Čes. slov. farm. 2012, 61(4):139-143
New pharmaceutical insights related to the pathways of PUFAs
- Katedra bunkovej a molekulárnej biológie liečiv, Univerzita Komenského v Bratislave, Farmaceutická fakulta, Slovenská republika
The fatty acyl structure represents the major lipid building block of practically all lipids and therefore is one of the most fundamental categories of these molecules. Fatty acids (FAs) differ particularly in their chain length, number of double bonds and position of the bonds in the chain. The number of double bonds in the unsaturated molecule of FA distinguishes monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs). In the living cell PUFAs represent the dominant substrates for the formation of biologically active compounds - octadecanoids, eicosanoids and docosanoids - classified as oxylipins or as PUFAnoids. The present review focuses only on the groups of PUFAnoids which biological activities comprise a "positive effect" for the cell. This group of omega-3 PUFAnoids consists of lipoxins, resolvins and protectins. All these biologically active lipids are formed mainly in the LOX-pathway. They are part of the cell mechanisms that contribute to the removal of inflammatory cells and restoration of tissue integrity. A new approach to an optimal anti-inflammatory model shows orientation to the dual COX/LOX-inhibition and the stimulation of the protective eicosanoids and docosanoids formation and its considerable therapeutic potential in managing of molecular mechanisms of chronic inflammatory processes.
Keywords: polyunsaturated fatty acids; lipoxins; resolvins; protectins
Received: May 30, 2012; Accepted: June 22, 2024; Published: April 1, 2012 Show citation
References
- Lobb K., Chow Ch. K. Fatty acid classification and nomenclature. In Chow, Ch.K. ed. Fatty acids in foods and their health implications, 3rd ed. Boca Raton: CRC Press 2007.
Go to original source...
- Fahy E., Subramaniam S., Brown H. A., Glass Ch. K., Merrill A. H. Jr.,, Murphy R. C., Raetz Ch. R. H., Russell D. W., Seyama Y., Shaw W., Shimizu T., Spener F., van Meer G., van Nieuwenhze M. S., White S. H., Witztum J. L., Dennis E. A. A comprehensive classification system for lipids. J. Lipid Res. 2005; 46, 839-862.
Go to original source...
Go to PubMed...
- Cunnane S. C. Problems with essential fatty acids time for a new paradigm? Prog. Lipid Res. 2003; 42, 544-568.
Go to original source...
Go to PubMed...
- Schaller F. Enzymes of the biosynthesis of octadecanoid-derived signalling molecules. J. Exp. Bot. 2001; 52, 11-23.
Go to original source...
- Kulkarni A. P. Lipoxygenase - a versatile biocatalyst for biotransformation of endobiotics and xenobiotics. Cell. Mol. Life Sci. 2001; 58, 1805-1825.
Go to original source...
Go to PubMed...
- Mukherjee P. K., Chawla A., Loayza M. S., Bazan N. G. Docosanoids are multifunctional regulators of neural cell integrity and fate significance in aging and disease. Prostaglandins Leukot. Essent. Fatty Acids 2007; 77, 233-238.
Go to original source...
Go to PubMed...
- Scher J. U., Pillinger M. H. 15d-PGJ2. The anti-inflammatory prostaglandin? Clin. Immunol. 2005; 114, 100-109.
Go to original source...
Go to PubMed...
- Christie W. W. Resolvins and protectins chemistry and biology. (18. 4. 2012).
- Kohli P., Levy B. D. Resolvins and protectins mediating solutions to inflammation. Brit. J. Pharm. 2009; 158, 960-971.
Go to original source...
Go to PubMed...
- Chiang N., Bermudez E. A., Ridker P. M., Hurwitz S., Serhan C. N. Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proc. Natl. Acad. Sci. USA 2004; 101, 15178-15183.
Go to original source...
Go to PubMed...
- Romano M. Lipid mediators lipoxin and aspirin-triggered 15-epi-lipoxins. Inflamm. Allergy Drug Targets 2006; 5, 81-90.
Go to original source...
Go to PubMed...
- Mirossay L., Mojžiš J. a kol. Základná farmakológia a farmakoterapia, Košice: Equilibria, 2006.
