title: Prostaglandin protection of the gastric mucosa against alcohol injury--a dynamic time-related process. Role of the mucosal proliferative zone.
abstract: 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.
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004573:Electrolytes / Q000378:metabolism; D000431:Ethanol / Q000037:antagonists & inhibitors*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005766:Gastrointestinal Contents / Q000032:analysis; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008938:Mitosis / Q000187:drug effects; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D004573:Electrolytes; D011459:Prostaglandins E, Synthetic; D000431:Ethanol; D015064:16,16-Dimethylprostaglandin E2