Abstract
American Cyanamid compound CL 115,574, a synthetic analog of prostaglandin E1, is active orally in inhibiting gastric acid secretion and in protecting against gastric ulcers induced by stress, ethanol, and nonsteroidal anti-inflammatory drugs. CL 115,574 was administered to rats for 6 months and to dogs for 1 year. Diarrhea occurred in both species and transient hyperthermia was observed in dogs. In rats, the only gross finding related to treatment was limited to the gastric mucosa and consisted of a dose-related widening of the cuticular ridge in the mid (2 mg/kg/day) and high (20 mg/kg/day) dose groups. Microscopically, there was a proliferation of the cuticular ridge stratified squamous epithelium. Morphologic findings in the dogs showed a multifocal proliferation of the foveolar epithelium in the pyloric antrum. Neither species had atypical cellular changes associated with the proliferative process. Furthermore, the changes in the dog consisted of well differentiated cells and occurred without pseudostratification of cells and increased mitotic activity. The “pseudoproliferative” character of these changes may be the result of a prolonged life span of most cell types of the gastric mucosa. These tissue adaptations reflect a true manifestation of the cytoprotective effect of prostaglandin E1 on the gastric mucosa.