INFLAMMATION Part 5: Chemical Mediators: ARACHIDONIC ACID METABOLITES

Inflammation Part 5: ARACHIDONIC ACID METABOLITES

click to watch the earlier videos of inflammation
Inflammation 1: https://www.youtube.com/edit?o=U&video_id=gxUB7LEsZw4
Inflammation 2: https://www.youtube.com/edit?o=U&video_id=vl1Vt330wYY
Inflammation 3: https://www.youtube.com/edit?o=U&video_id=g287fB6NNUg
Inflammation 4: https://www.youtube.com/watch?v=Xdlihx4phEQ

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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