Morphological Characteristics of Prostaglandin Cytoprotection

Abstract

The term "cytoprotection" originally described the ability of prostaglandins, independent of their known antisecretory activity, to prevent macroscopic evidence of gastric injury induced in different animal models under various experimental conditions. Several recent reports have challenged this concept because the apparent macroscopic protection could not be confirmed microscopically. To determine whether prostaglandins do indeed possess cytoprotective properties, and if such effects are dependent on the dose and the route of prostaglandin administration, studies were performed using 16,16 dimethyl prostaglandin E2 (PGE2) and the known gastric damaging agent, ethanol. Fasted rats received either oral or subcutaneous PGE2 in doses of 10 or 20 micrograms/kg or equal volumes of saline. Thirty minutes later, animals were given a 1-ml oral bolus of 50% or 100% ethanol or an equal volume of saline. At 5 minutes to 24 hours following ethanol, animals were sacrificed, and tissues from the glandular portion of the stomach were removed for histologic quantification of injury. At 5 minutes following ethanol, PGE2 reduced the depth of injury, but had no protective effects against surface cell damage when compared with control animals. By 24 hours after ethanol, most of the PGE2-treated mucosa was repaired. Oral administration of 10 micrograms/kg PGE2 was more cytoprotective at 5 minutes after ethanol than when administered by subcutaneous injection. This relationship was not true for the 20 micrograms/kg dose. We conclude that cytoprotection can be confirmed histologically, but is limited primarily to the deep mucosa. The ability of PGE2 to enhance healing is probably related to the prevention of deep mucosal injury, which thereby allows epithelial reconstitution to occur. Lastly, the effectiveness of PGE2 as a cytoprotective agent is dose- and route-dependent.

Colloidal gold localization of type IV collagen in the extracellular matrix of rat gastric mucosa: Influence of alcohol and prostaglandin

“…2). As reported previously, tissue damage was time and alcohol concentration-dependent such that the most severe alcohol damage was observed in animals sacrificed 60 min after 100% ethanol exposure, and the least severe at 5 min after 50% ethanol exposure (Schmidt and Miller, 1988a).…”

“…Schmidt and Miller (1988a) have shown that even though severe surface damage occurs with both 50% ethanol and 100% ethanol, damage which includes the gastric gland cells is significantly higher after treatment with absolute alcohol. Such effects upon the depth of epithelial injury may also appear in alterations of the molecular components of the extracellular matrix.…”

“…Although the cause of the concentration-dependent decrease in binding of gold to type IV collagen following alcohol exposure is unknown, the higher concentration may either have destroyed the entire molecule or changed its structural conformation enough to induce further loss of antibody binding. Schmidt and Miller (1988a) have shown that even though severe surface damage occurs with both 50% ethanol and 100% ethanol, damage which includes the gastric gland cells is significantly higher after treatment with absolute alcohol. Such effects upon the depth of epithelial injury may also appear in alterations of the molecular components of the extracellular matrix.…”

Pharmacotherapy of Peptic Ulcer Disease and Latest Research

“…The term cytoprotection coined by Robert is defined as protection against gastric mucosal injury by mechanisms other than neutralisation of gastric acid [14]. An explosion of investigations led to the discovery that endogenous prostaglandins are involved in cytoprotection via putative mechanisms which includes mucus secretion, release of bicarbonate, maintenance and strengthening of mucosal blood flow and free radical scavenging [15][16][17][18]. The normal gastric mucosa without exogenous insult remains hostile to the acidic milieu of gastric lumen.…”