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

Cipollina, C and Salvatore, SR and Muldoon, MF and Freeman, BA and Schopfer, FJ (2014) Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives. PLoS ONE, 9 (4).

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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. Methods: 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. Results: 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. Conclusions: The endogenous detection of these electro.©2014 Cipollina et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Cipollina, Cchc117@pitt.eduCHC117
Salvatore, SRsrs107@pitt.eduSRS107
Muldoon, MFmfm10@pitt.eduMFM10
Freeman, BAfreerad@pitt.eduFREERAD
Schopfer, FJfjschopfer@katz.pitt.eduFJS2
ContributionContributors NameEmailPitt UsernameORCID
Date: 15 April 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0094836
Schools and Programs: School of Medicine > Medicine
School of Medicine > Pharmacology and Chemical Biology
Refereed: Yes
Date Deposited: 23 Jun 2014 20:55
Last Modified: 01 Mar 2019 15:57


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