A morphological and histochemical study of a drug-induced enteropathy in the Alderley Park rat.

Two experiments were devised to produce an experimental enteropathy. In Experiment I, male Alderley Park rats were dosed daily by gavage with 20 mg/kg and 60 mg/kg of an antibacterial compound ICI 17,363. Animals were killed sequentially at daily intervals up to and including Day 9 to study the development of the enteropathy. In Experiment II rats were dosed daily with 60 mg/kg of the same compound. All animals were killed on Day 5 owing to a rapid development of the enteropathic condition. The duodenum was examined histologically and histochemically. Duodenal changes included vacuolation of columnar epithelial cells and villus stunting. There were marked reductions in mitotic activity in the crypt epithelial cells from Day 7 onwards (Experiment I) and almost total loss of hydrolytic and oxidative enzyme activity. In Experiment II the changes were more severe and haemorrhage and erosion of the duodenal mucosa were observed. The development of the enteropathic lesion appears to be due largely to the antimitotic effect of the compound, although a direct toxic effect upon the intestinal mucosa cannot be ruled out.