Ultrastructural Aspects of Prostaglandin Cytoprotection in an Alcohol Injury Model

The effects of absolute ethanol (EtOH) and 16,16-dimethyl-prostaglandin E2 (PGE2) on the ultrastructure of rat gastric mucosa were assessed using standard electron microscopic techniques. Fasted rats were injected subcutaneously with 10 micrograms/kg body weight of PGE2 or saline. After 30 min, animals received orally 100% EtOH or an equal volume of saline. Gastric mucosa was sampled at 5 min and 1, 2, 8, and 24 h post-EtOH and tissues procured for scanning and transmission electron microscopy. Both mucosal epithelial and connective tissue compartments were assessed. At 5 min after EtOH, in saline-pretreated animals, tissues showed extensive destruction of epithelium and connective tissue; major breaks in the basal laminae were coincident with hemorrhage. Deep-lying epithelial cells and most of the basal lamina were spared in tissues exposed to PGE2 prior to EtOH, permitting nearly complete repair within 24 h. Restitution proceeded over small breaks or pleats of basal lamina but failed in regions of total destruction of this structure. These data indicate that PGE2 protects not only deep-lying epithelial cells from EtOH damage but associated connective tissue as well and that sparing of both compartments leads to orderly and rapid epithelial restitution.