Cellular Aspects of Alcohol-Induced Injury and Prostaglandin Protection of the Human Gastric Mucosa

Abstract

In healthy volunteers, we studied the cellular target sites of alcohol-induced gastric mucosal injury and prostaglandin-induced protection with special emphasis on the mucosal microvascular ultrastructure. Subjects received pretreatment with saline or 16,16-dimethyl-prostaglandin E2 1 micrograms/kg b.w. and 15 min later 40 ml of 60% alcohol were sprayed on the gastric mucosa through an endoscope. Mucosal biopsies were obtained at 15 and 30 min after alcohol administration for assessment of injury by light and transmission electron microscopy. Alcohol administration to saline-pretreated subjects produced severe damage to gastric mucosal microvascular endothelium. Injury consisted of rupture of the microvessels with formation of intramucosal hemorrhages, platelet aggregation and fibrin deposition, and on occasion total necrosis of the microvessels. In contrast, in the prostaglandin-pretreated group, alcohol-induced damage to the mucosal microvessels and hemorrhages were greatly reduced at both 15 and 30 min after alcohol administration. In separate group of subjects, we investigated the effect of prostaglandin alone (without alcohol) on the gastric mucosal microvessel ultrastructure. We found that prostaglandin produced prominent ultrastructural changes in the capillaries, which may be the basis for its protective action. This study demonstrated that the human gastric mucosal microvasculature is an important target site of alcohol injury and prostaglandin protection. The direct effect of prostaglandin on endothelial ultrastructure may render it more resistant to alcohol injury. While protection of the endothelial cell lining of the mucosal microvasculature represents an example of a broader phenomenon of protective action of prostaglandin on various cells, the crucial strategic role of the microvasculature makes preservation (protection) of its integrity of special importance for the gastric mucosa.