Premium
Results of L‐[1‐ 13 C]phenylalanine breath test with air isotope ratio mass spectrometry can reflect the activity of phenylalanine hydroxylase in cirrhotic rat liver
Author(s) -
Yan Weili,
Xiong Ping,
Liu Zhengwei,
Huang Gang
Publication year - 2006
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2345
Subject(s) - chemistry , phenylalanine , excretion , breath test , medicine , hepatocyte , isotope , endocrinology , isotope ratio mass spectrometry , liver function , phenylalanine hydroxylase , mass spectrometry , chromatography , biochemistry , amino acid , in vitro , physics , quantum mechanics , helicobacter pylori
The L‐[1‐ 13 C]phenylalanine breath test (PheBT) could potentially advance the evaluation of hepatocyte function and liver functional reserve. However, because the factors influencing PheBT results have not been clarified, the clinical application of the test has been limited. This study investigated the relationship between the parameters of PheBT, performed with air isotope ratio mass spectrometry, and the activity of phenylalanine hydroxylase (PAH), the phenylalanine metabolism rate‐limiting enzyme, in rat liver, and proposes valid parameters for the assessment of liver function. Chronic injury to the liver was induced by the administration of CCl 4 to male Sprague‐Dawley rats for either 8 or 12 weeks. Livers from rats in the two cirrhotic groups were discolored, enlarged and roughly textured, with cells filled with fat granules of various sizes, pseudolobuli formations, and regenerated tubercles. Of the 12 parameters tested, only the unit liver weight (LW) breath test parameters, including the maximum abundance of 13 C in breath ( 13 C max /LW), 13 C abundance in breaths 2 and 7 min after administration of L‐[1‐ 13 C]phenylalanine ( 13 C‐phe) ( 13 C 2 /LW and 13 C 7 /LW), cumulative 13 C excretion 10 and 30 min after 13 C‐phe administration (AUC 10 /LW and AUC 30 /LW), and the 13 C excretion rate constant (PheBT‐k/LW) were significantly affected in the chronic liver injury groups. There was no significant difference in the total PAH activity in liver among the three groups, but there was significant difference in unit LW PAH activity. Total PAH activity in the liver was significantly correlated with 13 C max , 13 C 2 , 13 C 7 , AUC 10 , AUC 30 and PheBT‐k, while the unit LW PAH activity was significantly correlated with 13 C max /LW, 13 C 2 /LW, 13 C 7 /LW, AUC 10 /LW, AUC 30 /LW and PheBT‐k/LW. PheBT‐k/LW was also correlated with biochemical indices that are used to assess liver function. The present findings indicate that the PheBT results based on air isotope ratio mass spectrometry can quantitatively reflect the change in total PAH activity in the livers of chronically injured rats. PheBT‐k and PheBT‐k/LW are the most sensitive among the test parameters, and can be used to assess liver functional reserve and hepatocyte damage at the molecular level. Copyright © 2006 John Wiley & Sons, Ltd.