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Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives

Cipollina, Chiara ; Salvatore, Sonia R ; Muldoon, Matthew F ; Freeman, Bruce A ; Schopfer, Francisco J Norata, Giuseppe Danilo

PloS one, 2014-04, Vol.9 (4), p.e94836 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives
Autor: Cipollina, Chiara ; Salvatore, Sonia R ; Muldoon, Matthew F ; Freeman, Bruce A ; Schopfer, Francisco J
Norata, Giuseppe Danilo
Assuntos: Acetic acid ; Active control ; Adult ; Adults ; Anti-Inflammatory Agents - chemistry ; Anti-Inflammatory Agents - metabolism ; Anti-Inflammatory Agents - pharmacology ; Arachidonate 5-Lipoxygenase - metabolism ; Arachidonic acid ; Biology ; Biology and Life Sciences ; Calcium ; Cardiovascular diseases ; Clinical trials ; Cyclooxygenase-2 ; Derivatives ; Diet ; Diet therapy ; Dietary supplements ; Docosahexaenoic acid ; Dose-Response Relationship, Drug ; Drug dosages ; Fatty acids ; Fatty Acids, Omega-3 - biosynthesis ; Fatty Acids, Omega-3 - chemistry ; Fatty Acids, Omega-3 - pharmacology ; Female ; Fish oils ; Gene expression ; Health aspects ; Health risks ; Human subjects ; Humans ; Inflammation ; Ketones ; Ketones - chemistry ; Leukocytes (neutrophilic) ; Lipids ; Macrophages ; Male ; Mass spectrometry ; Mass spectroscopy ; Medicine ; Medicine and Health Sciences ; Metabolites ; Middle Aged ; Modulation ; Neutrophils ; Neutrophils - drug effects ; Neutrophils - metabolism ; NF-κB protein ; NRF2 protein ; Oils & fats ; Omega-3 fatty acids ; Pharmacology ; Phorbol 12-myristate 13-acetate ; Polyunsaturated fatty acids ; Proteins ; Research and Analysis Methods ; Risk factors ; Signaling ; Soybean oil ; Supplementation ; Technicians
É parte de: PloS one, 2014-04, Vol.9 (4), p.e94836
Notas: Conceived and designed the experiments: CC SRS MFM BAF FJS. Performed the experiments: CC SRS. Analyzed the data: CC SRS BAF FJS. Contributed reagents/materials/analysis tools: CC SRS MFM BAF FJS. Wrote the paper: CC BAF FJS.
Competing Interests: The authors have read the journal's policy and have the following conflicts to declare: Bruce A. Freeman and Francisco J. Schopfer acknowledge financial interest in Complexa, Inc; Bruce A. Freeman acknowledges financial interest in Nitromega Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Current address: Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy
Descrição: Dietary ω-3 polyunsaturated fatty acids (PUFAs) decrease cardiovascular risk via suppression of inflammation. The generation of electrophilic α,β-unsaturated ketone derivatives of the ω-3 PUFAs docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in activated human macrophages is catalyzed by cyclooxygenase-2 (Cox-2). These derivatives are potent pleiotropic anti-inflammatory signaling mediators that act via mechanisms including the activation of Nrf2-dependent phase 2 gene expression and suppression of pro-inflammatory NF-κB-driven gene expression. Herein, the endogenous generation of ω-3 PUFAs electrophilic ketone derivatives and their hydroxy precursors was evaluated in human neutrophils. In addition, their dietary modulation was assessed through a randomized clinical trial. Endogenous generation of electrophilic omega-3 PUFAs and their hydroxy precursors was evaluated by mass spectrometry in neutrophils isolated from healthy subjects, both at baseline and upon stimulation with calcium ionophore. For the clinical trial, participants were healthy adults 30-55 years of age with a reported EPA+DHA consumption of ≤300 mg/day randomly assigned to parallel groups receiving daily oil capsule supplements for a period of 4 months containing either 1.4 g of EPA+DHA (active condition, n = 24) or identical appearing soybean oil (control condition, n = 21). Participants and laboratory technicians remained blinded to treatment assignments. 5-lypoxygenase-dependent endogenous generation of 7-oxo-DHA, 7-oxo-DPA and 5-oxo-EPA and their hydroxy precursors is reported in human neutrophils stimulated with calcium ionophore and phorbol 12-myristate 13-acetate (PMA). Dietary EPA+DHA supplementation significantly increased the formation of 7-oxo-DHA and 5-oxo-EPA, with no significant modulation of arachidonic acid (AA) metabolite levels. The endogenous detection of these electrophilic ω-3 fatty acid ketone derivatives supports the precept that the benefit of ω-3 PUFA-rich diets can be attributed to the generation of electrophilic oxygenated metabolites that transduce anti-inflammatory actions rather than the suppression of pro-inflammatory AA metabolites. ClinicalTrials.gov NCT00663871.
Editor: United States: Public Library of Science
Idioma: Inglês

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Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives

Cipollina, Chiara ; Salvatore, Sonia R ; Muldoon, Matthew F ; Freeman, Bruce A ; Schopfer, Francisco J Norata, Giuseppe Danilo

United States: Public Library of Science

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