Drug-induced enteropathy characterized by lipid in macrophages

Abstract

Groups of 10 male Upjohn Sprague-Dawley rats were treated po for 1 week with the synthetic 2′-dodecyl glutaramide ester of erythromycin. Rats given 1000 mg/kg daily ate about one-half of normal food consumption and showed essentially no growth. Weight gains of rats given 300 and 500 mg/kg were proportionally less affected. No gross lesions were observed. Lipid droplets accumulated in macrophages in the lamina propria of the small intestine and in the sinusoids of the mesenteric lymph nodes, in Kupffer cells in the liver and in fixed macrophages in the spleen. In fixed frozen sections these droplets stained well with Oil Red O. Toluidine blue stained epoxy sections were most useful in studying the distribution of the droplets. No evidence of acid-fastness or autofluorescence was observed in paraffin sections. The droplets resembled neutral lipid under electron microscopic examination. They appeared to undergo a gradual membranous degradation at their surface. At 3 weeks post-treatment most of the droplets had disappeared. Small aggregated myeloid figures were also present in the cells of the lamina propria of the small intestine and occasionally in the absorptive cells. Parallel studies with erythromycin base and the 2′-dodecyl glutaramide moiety, separately and simultaneously, did not produce the lipid accumulations in macrophages. From the latter results, it appeared that the ester was absorbed unhydrolyzed and converted rapidly to a chylomicron-like droplet. The reduction of orally administered d-xylose in the urine to about one-quarter of that in control rats was suggestive of malabsorption. Steatorrhea could not be confirmed by fecal lipid analyses because of the lipid structure of the ester.