this file is all about eicosanoids including prostaglandins,prostacyclins and leukutriens with its mechanism of formation and inhibitors of LOX and COX pathways
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Arachidonic acid metabolites ppt pdf
1.
2. Islamic Republic of Afghanistan
Ministry of Higher Education
Ghalib university of Higher Education
Medical faculty
Supervised by: Dr.Zahra froq
Presenter: Mohammad Azizi
3. Introduction of arachidonic acid
Activation of PLA2
cyclic and linear pathway
COX and LOX inhibitors
NSAIDs
Therapeutic Uses of Eicosanoids
Eicosanoid vs hormones
Conclusion
References
Contents:
4. Arachidonic acid metabolites (Eicosanoids)
• The eicosanoids are considered "local hormones.“
• Eicosanoids have strong hormone-like actions in the
tissues where they are produced
They have specific effects on target cells close to their site of
formation.
They are rapidly degraded, so they are not transported to distal
sites within the body.
• Eicosanoids are not stored and are very unstable
• In humans, arachidonic acid is formed from linoleic
acid:
5. How And Where Is Arachidonic Acid Generated?How And Where Is Arachidonic Acid Generated?
10. Main sites of eicosanoid biosynthesis:
• Endothelial cells
• Leukocytes
• Platelets
• Kidney
• Unlike histamine, eicosanoids are NOT synthesized in advance and stored in
granules – when needed, they can be produced very quickly from arachidonate
released from membranes
11.
12. Cyclo-oxygenase Isoforms (COX-1 vs COX-2&cox-3):
three isoforms of COX
All produce prostaglandins (PGE2, PGF2a, PGI2)
COX-1 is constitutive, expressed in most tissues
physiological and homeostatic role, cell signalling
not influenced by steroid administration
not increased by cytokines nor bacteria
Continuously produce gastric mucosa, kidney ,platelets and vascular endothelial
cells
COX-2 is inducible following inflammation, trauma, etc
found in immunocompetent cells (e.g. leukocytes)
pathophysiological role, maintains inflammation
induced by cytokines (interleukin-1)
inhibited by steroids
COX-3 only in pathological conditions
13.
14. Biological role of leukotrienes :
LTs are produced mainly in leukocytes
Leukotrienes are very potent constrictors of the bronchial airway muscles: (LTC4,
LTD4, and LTE4)
They increase vascular permeability
They cause attraction (LTB4) and activation of leukocytes (primarily eosinophils and
monocytes), promote diapedesis , enhance phagocytosis
They regulate vasoconstriction
15. LTs in host defense :
(induction of gene
expression)
(activation of NADPH oxidase)
(synthesis of iNOS)
(release from neutrophils)
(receptors for LTs)
(LTs promote diapedesis,
delay apoptosis of
leukocytes)
16. BUT:
Overproduction of LTB4 was demonstrated in:
Crohn's disease
rheumatoid arthritis
psoriasis
cystic fibrosis
Leukotrienes are also suspected of participating in
atherosclerosis development
Excessive bronchoconstriction can be found in some forms of
asthma
17. In general, eicosanoids mediate:
inflammatory response, notably as it involves the joints (rheumatoid arthritis),
skin (psoriasis)
production of pain and fever
regulation of blood pressure
regulation of blood clotting
regulation of renal function
control of several reproductive functions, such as the induction of labor
24. They differ from hormones in the following aspects:
1.They are produced in small amounts in almost all tissues rather than
specialized glands.
2.They act locally rather than after transport to target tissues
3.They are not stored, have extremely short half life, and are metabolized rapidly
to inactive products at their site of synthesis.
4.Their biological effects are mediated by plasma and nuclear membrane
receptors, which are different in different organ systems.
25. • Induction of labour
• Therapeutic abortion
• On cardiovascular system
• Treatment of asthma
• Nose bleeding
Therapeutic Uses of Eicosanoids:
26. Conclusion:
Prostaglandins, thromboxane and leukotrienes are known as eicosanoids
They are produced in small amounts in almost all tissues,
act locally, and have many important physiological and pathological functions
The dietary precursor of eicosanoids is the essential fatty acid, linoleic acid
Synthesis of prostaglandins begins with oxidative cyclization
of free arachidonic acid to yield PGH2 by prostaglandin
endoperoxide synthase (cyclooxygenase)
There are two isozymes of the synthase: COX-1 and COX-2,
which are important drug targets