kp-10 was selected for the further study and analysis. Compared with control cells, total cholesterol (Tch) contents in 100 nM treated cells were increased by 51.23%, but did not reach statistical significance, while the level of triglyceride (TG), high density of lipoprotein-cholesterol (HDL-C) and low density of lipoprotein-cholesterol (LDL-C) were significantly increased. Real-time PCR results showed that ApoVLDL-II mRNA expression had a tendency to increase, genes including sterol regulatory element-binding protein-1 (SREBP-1), acetyl coenzyme A carboxylase ${\alpha}$ ($ACC{\alpha}$), carnitine palmitoyltransferase 1 (CPT1), 3-hydroxyl-3-methylglutaryl-coenzyme A reductases (HMGCR) and stearyl coenzyme A dehydrogenase-1 (SCD1) mRNA in hepatocytes were significantly down-regulated by 100 nM Kp-10. However, contrary to its gene expression, SREBP-1 protein expression was significantly up-regulated by 100 nM Kp-10. Some of the significant correlations in mRNA expression were found between genes encoding hepatic factors or enzymes involved in lipid metabolism in liver of birds. These results indicate that Kp-10 stimulates lipid synthesis directly in primary cultured hepatocytes of chickens.

• Asian-Australasian Journal of Animal Sciences
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• 제14권9호
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• pp.1221-1227
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• 2001

Young lambs (Suffolk wethers, n=18), which were 22 to 26 kg average BW, were chronically exposed to temperatures of +1 to +$4^{\circ}C$ (cold) or +21 to +$24^{\circ}C$ (warm) during 10 wk experimental periods. The sheep were closely shorn and were housed in individual metabolism crates in controlled environment rooms. Sheep consumed pelleted diets ad libitum, which consisted of mainly barley grain and brome grass, and contained 7, 11, or 14% CP. The experimental design consisted of a $2{\times}3$ factorial with a single crossover of environment treatment. Feed intake, BW, feces, and urine excretion were measured. Apparent digestibilities were not affected by diet CP concentration or temperature treatments; however, voluntary intake per kg BW was increased (p<0.05) by diet CP content in both environments. Growing lambs gained weight slightly faster in a cold environment when N intake was above 27 g/d. Nitrogen excretion and N balance were positively related (p<0.01) with diet CP content, and fecal N excretion was significantly increased (p<0.05) in the cold environment. Therefore, dietary CP content strongly influenced N metabolism; however, cold exposure did alter only fecal N excretion. The higher DM intake per kg BW at 11% CP diet in the cold environment permitted ADG comparable to 14% CP diet in the warm environment. The results of this study do support the hypothesis that lambs are better able to utilize a moderate reduction in the CP content of the diet in a cold environment.

• Asian-Australasian Journal of Animal Sciences
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• 제5권4호
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• pp.699-707
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• 1992

Three goats were fed with $^{15}N$-labelled rice straw to study the characteristics of digestion, assimilation, metabolism and excretion of C and N compounds from rice straw. It was shown that the amount of $^{15}N$ assimilated into the bodies of the two slaughtered goats accounted for 38.5 and 23.6% of the total amount of $^{15}N$ ingestion in the experimental diet by each goat. The $^{15}N$ excreted via the feces and urine for the three goats accounted for 34.8, 33.2 and 33.9% of the total amount of $^{15}N$ ingested in the feed of the 3 goats. The recoveries of $^{15}N$ from the two slaughtered goats were 73.3 and 57.5%, with the corresponding rates of $^{15}N$ loss 26.7 and 42.5% respectively. The amino acids digestibilities were 68.7 and 54.0%, while the digestibilities of carbohydrates were 74.8 and 67.7% respectively for goats 1 and 3.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.286.2-287
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• 2003

