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标题：Measurement of parameters of cholic acid kinetics in plasma using a microscale stable isotope dilution technique: application to rodents and humans
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作者：Christian V. Hulzebos ; Lorraine Renfurm ; Robert H. Bandsma 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2001
卷号：42
期号：11
页码：1923-1929
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：A stable isotope dilution method is described that allows measurement of cholic acid (CA) kinetics, that is, pool size, fractional turnover rate (FTR), and synthesis rate in mice, rats, and humans. Decay of administered [2,2,4,4-²H₄]CA enrichment was measured in time in 50-μl plasma samples by gas-liquid chromatography/electron capture negative chemical ionization-mass spectrometry, applying the pentafluorobenzyl-trimethylsilyl derivative. The kinetic data expressed species-dependent differences. The CA pool sizes were 16.8 ± 2.1, 10.6 ± 1.2, and 2.4 ± 0.7 μmol/100 g body weight for mice, rats, and humans, respectively. The FTR values were 0.44 ± 0.03, 0.88 ± 0.10, and 0.46 ± 0.14 per day for mice, rats, and humans. The corresponding synthesis rates were 7.3 ± 1.6, 9.3 ± 0.1, and 1.0 ± 0.2 μmol/100 g body weight per day. The human data agreed well with literature data obtained by conventional isotope dilution techniques. For rats and mice these are the first reported isotope dilution data. The method was validated by confirmation of isotopic equilibrium between biliary CA and plasma CA in the rat. Its applicability was demonstrated by the observation of increased CA FTR and CA synthesis rate in rats fed cholestyramine, which is known to increase fecal bile acid excretion. The presented stable isotope dilution method enables the determination of CA kinetic parameters in small plasma samples. The method can be applied in unanesthetized rodents with an intact enterohepatic circulation and may also be valuable when studying the development of human neonatal bile acid kinetics. —Hulzebos, C. V., L. Renfurm, R. H. Bandsma, H. J. Verkade, T. Boer, R. Boverhof, H. Tanaka, I. Mierau, P. J. J. Sauer, F. Kuipers, and F. Stellaard. Measurement of parameters of cholic acid kinetics in plasma using a microscale stable isotope dilution technique: application to rodents and humans. J. Lipid Res. 2001. 42: 1923–1929.
关键词：bile acid metabolism ; fractional turnover rate ; mass spectrometry ; pool size ; synthesis