Mucosal adaptation to indomethacin induced gastric damage in man--studies on morphology, blood flow, and prostaglandin E2 metabolism.
The effect of 28 days' continuous administration of oral indomethacin on gastroduodenal morphology, gastric mucosal blood flow, and gastric mucosal prostaglandin E2 (PGE2) metabolism in man was studied to define further the mechanisms of mucosal injury induced by indomethacin. Indomethacin caused acute gastroduodenal damage in all cases, which was maximal at 24 hours of administration. With continued intake, mucosal adaptation occurs resulting in resolution of endoscopic mucosal damage. At the time of maximal mucosal damage, gastric mucosal blood flow was significantly reduced compared with values before treatment (p less than 0.001 in fundus and p less than 0.002 in antrum), with good correlation between the severity of damage and the magnitude of the reduction in blood flow (r = 0.76). Mucosal recovery was associated with a return of the blood flow to normal. PGE2 in mucosal homogenate was significantly reduced by indomethacin in both the fundus (p less than 0.01) and antrum (p less than 0.01) after 24 hours but there was no correlation between the magnitude of this reduction and the severity of mucosal damage (r = -0.34). Despite mucosal recovery by 28 days, PGE2 values remained significantly below those before treatment in both the fundus (p less than 0.01) and antrum (p less than 0.01). The PGE2 degradation capacity was not influenced by indomethacin. In conclusion, mucosal adaptation to acute damage by indomethacin occurs in man and seems independent of local PGE2 metabolism.
Shorrock
C J
CJ
University Department of Medicine, Queen Elizabeth Hospital, Birmingham.
Rees
W D
WD
D000222:Adaptation, Physiological / Q000187:drug effects*; D000328:Adult; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000473:pathology; D007583:Jejunum / Q000473:pathology; D008297:Male; D012039:Regional Blood Flow
D015232:Dinoprostone; D007213:Indomethacin