The role of arachidonic acid metabolites in inflammation

1. Inflammation
Part 5

2. 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

15. SUMMARY
• What are Arachidonic acid metabolites
• How are they synthesized
• The roles of these metabolites in inflammation
• Applied Aspects

16. THANKS FOR WATCHING
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