OHOHOHAktivasi neutrophilProduksi Free radicalInfiltra-tionO2-O2-O2-OHO2-XODHypoxamthine+O2O2Insult micro sirkulasiPelepasan elastase Insult pd endothelium pembuluh darahMuncul molecule adhesiveInsult mukosa lambungN S A I D - G a s t r i c M u c o s a I n j u r yIskemik - re-perfution

Hiraishi H et al., Mebio 1994;11(19):86 (Japanese)PhospholipaseLipoxygenaseCyclooxygenaseNSAIDsPhospholipidArachidonic acidDecrease of PGsDecrease mucosal defenseMucus reductionDecrease of HCO3- secretionMicrocirculation injuryGastric mucosal injuryIncrease of LTsIncrease free radicalsIschemia-reperfusionNeutrophil activationH+ dependent pathwayAccumulation in cellsDirectly damage cellsVasospasmLTC4LTD4LTB4LiposolubleInhibitionNSAIDs-induced gastric mucosal injuries

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N S A I D - mucosal damage

J M Seager. BMJ 2001

.J M Seager. BMJ 2001

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.J M Seager. BMJ 2001

J M Seager. BMJ 2001

John de Caestecker. BMJ 2001

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In Panel A are shown the critical amino acid residues in the substrate binding channel of sheep cyclooxygenase-1. His207 and His388 serve as distal and proximal ligands, respectively, of the heme group; Arg120 interacts with the carboxylate function of the fatty acid substrate and Ile523 participates in hydrophobic bonding; Tyr385 plays a role in free radical chemistry; and Ser530 is the target of acetylation by aspirin (see Figure 5). In Panel B is depicted the likely orientation of arachidonic acid in the binding channel. The carbons at which molecular oxygen is introduced are indicated

Comparison of NSAID Binding to Cyclooxygenase Isoforms