Mechanisms of mucosal injury and healing: the role of non-steroidal anti-inflammatory drugs.
Biological insights into injurious effects of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin (ASA), on mucosal protection and repair, are largely from studies of acute injury. That chronic ulceration is similar is not established. NSAIDs directly injure tissues, including endothelia, and at the same time impair the operation of many of the processes that normally contribute to mucosal protection, whatever the injurious agent. Many protective processes are mediated through prostaglandins, whose synthesis is abolished by inhibition of the constitutive isoenzyme, cyclooxygenase I (COX I) or Prostaglandin H-Synthase1 (PGHS1). The aims of therapy are aimed at inhibiting the inducible isozyme cyclooxygenase II (COX II) or prostaglandin-H Synthase2 (PGHS2), which contributes to prostanoid synthesis at sites of inflammation. Newer NSAIDs, selectively inhibiting COX II, promise to revolutionize the treatment of inflammatory disease while reducing mucosal injury. Meanwhile, there is increasing evidence that direct injury to both mucosae and endothelia is mediated by free-radical species, exacerbated by reduced blood flow, and by the local release of inflammatory and other mediators, which accentuate vascular leakage and hemorrhage, and cause intravascular aggregation of blood elements, stasis, hypoxia, and additional free-radical injury. The NSAIDs also inhibit epithelial cell division and the angiogenesis critical to healing and repair.
McCarthy
D M
DM
Division of Gastroenterology, University of New Mexico, Albuquerque, USA.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects; D006801:Humans; D008833:Microcirculation / Q000187:drug effects; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin