AN INVESTIGATION OF THE ANTI-INFLAMMATORY PROPERTIES OF METABOLITES OF EICOSAPENTAENOIC ACID
Open Access
- Author:
- Hafer, Kelsey
- Area of Honors:
- Veterinary and Biomedical Sciences
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Dr. Kumble Sandeep Prabhu, Thesis Supervisor
Dr. Kumble Sandeep Prabhu, Thesis Supervisor
Dr. Lester C Griel Jr., Thesis Honors Advisor - Keywords:
- 15d-PGJ3
inflammation
prostaglandin bioactivity
EPA metabolism
delta-12-PGJ3 - Abstract:
- There has been a recent upsurge of interest in the health benefits of fish oils, which are rich in omega-3 fatty acids such as eicosapentaenoic acid (EPA). These purported benefits, ranging from improved heart health to relief from arthritis, are likely due to the proven anti-inflammatory effects of omega-3’s. It was unclear, however, if it was EPA itself or rather one of its metabolic breakdown products that was causing the anti-inflammatory effects. Increased consumption of fish oils is known to increase incorporation of EPA into the side chains of phospholipid molecules in the cell membrane, displacing EPA’s omega-6 fatty acid analog, arachidonic acid (AA). When cells are exposed to pro-inflammatory stimuli, the fatty acids are cleaved from the phospholipids and processed by cyclooxygenase (COX) enzymes and then a succession of prostaglandin (PG) synthases. The metabolic products of AA include PGs of the 2-series, which are generally shown to be pro-inflammatory, while EPA metabolizes to PGs of the 3-series, many of which have anti-inflammatory properties. Research with 2-series prostaglandins has shown that some, most notably 15d-Δ12,14-PGJ2, have unexpected anti-inflammatory effects. This project is therefore centered around the hypothesis that the 3-series analogs of these PGs may have superior anti-inflammatory capabilities. High pressure liquid chromatography coupled to UV-mass spectrometry was used to isolate and characterize the metabolic products of the in vitro and cell culture conversion of EPA. The products 15d-Δ12,14-PGJ3 and Δ12-PGJ3 showed significant anti-inflammatory properties by mitigating expression of pro-inflammatory genes in macrophages. The results suggest that the cyclopentenone metabolites of EPA, which are endogenously produced, have potent anti-inflammatory capabilities by virtue of their chemical structures.