Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation
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...
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00938/full |
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| author | Elisabetta Teopompi Patrizia Risé Roberta Pisi Carola Buccellati Marina Aiello Giovanna Pisi Candida Tripodi Valentina Fainardi Enrico Clini Enrico Clini Alfredo Chetta G. Enrico Rovati Angelo Sala Angelo Sala |
| author_facet | Elisabetta Teopompi Patrizia Risé Roberta Pisi Carola Buccellati Marina Aiello Giovanna Pisi Candida Tripodi Valentina Fainardi Enrico Clini Enrico Clini Alfredo Chetta G. Enrico Rovati Angelo Sala Angelo Sala |
| author_sort | Elisabetta Teopompi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T03:57:49Z |
| format | Article |
| id | doaj.art-5ab6ddeea45741f3889b04130c888cfe |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T03:57:49Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-5ab6ddeea45741f3889b04130c888cfe2022-12-22T02:03:03ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-08-011010.3389/fphar.2019.00938471437Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid SupplementationElisabetta Teopompi0Patrizia Risé1Roberta Pisi2Carola Buccellati3Marina Aiello4Giovanna Pisi5Candida Tripodi6Valentina Fainardi7Enrico Clini8Enrico Clini9Alfredo Chetta10G. Enrico Rovati11Angelo Sala12Angelo Sala13Respiratory Disease Unit, Department of Medicine and Surgery, University Hospital, Parma, Parma, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milano, ItalyRespiratory Disease Unit, Department of Medicine and Surgery, University Hospital, Parma, Parma, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milano, ItalyRespiratory Disease Unit, Department of Medicine and Surgery, University Hospital, Parma, Parma, ItalyDepartment of Pediatrics, CF Unit Children Hospital, University Hospital of Parma, Parma, ItalyDepartment of Pediatrics, CF Unit Children Hospital, University Hospital of Parma, Parma, ItalyDepartment of Pediatrics, CF Unit Children Hospital, University Hospital of Parma, Parma, ItalyDepartment of Medical and Surgical Sciences, University of Modena Reggio Emilia, Modena, ItalyDepartment of Medical and Surgical Sciences SMECHIMAI, University Hospital of Modena, Modena, ItalyRespiratory Disease Unit, Department of Medicine and Surgery, University Hospital, Parma, Parma, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milano, ItalyDepartment of Pharmacological and Biomolecular Sciences, University of Milan, Milano, ItalyIBIM, Consiglio Nazionale delle Ricerche, Palermo, ItalyCystic 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.https://www.frontiersin.org/article/10.3389/fphar.2019.00938/full15-lipoxygenasesputuminflammatory mediatorsdocosahexaenoic acid-DHAarachidonic acid (AA or eicosatetraenoic acid) |
| spellingShingle | Elisabetta Teopompi Patrizia Risé Roberta Pisi Carola Buccellati Marina Aiello Giovanna Pisi Candida Tripodi Valentina Fainardi Enrico Clini Enrico Clini Alfredo Chetta G. Enrico Rovati Angelo Sala Angelo Sala Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation Frontiers in Pharmacology 15-lipoxygenase sputum inflammatory mediators docosahexaenoic acid-DHA arachidonic acid (AA or eicosatetraenoic acid) |
| title | Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation |
| title_full | Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation |
| title_fullStr | Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation |
| title_full_unstemmed | Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation |
| title_short | Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation |
| title_sort | arachidonic acid and docosahexaenoic acid metabolites in the airways of adults with cystic fibrosis effect of docosahexaenoic acid supplementation |
| topic | 15-lipoxygenase sputum inflammatory mediators docosahexaenoic acid-DHA arachidonic acid (AA or eicosatetraenoic acid) |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00938/full |
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