EICOSANOIDS in HUMAN PHYSIOLOGY: POLYUNSATURATED FATTY ACID SOURCES, BIOSYNTHESIS, FUNCTIONS, and THERAPEUTIC IMPLICATIONS

This comprehensive review explores the sources, biosynthesis, transport, and multifaceted functions of eicosanoids in human physiology. Eicosanoids, encompassing prostaglandins, thromboxanes, leukotrienes, lipoxins, and their oxygenated derivatives, are lipid mediators derived from C20 polyunsaturated fatty acids, primarily belonging to the omega-6 and omega-3 families. Arachidonic acid, a major precursor, serves as the primary building block for prostaglandins and other eicosanoids. It is stored in cell membrane phospholipids, predominantly in phosphatidylinositol and other complex lipid forms. The release of free arachidonic acid is facilitated by the enzyme phospholipase A2. Eicosanoids exert diverse biological functions within vertebrates, participating in crucial endocrine processes such as inflammation, reproduction, gastric secretion, and blood pressure regulation. Moreover, they contribute to homeostasis maintenance by modulating vascular permeability, safeguarding gastric mucosal integrity, and regulating platelet aggregation. Notably, eicosanoids exhibit both pro-inflammatory and anti-inflammatory properties, engaging in complex regulatory networks involving immune cells and the microenvironment. They also play significant roles in neural cell crosstalk, atherosclerosis, cancer development, platelet activation, and allergic/asthmatic diseases. Understanding the intricate mechanisms and interactions of eicosanoids holds great potential for targeted therapeutic interventions. Further research in this field can provide valuable insights into their precise roles and aid in the development of novel treatments for a wide range of diseases.

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  • 1. Bruegel M., Ceglarek U., Thiery J. Eicosanoids: essential mediators in health and disease/Eicosanoide: bedeutende Faktoren in der Homöostase und ihre Bedeutung in der Pathogenese multipler Erkrankungen. Aus Der Zeitschrift LaboratoriumsMedizin 2009;33(6):333–339. Doi: 10.1515/JLM.2009.056.
  • 2. David L. Nelson, Michael M. Cox Lehninger Principles of Biochemistry. 2017.
  • 3. De Caterina R., Basta G. n-3 Fatty acids and the inflammatory response-biological background. European Heart Journal Supplements 2001;3:42–49. Doi: 10.1016/S1520-765X(01)90118-X.
  • 4. Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 2001;294(5548):1871–5. Doi: 10.1126/science.294.5548.1871.
  • 5. Mosaad E., Peiris HN., Holland O., Morean Garcia I., Mitchell MD. The Role(s) of Eicosanoids and Exosomes in Human Parturition. Frontiers in Physiology 2020;11, 594313. Doi: 10.3389/fphys.2020.594313.
  • 6. Yamaguchi A., Botta E., Holinstat M. Eicosanoids in inflammation in the blood and the vessel. Frontiers in Pharmacology 2022;13, 997403. Doi: 10.3389/fphar.2022.997403.
  • 7. Strauss JF., FitzGerald GA. Chapter 4 - Steroid Hormones and Other Lipid Molecules Involved in Human Reproduction. In: Strauss JF, and Barbieri RL, editors. Yen and Jaffe’s Reproductive Endocrinology (Eighth Edition). Philadelphia: Elsevier; 2019. p. 75-114.e7.
  • 8. Tapiero H., Nguyen Ba G., Couvreur P., Tew KD. Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies. Biomedicine & Pharmacotherapy 2002;56(5):215–222. Doi: 10.1016/S0753-3322(02)00193-2.
  • 9. Whelan J., Surette M., Hardardottir I., et al. Dietary arachidonate enhances tissue arachidonate levels and eicosanoid production in Syrian hamsters. The Journal of Nutrition 1993;123:2174–2185. Doi: 10.1093/jn/123.12.2174.
  • 10. Caramia G. Essential fatty acids and lipid mediators. Endocannabinoids. La Pediatria Medica e Chirurgica 2012;34(2). Doi: 10.4081/pmc.2012.2.
  • 11. Prasad KN., Hovland AR., Cole WC., et al. Multiple Antioxidants in the Prevention and Treatment of Alzheimer Disease: Analysis of Biologic Rationale. Clinical Neuropharmacology 2000;23(1):2–13. Doi: 10.1097/00002826-200001000-00002.
  • 12. Smith WL., DeWitt DL., Garavito RM. Cyclooxygenases: Structural, Cellular, and Molecular Biology. Annu Rev Biochem 2000;69(1):145–182. Doi: 10.1146/annurev.biochem.69.1.145.
