• Journal of Animal Science and Technology
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• v.55 no.2
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• pp.147-153
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• 2013

Lipid metabolism in mature male mice may be different from immature male mice, but the relationship of lipid metabolism, especially n-6 fatty acid metabolism, and sexual maturation is not clearly established. This study was carried out to elucidate whether sexual maturation may affect the metabolism of functional n-6 fatty acids of lipid components by investigating the composition of fatty acids in the longissimus muscle tissues of mature and immature male mice with GC and analyzing the expression of genes and proteins for synthesis of n-6 fatty acids with real-time PCR and western blotting, respectively. Mature male mice showed significantly higher testosterone level in the sera. Similarly, n-6 fatty acids, levels of linoleic acid (LA 18:2n-6) and total n-6 PUFA (Polyunsaturated fatty acids) were increased, but the levels of ${\gamma}$-linolenic acid (GLA; 18:3n-6), dihomo-${\gamma}$-linolenic acid (DGLA; 20:3n-6) and arachidonic acid (AA; 20:4 n-6) were decreased in the mature male mice. mRNA levels of ${\Delta}5$-desaturase (FASD1) and elongase (ELOVL5) genes related to n-6 fatty acid metabolism increased. However, the level of FADS1 protein only increased in mature male mice. In conclusion, this study suggested that sexual maturation of male mice affected n-6 fatty acid metabolism by stimulating the expression of enzyme FADS1 of n-6 PUFA metabolism.

• 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.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.664-668
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• 2002

KR-31543,(2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran is a new neuroprotetive agent for ischemia-reperfusion damage. The in vitro and in vivo metabolism of KR-31543 in rats has been studied by LC-electrospray mass spectrometry. Rat liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of a metabolite M1. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC-MS/MS analysis with the synthesized authentic standard. Rat CYP3A1 and 3A2 are the major CYP isozymes involved in the formation of M1.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.239-245
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• 2004

KR-31543, (2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2 -methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran, is a new neuroprotective agent for preventing ischemia-reperfusion damage. This study was performed to identify the metabolic pathway of KR-31543 in human liver microsomes and to characterize cytochrome P450 (CYP) enzymes that are involved in the metabolism of KR-31543. Human liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of two metabolites, M1 and M2. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC/MS/MS analysis with a synthesized authentic standard, and M2 was suggested to be hydroxy-KR-31543. Correlation analysis between the known CYP enzyme activities and the rates of the formation of M 1 and M2 in the 12 human liver microsomes have showed significant correlations with testosterone 6$\beta$-hydroxylase activity (a marker of CYP3A4). Ketoconazole, a selective inhibitor of CYP3A4, and anti-CYP3A4 monoclonal antibodies potently inhibited both N-hydrolysis and hydroxylation of KR-31543 in human liver microsomes. These results provide evidence that CYP3A4 is the major isozyme responsible for the metabolism of KR-31543 to M1 and M2.

• Journal of the Korean Applied Science and Technology
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• v.31 no.3
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• pp.509-516
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• 2014

This study was done to investigate the carbohydrate metabolism related enzyme activities and antioxidative effects of Nelumbo nucifera(N.N) Root in streptozotocin (STZ)-induced diabetic rats. The contents of serum glucose, triglyceride (TG) and Total cholesterol were significantly decreaed in N.n treated group compared to the those of STZ-control group. The activity of glucose-6-pase(G-6-Pase) was significantly decreased in N.N treated group. Also the activity of glucokinase(Gk) was significantly increaed in N.N treated group. The content of hepatic glycogen was significantly increaed in N.N treated group, in addition, content of malondialdehyde(MDA) was significanly decreased in N.N treated group. Also, content of glutathione(GSH) was significanly increased in N.N treated froup. whereas, activity of catalase(CAT) was significantly decreaed in N.N treated group compared to the those of STZ-control group. activity of glutathione peroxidase(GSH-Px) was inecreaed. In conclusion, these results indicated that ethanol extract of N.N would have carbohydrate metabolism antioxidative effects in STZ-induced diabetic rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.1
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• pp.121-126
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• 1995

