OBJECTIVE: Pro-resolving mediators (SPM) are the oxidative products of omega-3 fatty acids which help maintain and control the balance of inflammation and its resolution in the body. Extensive research has shown SPMs can act both chronically and acutely to decrease excessive inflammation and protect against excessive inflammation in cardiovascular disease (atherosclerosis, myocardial infarction, and heart failure). Their powerful effects to resolve inflammation suggest that they will be natural therapeutics for Coronavirus infections and ischemic brain injuries. To optimize mixtures and doses for the fastest and most effective acute delivery of the water-insoluble acylglycerol omega-3 fatty acid (DHA and EPA), we studied fluidity and structural organization in phospholipid membranes by 13C NMR Spectroscopy.
METHODS: As models for delivery to cells, acylglycerol omega-3 fatty acids were mixed in increasing proportions with phospholipids and sonicated to make small unilamellar vesicles (SUV) for NMR Spectroscopy.
RESULTS: Spectral analysis showed that low proportions (< 5-10 mol %) of omega-3 diglycerides incorporated into the bilayer structure of the phospholipid vesicles without disruption of the bilayer or phase separation. With increases (up to 40mol%) the spectra exhibited separation of the carbonyl peaks and line broadening. With omega-3 triglycerides the narrow aliphatic, glycerol, and carbonyl regions did not exhibit line broadening and were very similar for both omega-3 fatty (DHA or EPA). The olefinic region has the distinct peaks that differentiates one omega-3 fatty acid from the other. Triglyceride mole percentages less than 20mol% that are incorporated into PC emulsions with omega-3 fatty acids do not give detectable signals but at 40mol% we see line broadening of the PC carbonyls.
CONCLUSION: At low concentrations of diglycerides with omega-3 fatty acids the vesicle carbonyls were essentially unaffected but at relatively high concentrations they incorporated into the phospholipid vesicles and changed the structural organization at the aqueous interface. In triglycerides with omega-3 fatty acids there was a complete assignment of numerous olefinic peaks, which remained very narrow at all proportions. Comparison of EPA and DHA distinguished the two FA, which will make it possible to quantify whether EPA enters cells more readily, as has been argued because they appear to have better cardiovascular therapeutic effects than DHA in some clinical studies. Acute delivery is feasible with SUVs, but future studies should focus on emulsions with a large triglycerides omega-3 fatty acid core with a greater abundance of triglycerides relative to phospholipid to deliver much larger doses of DHA and EPA.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/45563 |
| Date | 01 February 2023 |
| Creators | Gubler, Troy W. |
| Contributors | Hamilton, James A., Deeney, Jude T. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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