Prostaglandin protection of the gastric mucosa against alcohol injury--a dynamic time-related process. Role of the mucosal proliferative zone.

The aim of the present study was first to resolve controversies regarding the extent of prostaglandin protection ("cytoprotection") of the gastric mucosa against injury produced by 100% ethanol and second to determine time sequence and histologic, ultrastructural, and functional features of this protection. Fasted rats received intragastrically (A) 0.9% NaCl alone as a control, (B) 5 micrograms/kg of 16,16-dimethyl prostaglandin E2 dissolved in 0.9% NaCl, and (C) 100 micrograms/kg of 16,16-dimethyl prostaglandin E2 dissolved in 0.9% NaCl. Thirty minutes later, 2 ml of 100% ethanol was instilled. The gastric mucosa was assessed macroscopically, by quantitative histology, and by scanning and transmission electron microscopy for [3H]thymidine uptake, mitotic activity, ion fluxes, and gastric potential difference determined at several time intervals (between 10 min and 16 h) after ethanol administration. Between 10 min and 16 h after ethanol administration macroscopic necrosis involved 27% +/- 3% to 41% +/- 4% of the mucosal area in controls (group A), but necrosis was prevented in groups receiving 16,16-dimethyl prostaglandin E2 (groups B and C). In the control group, histology and electron microscopy showed extensive disruption of the surface epithelium and deep necrosis (greater than 0.2 mm) involving greater than 46% +/- 4% of the mucosa between 15 min and 16 h after ethanol administration. Deep necrotic lesions were completely prevented by either dose of 16,16-dimethyl prostaglandin E2 (groups B and C). The mucosal proliferative zone was severely damaged in controls (68% +/- 5%) within the first hour after ethanol administration, whereas 16,16-dimethyl prostaglandin E2 protected the zone from damage (less than 5% +/- 1%). Neither dose of 16,16-dimethyl prostaglandin E2 prevented the occurrence of initial (at 15-30 min) morphologic and functional disruption of the surface epithelium after ethanol administration. However, initial disruption of the surface epithelium by 16,16-dimethyl prostaglandin E2 (groups B and C) was followed by migration of cells from the mucosal proliferative zone; the result was prompt restoration of the surface epithelium and resumption of its barrier and transport functions.