Measurement and diagnostic use of hepatic cytochrome P450 metabolism of oleic acid in liver disease

作者：Thum Thomas^*; Batkai Sandor; Malinski Philipp G; Becker Thomas; Mevius Iris; Klempnauer Juergen; Meyer Hartmut H; Froelich Juergen C; Borlak Juergen; Tsikas Dimitrios

来源：Liver International, 2010, 30(8): 1181-1188.

DOI：10.1111/j.1478-3231.2010.02310.x

• chronic liver disease
• cirrhosis
• CYP2C8
• 2C9
• 1A2
• 2C19
• 3A4
• 3A7
• cytochrome P450
• epoxidation
• hepatitis C
• gas chromatography-tandem mass spectrometry
• oleic acid

Background
Oleic acid is a major systemically circulating fatty acid in humans with atheroprotective and immunomodulatory properties. As of today, the contribution of individual cytochrome P450 (CYP) mono-oxygenases to the epoxidation of this fatty acid is unknown. Furthermore, the extent of the oleic acid oxidation product cis-9,10-epoxyoctadecanoic acid (cis-EODA) in humans and its plasma levels in patients with impaired liver function are not known.
Patients and methods
We studied cis-EODA in plasma of patients suffering from chronic liver diseases, a condition that often displays impaired liver CYP enzyme activities. Fifteen CYP mono-oxygenases were investigated in vitro as a potential source of cis-EODA.
Results
Strikingly, plasma levels of cis-EODA were significantly repressed (P < 0.0005) when patients with liver impairment (n=16) were compared with healthy subjects (n=14). Production of cis-EODA was catalysed by CYP in the following order: 2C8, 2C9, 2C19, 3A4, 1A2 and CYP3A7.
Conclusion
cis-EODA plasma concentrations are decreased in hepatic disease with impaired liver function. Oleic acid is primarily oxidized to oleic acid oxide (cis-EODA) by CYP2C and CYP3A mono-oxygenases. The liver is the major organ responsible for the oxidation of oleic acid to cis-EODA, and thus, cis-EODA may be a suitable biomarker to assess liver function.

• 出版日期2010-9