3.5.3 Pharmacology I
Lab 9 Determination of anti-oedemic action of a NSAIDs (Aspirin) with the help of Plethysmometer (Cont'd...)
Side by side, the neutrophils migrate to the site of inflammation to phagocyte the invading organism. They stick to the pathogen with the help of adhesion molecules (selectins, integrins), activated by the innate immune system. Neutrophils release the lysosome, free radicals (superoxide, hypochloride anion, hydrogen per oxide) and defensins (physiological antibody) to destroy the pathogen as well as the affected tissues. As a consequence, the cellular debris phospholipids (PLs) are generated and phospholipase A2 (PL A2) gets activated to digest PLs. PLs is converted to arachidonic acid by PL A2. PLs is converted into platelet activating factor (PAF) by another enzyme named lyso-glyceryl phosphorylcholine. The free radicals are capable of activating the NF-$\kappa \beta$, which further induces the COX enzymes [Rang et. al., 2007, Tortora & Derrickson, 2011].
Arachidonic acid is metabolized by inducible COX-2 and lipoxygenase (5-LOX, 12-LOX & 15-LOX) enzymes. Among these, COX-2 converts arachidonic acid into different prostaglandins(PG D2, PG E2, PG I2 and PG F22$\alpha$) and thromboxane (TX A2). 5-LOX converts it into leukotrienes (LT E4 and cystenyl leukotrienes-LT B4, LT C4, LT D4). Cystenyl LTs further activate the TNF-$\alpha$ and IL-1 and thus provoke the inflammation. PG D2 and PG E2 stimulate the release of histamine from the mast cells and also release bradykinins [Rang et. al., 2007].
The signs and symptoms, associated to inflammation are caused by these mediators. TNF-$\alpha$, IL-1, PG D2, PG E2, PG I2 along with other mediators (histamines, PAF, LTs) cause vasodilatation of the affected area followed by increased blood flow to the site, which cause the oedema or swelling of the area [Rang et. al., 2007].
[Rang et. al., 2007] Rang H P, Dale M M, Ritter J M, Moore P K, Pharmacology, 5th Edition, Elsevier, pp. 217-160, 2007.
[Tortora & Derrickson, 2011] Tortora G and Derrickson B, Principles of anatomy and physiology, 13th Edition, Volume 2, John Willey and Sons, Inc, pp. 740, 2011.