Abstract
Cysteinyl leukotrienes (LTs) are potent lipid mediators which are predominantly eliminated via bile. Their metabolic inactivation and degradation proceeds by β-oxidation. However, although bile is the optimal material for analysis of LTs in man, only very sparse data on bile LT concentration under normal or pathophysiological conditions exist. The aim of the present study was to present for the first time a complete profile of endogenous LTs in human bile and to investigate the importance of bile LT analysis in peroxisomal and mitochondrial β-oxidation deficiency. Cysteinyl LTs and their oxidation metabolites were analysed after HPLC separation by specific immunoassays or gas chromatography-mass spectrometry. Under physiological conditions, LTs are found in human bile ( n=8) in the nanomolar range with LTD 4 predominating, whereas the other LTs were present in similar amounts. In bile of a patient with a peroxisome biogenesis disorder (Zellweger syndrome, ZS) LTE 4 was found to be slightly increased, whereas both ω-oxidation metabolites of LTE 4, ω-hydroxy-LTE 4 and ω-carboxy-LTE 4, were highly increased (about 12–18 times). The β-oxidation metabolite ω-carboxy-tetranor-LTE 3 was below the detection limit (<0.1 nmol/l; controls 1.4±1.2 nmol/l). This abnormal profile demonstrates an impaired degradation of LTs in ZS. In contrast, patients with X-linked adrenoleukodystrophy (X-ALD), medium-chain acyl CoA dehydrogenase deficiency (MCAD) as well as very long-chain acyl CoA dehydrogenase deficiency (VLCAD) did not show any differences in their biliary profile of LTs compared to controls. Increased levels of the biologically active cysteinyl LTs in the bile of patients with ZS might be of pathophysiological significance in the course of the disease, e.g. contributing to liver injury. In addition, our data confirm that the β-oxidation of cysteinyl LTs in vivo occurs in peroxisomes and not in mitochondria.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