- Ferenčík M., Škárka B., Novák M., Turecký L. Biochémia, Bratislava: Slovak Academic Press, 2000.
- Serhan C. N., Petasis, N. A. Resolvins and protectins in inflammation resolution. Chem. Rev. 2011; 111, 5922-5943.
Go to original source...
Go to PubMed...
- Weylandt K. H., Chiu C. Y., Gomolka B., Waechter S. F., Wiedenmann B. Omega-3 fatty acids and their lipid mediators Towards an understanding of resolvin and protectin formation. Prostagl. Other Lipid Med. 2012; 97, 73-82.
Go to original source...
Go to PubMed...
- Bannenberg G., Serhan C. N. Specialized pro-resolving lipid mediators in the inflammatory response An update. Biochim. Biophys. Acta 2010; 1801, 1260-1273.
Go to original source...
Go to PubMed...
- Niemoller T. D., Bazan N. G. Docosahexaenoic acid neurolipidomics. Prostagl. Other Lipid Med. 2010; 91, 85-89.
Go to original source...
Go to PubMed...
- Seeds M. C., Bass D. A. Regulation and metabolism of arachidonic acid. Clin. Rev. Allergy Immunol. 1999; 17, 5-26.
Go to original source...
Go to PubMed...
- Gambaro G. Strategies to safely interfere with prostanoid activity while avoiding adverse renal effects could COX-2 and COX-LOX dual inhibition be the answer? Nephrol. Dial. Transplant. 2002; 19, 1159-1116.
Go to original source...
Go to PubMed...
- Sala A., Zarini S., Bolla M. Leukotrienes lipid bioeffectors of inflammatory reactions. Biochemistry (Mosc.) 1998; 63, 84-92.
- Martel-Pelletier J., Lajeunesse D., Reboul P., Pelletier J. P. Therapeutic role of dual inhibitors of 5-LOX and COX, selective and non-selective nonsteroidal anti-inflammatory drugs. Ann. Rheum. Dis. 2003; 62, 501-509.
Go to original source...
Go to PubMed...
- Serhan C. N., Levy B. D., Clish C. B., Gronert K., Chiang N. Lipoxins, aspirin-triggered 15-epi-lipoxin stable analogs and their receptors in antiinflammation a window for therapeutic opportunity. Ernst Schering Res. Found. Workshop 2000; 31, 143-185.
Go to original source...
Go to PubMed...
- Leone S., Ottani A., Bertolini A. Dual acting anti-inflammatory drugs. Curr. Top. Med. Chem. 2007; 7, 265-275.
Go to original source...
Go to PubMed...
- Vidal C., Gómez-Hernández A., Sánchez-Galán E., González A., Ortega L., Gómez-Gerique J. A., TuĖón J., Egido J. Licofelone, a balanced inhibitor of cyclooxygenase and 5-lipoxygenase, reduces inflammation in a rabbit model of atherosclerosis. J. Pharmacol. Exp. Therap. 2007; 320, 108-116.
Go to original source...
Go to PubMed...
- Fischer S. M., Klein R. D. Lipoxygenases as targets for cancer prevention. In Kelloff, G.J., Hawk, E.T., Sigman, C.C. eds. Cancer chemoprevention Promising cancer chemopreventive agents. New Jersey: Humana Press, 2004.
- Kramer B. C., Yabut J. A., Cheong J., Jnobaptiste R., Robakis T., Olanow C. E., Mytilineou C. Toxicity of glutathione depletion in mesencephalic cultures a role for arachidonic acid and its lipoxygenase metabolites. Eur. J. Neurosci. 2004; 19, 280-286.
Go to original source...
Go to PubMed...
- de Gatetano G., Donati M. B., Cerletti C. Prevention of thrombosis and vascular inflamation benefits and limitations of selective or combined COX-1, COX-2 and 5-LOX inhibitors. Trends Pharmacol. Sci. 2003; 24, 245-252.
Go to original source...
Go to PubMed...
- Bannenberg G., Arita M., Serhan C. N. Endogenous receptor agonists resolving inflammation. Sci. World J. 2007; 7, 1440-1462.
Go to original source...
Go to PubMed...