The purpose of this study was to investigate the effects of Natto supplementation on lipid metabolism in rats. Male rats were fed on casein(CON group), steamed soybean(SS group), conventional Natto(N-1 group), garlic(2%) added Natto(N-2 group), red pepper oleoresin(0.2%) added Natto(N-3 group) and galic(2%) and red pepper oleoresin(0.2%) added Natto(N-4 group) as a protein source for 4 weeks. Serum and liver cholesterol levels were significantly lower in the experimental groups than in the control group. Especially, dietary N-2, N-3 and N-4, compared with CON, reduced markedly the concentration of serum cholesterol. The concentration of serum HDL-cholesterol was higher markedly in the N-4 group than in the control group. The concentration of serum triglyceride was significantly lower in the N-1, N-2, N-3 and N-4 groups than in the control group. Garlic and red pepper added Natto fed groups(N-2, N-3, N-4) showed more excreion of fecal bile acid when compared with those values of casein fed group. The results indicate that spice added Natto supplementation may have more beneficial roles in lipid metabolism through reduced cholesterol levels and increased fecal bile acid excretion.

• Asian-Australasian Journal of Animal Sciences
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• v.5 no.4
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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.

• Applied Biological Chemistry
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• v.50 no.3
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• pp.233-237
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• 2007

The roots of Brassica campestris ssp rapa were extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and $H_{2}O$. From the EtOAc and n-BuOH fractions, five compounds were isolated through the repeated silica gel column chromatographies. From the result of spectroscopic data including NMR and MS, the chemical structures of the compounds were determined as palmitic acid methyl ester (1), linolenic acid methyl ester (2), linoleic acid methyl ester (3), ${\beta}-sitosterol$ (4) and daucosterol (5).

• Biomolecules & Therapeutics
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• v.4 no.3
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• pp.251-256
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• 1996

The metabolism of carbinoxamine, 2-[(4-chlorophenyl)-2-pyridinyl-methoxy]-N, N-dimethylethaneamine, was studied in adult male volunteers after an oral dose of 15 mg. Solvent extracts of urine obtained with or without enzyme hydrolysis were analyzed by gas chromatography-mass spectrometry after derivatization with MSTFA/TMSCl (N-methyl-N-trimethylsilyltrifluoroacetamide/trimethyl chlorosilane). The structures of metabolites were determined based on the electron impact (EI) and chemical ionization (CI) mass spectra. Nonconjugated metabolites identified in the urine were carbinoxamine, nor-carbinoxamine, and bits-nor-carbinoxamine. Parent drug, nor-carbinoxamine, and bits-nor-carbinoxamine were also detected as conjugated forms. These metabolites observed in human urine were different from those previously reported in the rat. Urinary excretions of carbinoxamine were reached to maxima in 4 hours after drug administration with 4.9%-8.1% and 2.5-4.2% of the dose excreted during 24 h as carbinoxamine and its glucuronide, respectively.

• Journal of Nutrition and Health
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• v.31 no.1
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• pp.5-12
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• 1998

This study was designed to examine how dietary protein levels affect organ growth and protein metabolism in early and normally weaned rats. Early and normally weaned rats separated fro the dam on the 15th and 121st day postpartum, respectively. were fed diets containing three levels of protein : low(10%) , normal (20%),and high(40%) . On the 35th day, the weight and DNA, RNA and protein contents in brain , liver, and kidney were determined to ascertain organ and cellular growth. Furthermore, serum total protein , albumin , $\alpha$-amino N and creatine and urinary urea N, and creatinine were determined in order to ascertain protein metabolism and renal functions. Dietary protein levels were not observed to significantly affect total DNA content, which may represent an index of cell number in the liver, brain and kidney. Fresh weight and protein/DNA ratio, which may represent indices of cell size, significantly increased in proportion to dietary protein in the kidney. As for the early weaned rats , the liver cell size significantly decreased. Dietary protein levels and weaning periods did not affect serum total protein and albumin . However, serum urea-N significantly increased in proportion to dietary protein levels whereas serum $\alpha$-amino N was decreased by early weaning . Nitrogen retention was lower in early weaned rats fed low or high levels of protein than in normally weaned rats. The results demonstrate that low or high levels of dietary protein have less desirable effects on protein metabolism in prematurely weaned rats.