  • 13. Xu Y., Qian SY. Anti-cancer Activities of ω-6 Polyunsaturated Fatty Acids. Biomed J 2014;37(3):112–119. Doi: 10.4103/2319-4170.131378.
  • 14. Zulfakar MH., Edwards M., Heard CM. Is there a role for topically delivered eicosapentaenoic acid in the treatment of psoriasis? European Journal of Dermatology 2007;17(4):284–291. Doi: 10.1684/ejd.2007.0201.
  • 15. Duroudier NP., Tulah AS., Sayers I. Leukotriene pathway genetics and pharmacogenetics in allergy. Allergy 2009;64(6):823–839. Doi: 10.1111/j.1398-9995.2009.02015.x.
  • 16. Mazaleuskaya LL., Ricciotti E. Eicosanoid Pathway Modulators: Prostaglandins, Prostacyclin, and Thromboxane. Burger’s Medicinal Chemistry and Drug Discovery. John Wiley & Sons, Ltd; 2021. p. 1–54.
  • 17. Hanna VS., Hafez EAA. Synopsis of arachidonic acid metabolism: A review. Journal of Advanced Research 2018;11:23–32. Doi: 10.1016/j.jare.2018.03.005.
  • 18. Ueno N., Takegoshi Y., Kamei D., Kudo I., Murakami M. Coupling between cyclooxygenases and terminal prostanoid synthases. Biochemical and Biophysical Research Communications 2005;338(1):70–76. Doi: 10.1016/j.bbrc.2005.08.152.
  • 19. Bäck M., Dahlén S-E., Drazen JM., et al. International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions. Pharmacol Rev 2011;63(3):539–584. Doi: 10.1124/pr.110.004184.
  • 20. Tilley SL., Coffman TM., Koller BH. Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 2001;108(1):15–23. Doi: 10.1172/JCI13416.
  • 21. Alba MM., Ebright B., Hua B., et al. Eicosanoids and other oxylipins in liver injury, inflammation and liver cancer development. Frontiers in Physiology 2023;14, 1098467. Doi: 10.3389/fphys.2023.1098467.
  • 22. Cazevieille C., Muller A., Meynier F., Dutrait N., Bonne C. Protection by prostaglandins from glutamate toxicity in cortical neurons. Neurochem Int 1994;24(4):395–398. Doi: 10.1016/0197-0186(94)90118-x.
  • 23. Kuhn H., Chaitidis P., Roffeis J., Walther M. Arachidonic Acid metabolites in the cardiovascular system: the role of lipoxygenase isoforms in atherogenesis with particular emphasis on vascular remodeling. J Cardiovasc Pharmacol 2007;50(6):609–620. Doi: 10.1097/FJC.0b013e318159f177.
  • 24. Piper K., Garelnabi M. Eicosanoids: Atherosclerosis and cardiometabolic health. J Clin Transl Endocrinol 2020;19, 100216. Doi: 10.1016/j.jcte.2020.100216.
  • 25. Yacoubian S., Serhan CN. New endogenous anti-inflammatory and proresolving lipid mediators: implications for rheumatic diseases. Nat Clin Pract Rheumatol 2007;3(10):570–579. Doi: 10.1038/ncprheum0616.
  • 26. Hoxha M., Zappacosta B. CYP-derived eicosanoids: Implications for rheumatoid arthritis. Prostaglandins Other Lipid Mediat 2020;146, 106405. Doi: 10.1016/j.prostaglandins.2019.106405.
  • 27. Hoxha M. A systematic review on the role of eicosanoid pathways in rheumatoid arthritis. Advances in Medical Sciences 2018;63(1):22–29. Doi: 10.1016/j.advms.2017.06.004.
  • 28. Harizi H., Corcuff J-B., Gualde N. Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends Mol Med 2008;14(10):461–469. Doi: 10.1016/j.molmed.2008.08.005.
  • 29. Shen D., Deng C., Zhang M. Peroxisome proliferator-activated receptor gamma agonists inhibit the proliferation and invasion of human colon cancer cells. Postgrad Med J 2007;83(980):414–419. Doi: 10.1136/pmj.2006.052761.
  • 30. Davì G., Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007;357(24):2482–2494. Doi: 10.1056/NEJMra071014.
  • 31. Crescente M., Menke L., Chan MV., Armstrong PC., Warner TD. Eicosanoids in platelets and the effect of their modulation by aspirin in the cardiovascular system (and beyond). Br J Pharmacol 2019;176(8):988–999. Doi: 10.1111/bph.14196.
  • 32. Sokolowska M., Rovati GE., Diamant Z., et al. Current perspective on eicosanoids in asthma and allergic diseases: EAACI Task Force consensus report, part I. Allergy 2021;76(1):114–130. Doi: 10.1111/all.14295.