Morphological characteristics of prostaglandin cytoprotection.
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.
Schmidt
K L
KL
Department of Pathology, University of Texas Medical School, Houston 77225.
Miller
T A
TA
D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D000431:Ethanol / Q000633:toxicity; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D011453:Prostaglandins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011453:Prostaglandins; D000431:Ethanol; D015232:Dinoprostone