Arachidonic acid cascade and gastric mucosal injury, protection, and healing: topics of this decade.
Evidence that exogenous prostaglandins (PGs) prevent cell damage caused by noxious agents in vitro is now accepted by most investigators. Gastric mucosal cells produce PGs and leukotrienes (LTs). Endogenous PGs may play a crucial role in cell protection, as evidenced by the fact that indomethacin accelerates ethanol-induced damage to dispersed gastric cells and exogenous PG reverses it. Moreover, mild irritants (3% ethanol or 50 degrees C water) stimulate PG generation in cells and make them resistant to ethanol-induced injury, effects that are abolished by indomethacin. On the other hand, an inhibitor of 5-lipoxygenase prevents cell injury caused by ethanol and exogenous LTC4 aggravates it, indicating that LTs have opposite effects on PGs. Another important area of PG research is restitution of surface epithelium after damage, allowing study of mechanisms of mucosal healing. PGs may promote wound healing not only via protective effects but also via stimulatory effects on cell proliferation, angiogenesis, reconstruction of extracellular matrix, and anti-inflammatory effects. PG depletion during the healing of experimental gastric ulcer predisposes to future ulcer relapse. Therefore, endogenous PGs may affect both the quality of ulcer healing and speed of ulcer healing. Persistent infiltration of polymorphonuclear cells in the mucosal scar is the most prominent finding that indicates poor quality of ulcer healing in rats treated initially with indomethacin and thus depleted of PGs. Recent clinical findings suggest a relationship between the quality of ulcer healing and future ulcer relapse. Gastroprotective drugs, such as PG analogues and inducers of PG synthesis, should have a crucial role in promotion of improved quality of ulcer healing and thus reduction of future relapse.
Kobayashi
K
K
Third Department of Internal Medicine, Osaka City University Medical School, Japan.
Arakawa
T
T
D016718:Arachidonic Acid / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism*; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D011453:Prostaglandins; D016718:Arachidonic Acid