The purpose of this paper was to identify the metabolic pathway of a new neuroprotective agent, KR-31543 for ischemia-reperfusion damage in human liver microsomes and characterize cytochrome P450 (CYP) enzymes involved in the in vitro metabolism of KR-31543 generates two metabolites in human liver microsomes : M1, N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine and M2, hydroxy-KR-31543. (omitted)

• Archives of Pharmacal Research
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• 제17권6호
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• pp.428-433
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• 1994

The methabolism and phamacokinetics of a mixed disulfide S-(N, N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (AC-DDTC) were studied in rats. Two metabolites of AC-DDTC following iv and po administration were indentified in plasma and liver by HPLC and GC, namely N, N-diethyldithiocarbamate (DDTC) and the methyl ester of DDTC (Me-DDTC). AC-DDTC was very unstable in vivo and could not be detected neither in plasma nor in urine. Pharmacokinetic parameters of DDTC following intravenous administration of AC-DDTC (20 mg/kg) were calculated. DDTC has a low affinity to rat tissue and the body clearance was $9.0{\pm}3.4mkl/mim/kg$. The mean residence time (MRT) was $11.5{\pm}16.3 min$. After oral administration of 20 mg/kg AC-DDTC, maximal plasma concenttion ($C_{max}$) was $3.8{\pm}0.2 nmol/ml$ and the bioavailability was 7.04%. $C_{max}$ for DDTC at a dose of 120 mg/kg. AC-DDTC was $40.1{\pm}2.2 nmol/ml$. ART was $47.1{\pm}2.8min$.at a dose of 20 mg/kg and $110.5{\pm}6.0 min$ at 120 mg/kg.

• Asian-Australasian Journal of Animal Sciences
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• 제23권10호
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• pp.1333-1339
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• 2010

The present study was conducted to determine plasma acetate, glucose and protein metabolism using dilution of isotopes [[1-$^{13}C$]Na acetate, [U-$^{13}C$]glucose and [1-$^{13}C$]leucine (Leu)] in sheep fed rice straw (Oriza japonica L.). Four sheep were assigned to either rice straw (RS-diet) or mixed hay (MH-diet) with a crossover design. Nitrogen (N) intake and N digestibility were lower (p = 0.002 and p = 0.02, respectively) for RS-diet than MH-diet, but N retention did not differ (p>0.10) between the diets. Concentrations of rumen acetate tended to be lower (p = 0.07), and propionate was higher (p = 0.02) for RS-diet than MH-diet. Concentrations of plasma lactate, non-esterified fatty acids, Leu and ${\alpha}$-ketoisocaproic acid did not differ (p>0.10) between the diets, but plasma glucose and urea concentrations were lower (p = 0.01 and p = 0.003, respectively) for RS-diet than MH-diet. Turnover rate of plasma acetate did not differ (p = 0.39) between the diets, and plasma glucose and Leu turnover rates were numerically lower (p = 0.15 and p = 0.14, respectively) for RS-diet than MH-diet. Whole body protein synthesis and degradation did not differ (p>0.10) between the diets. Thus it can be concluded that the intermediary metabolism of acetate, glucose and protein on rice straw is comparable to mixed hay in sheep.

• Applied Biological Chemistry
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• 제50권3호
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• pp.233-237
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• 2007

순무 뿌리로부터 활성 물질을 분리 동정 하기 위하여 80% MeOH 수용액으로 추출하고 이를 여과, 감압 농축하여 MeOH 추출물을 얻었다. 이를 EtOAc분획, n-BuOH분획, $H_{2}O$분획으로 나누었으며, EtOAc분획과 n-BuOH분획에 대해 silica gel 및 ODS column chromatography를 실시하여 5종의 화합물을 분리 정제하였다. $^{1}H-NMR$, $^{13}C-NMR$, DEPT spectrum 및 Mass spectrum 등을 통하여 palmitic acid methyl ester(1), linolenic acid methyl ester(2), linoleic acid methyl ester(3), ${\beta}-sitosterol$(4), daucosterol(5)으로 구조를 결정하였다.