inflammation is a protective response of the body to cell injury caused by various factors (exposure to physical and chemical agents, pathogenic microorganisms, etc.). Such response aims to eliminate an exogenous pathogen, to prevent invasion of damaged tissue, and to restore tissue integrity. inflammation is a response triggered by damage to cell membranes leading to a cascade of events at the cellular level. in the beginning, phospholipids of fragments of a damaged membrane, under the influence of phospholipase A2, are transformed into arachidonic acid (fig. 15.1), which is a precursor of eicosanoids (signaling molecules) that regulate numerous important processes in the body, including inflammation.
There are three main pathways for arachi-donic acid metabolism.
• Participation of constitutively expressed cyclooxygenase-1 (COX-1) (see fig. 15.1) promotes formation of prostaglandins participating in physiological processes such as regulation of the renal blood flow, maintenance of a balance between production of hydrochloric acid and synthesis of protection factors (bicarbonates and mucus) in the stomach, regulation of platelet aggregation and microcirculation, uterine tone, etc.
• Activity of COX-2 expressed at the site of inflammation and subsequent formation of prostaglandins D2, E2, and i2, lead to local pain, swelling, hyperemia, and temperature rise.
• Arachidonic acid is a substrate for 5-lipoxy-genase enzyme which synthesizes other group of eicosanoids like leukotrienes, which belong to the family of eicosanoid inflammatory mediators and participate in the pathogenesis of some cardiovascular, respiratory diseases, and in the pathogenesis of allergy.
15.1. NONSTEROIDAL ANTIINFLAMMATORY DRUGS