The anti-inflammatory effect of colchicine in gout is primarily mediated by which subcellular mechanism?
- A Inhibition of prostaglandin synthesis by blocking COX-1 and COX-2
- B Blockade of P-selectin on endothelial cells preventing neutrophil rolling
- C Direct scavenging of free uric acid crystals in synovial fluid
- D Binding to beta-tubulin, preventing microtubule polymerisation and inhibiting neutrophil migration and NLRP3 inflammasome assembly ✓
Explanation
Colchicine binds to tubulin heterodimers (beta-tubulin at the colchicine site) and prevents their polymerisation into microtubules. This disrupts multiple neutrophil functions: chemotaxis (impairs cell motility), degranulation (secretory vesicle transport requires intact microtubules), and notably NLRP3 inflammasome assembly (which requires cytoskeletal reorganisation), thereby blocking IL-1β processing. Colchicine also inhibits the formation of superoxide by neutrophils. It has no direct effect on COX, does not block P-selectin (that is fucoidan's mechanism), and cannot dissolve uric acid crystals.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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