INFLAMMATION Part 5 Chemical Mediators ARACHIDONIC ACID METABOLITES

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Inflammation Part 5: ARACHIDONIC ACID METABOLITES • click to watch the earlier videos of inflammation • Inflammation 1: https://www.youtube.com/edit?o=U vide... • Inflammation 2: https://www.youtube.com/edit?o=U vide... • Inflammation 3: https://www.youtube.com/edit?o=U vide... • Inflammation 4: • INFLAMMATION Part 4: Chemical Mediato... • ARACHIDONIC ACID METABOLITES In Inflammation • 3. Overview • What are Arachidonic acid metabolites • How are they synthesized • The roles of these metabolites in inflammation • Applied Aspects ( Very Important!) • 4. Tissue injury Injury to Neutrophils , Mast cells, platelets, endothelial cells, Macrophages Influx of Calcium into these cells Activation of Phospholipase A2Arachidonic acid in membrane phospholipids of the above cells Free Arachidonic acid • 5. Once arachidonic acid is freed from the membrane, it is rapidly converted to bioactive mediators. These mediators are referred to as Eicosanoids ( derived from 20-carbon fatty acids) Eicosa is a greek word – Meaning 20 Prostaglandins, Thromboxane, Leukotrienes and lipoxins are the eicosanoids formed • 6. ARACHIDONIC ACID Cyclooxygenase Pathway 5- Lipooxygenase Pathway 5HPETE Prostaglandin G2 (PGG2) Prostaglandin H2 (PGH2) Tissue specific synthesases PGD2 PGE2 PGF2α PGI2 TXA2 Prostacyclin Thromboxane A2 COX-1 / COX-2 Leukotriene A4 Leukotriene C4 Leukotriene E4 Leukotriene D4 Leukotriene B4 5HETE Lipoxin B4Lipoxin A4 12- Lipoxy genase Hydroperoxyeicosatetraenoic acid • 7. Prostaglandins Leukotrienes Lipoxins Produced by mast cells, macrophages, endothelial cells and other cells Produced by Leukocytes and mast cells • 8. Effects of These mediators in inflammation • 9. VASODILATION VASOCONSTRICTION VASODILATION BRONCHOCONSTRICTIONBRONCHODILATION PLATELET AGGREGATION +_ CHEMOATTRACTANT INHIBITS CHEMOTAXIS • 10. In addition, Prostaglandins also mediate Pain and fever which are the important systemic manifestation of inflammation • 11. What did we understand so far?? • The metabolites of arachidonic acid i.e prostaglandins, leukotrienes and lipoxins mediates • Vasodilation • Vasoconstriction • Bronchodilatation • Bronchoconstriction • Platelet aggregation and inhibition • Chemoattraction • Inhibition of chemotaxis! CAN MEDIATE POSSIBLY EVERY STEP OF INFLAMMATION • 12. Applied Aspects! Since , these mediators can mediate possibly every step of inflammation Inhibition of the production of these mediators SUPRESS INFLAMMATION SO WHAT?? • 13. Inhibition Non Steroidal Anti inflammatory drugs (NSAIDS) Aspirin Ibuprofen Diclofenac Suppress Inflammation Reduce Pain Fever • 14. InhibitionZileuton 5-lipoxygenase inhibitor Bronchoconstriction Treatment of Bronchial Asthma

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