arbaprostil and Hyperplasia

The aim of the study was to examine the mitotic activity in the antral and duodenal epithelium of Sprague-Dawley rats given trophic doses of E2 prostaglandins during a prolonged period of time. Natural prostaglandin E2 (dose range: 0.2-5.0 mg.k-1) and 15 (R) 15 methyl prostaglandin E2 (dose range: 0.03-2.0 mg.kg-1) were administered for 11 days, and mitoses were arrested with vincristine for 4 h before estimation of the cumulative mitotic index. A dose-related hyperplasia of the antral glands was observed after treatment with prostaglandin E2 and the synthetic analogue (p less than 0.05). The proliferative zone was enlarged in rats treated with high doses of the analogue but natural prostaglandin E2 did not affect the limits of the proliferative zone. A dose-related reduction of the mitotic index was observed in animals treated with prostaglandin E2 despite the presence of hyperplastic changes. All doses of the analogue induced antral hyperplasia without affecting the mitotic index except in rats given the highest dose who had a significantly lower mitotic index than controls (p less than 0.05). Hyperplasia of both crypts and villi was observed in the duodenum of rats given high doses of E2 prostaglandins (p less than 0.05) whereas the mitotic index and the growth fraction were not affected by treatments. It is concluded that hyperplasia by prostaglandins is developed in absence of changes of the mitotic activity. The observed reduction of the mitotic index is interpreted as a secondary phenomenon, possibly mediated by a regulatory mechanism of cell proliferation which is triggered to reduce further epithelial growth. It is suggested that prostaglandin E2 might influence such regulatory mechanisms.

Topics: Administration, Oral; Animals; Arbaprostil; Cell Count; Dinoprostone; Duodenum; Gastric Mucosa; Hyperplasia; Mitosis; Prostaglandins E, Synthetic; Pyloric Antrum; Rats; Rats, Inbred Strains; Time Factors

The mucosal incorporation and clearance of a DNA precursor was examined in the rat stomach and intestine following oral treatment with natural prostaglandin E2 (PGE2) or 15(R) 15 methyl prostaglandin E2 (Me PGE2). Control groups received vehicle or pentagastrin. After five days of treatment animals were labelled with methyl-3H-thymidine. Groups of rats were killed at 0.75, 24, 72, 96 and 120 h after labelling. Treatments continued until killed. Mucosal scrapings were analysed for radioactivity and DNA. Morphometric measurements were performed and plasma levels of gastrin and somatostatin determined. PGE2 and its stable analogue produced hyperplasia within one week of treatment, in particular of the gastric antrum and changed the incorporation and clearance of radioactive thymidine from gastric and intestinal epithelia. The most consistent finding was a delayed elimination of thymidine from the mucosa, indicating a slowing of the DNA turnover. The DNA synthesis was differently affected along the gastrointestinal tract, being unchanged or reduced in the stomach and moderately increased in the intestine. Prostaglandin treatment was associated with a three- to ten-fold increase of the gastric acid contents and with elevated plasma levels of gastrin and somatostatin. It is concluded that E2 prostaglandins produce hyperplasia of gastric and intestinal epithelia in the rat by prolonging the cell survival time rather than by increasing new cell production. Hypergastrinemia is not a likely mediator of trophic actions of E2 prostaglandins, which develop despite elevated plasma levels of somatostatin.

Topics: Administration, Oral; Animals; Arbaprostil; Dinoprostone; DNA; Gastric Acid; Gastric Mucosa; Hormones; Hyperplasia; Intestinal Mucosa; Kinetics; Male; Prostaglandins E; Rats; Rats, Inbred Strains; Thymidine