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Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation
- Source :
- Frontiers in Pharmacology, Vol 10 (2019), Frontiers in Pharmacology
- Publication Year :
- 2019
- Publisher :
- Frontiers Media SA, 2019.
-
Abstract
- Cystic fibrosis (CF) is an autosomal recessive disorder, caused by genetic mutations in CF transmembrane conductance regulator protein. Several reports have indicated the presence of specific fatty acid alterations in CF patients, most notably decreased levels of plasmatic and tissue docosahexaenoic acid (DHA), the precursor of specialized pro-resolving mediators. We hypothesized that DHA supplementation could restore the production of DHA-derived products and possibly contribute to a better control of the chronic pulmonary inflammation observed in CF subjects. Sputum samples from 15 CF and 10 chronic obstructive pulmonary disease (COPD) subjects were collected and analyzed by LC/MS/MS, and blood fatty acid were profiled by gas chromatography upon lipid extraction and transmethylation. Interestingly, CF subjects showed increased concentrations of leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and 15-hydroxyeicosatetraenoic acid (15-HETE), when compared with COPD patients, whereas the concentrations of DHA metabolites did not differ between the two groups. After DHA supplementation, not only DHA/arachidonic acid (AA) ratio and highly unsaturated fatty acid index were significantly increased in the subjects completing the study (p < 0.05) but also a reduction in LTB4 and 15-HETE was observed, together with a tendency for a decrease in PGE2, and an increase in 17-hydroxy-docosahexaenoic acid (17OH-DHA) levels. At the end of the washout period, LTB4, PGE2, 15-HETE, and 17OH-DHA showed a trend to return to baseline values. In addition, 15-HETE/17OH-DHA ratio in the same sample significantly decreased after DHA supplementation (p < 0.01) when compared with baseline. In conclusion, our results show here that in CF patients, an impairment in fatty acid metabolism, characterized by increased AA-derived metabolites and decreased DHA-derived metabolites, could be partially corrected by DHA supplementation.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Leukotriene B4
inflammatory mediators
Cystic fibrosis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
15-lipoxygenase
Internal medicine
medicine
Pharmacology (medical)
Unsaturated fatty acid
Original Research
Pharmacology
chemistry.chemical_classification
arachidonic acid (AA or eicosatetraenoic acid)
Fatty acid metabolism
lcsh:RM1-950
sputum
Fatty acid
15-lipoxygenase, sputum, inflammatory mediators
docosahexaenoic acid-DHA
medicine.disease
lcsh:Therapeutics. Pharmacology
030104 developmental biology
Endocrinology
chemistry
Docosahexaenoic acid
030220 oncology & carcinogenesis
lipids (amino acids, peptides, and proteins)
Arachidonic acid
Transmethylation
Subjects
Details
- ISSN :
- 16639812
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pharmacology
- Accession number :
- edsair.doi.dedup.....b3768d6bc90eca0402fab5728367dc0a