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Rat Intestinal Dipeptidase Activity During Oral Neomycin and Gluten Administration

University of Pittsburgh, Department of Medicine and Veterans Administration Hospital, Pittsburgh, Pennsylvania

The mechanism of neomycin-induced azotorrhea and the role of dietary gluten were studied by measuring intestinal dipeptidase activity in rats given neomycin with or without dietary gluten. Rats fed a 10%-wheat-gluten—8%-casein diet or 18% casein (gluten-free) diet were given 100 mg neomycin daily by gastric tube for 7 days. Control groups were fed the appropriate diet, but no neomycin. Homogenates of intestinal mucosa were assayed for dipeptidase activity, using as substrates: glycyl-alanine, glycyl-L-leucine, glycyl-L-valine, DL-alanyl-glycine, glycyl-L-isoleucine, L-leucyl L-leucine, and DL-alanyl-L-leucine. Mean dipeptidase activity was significantly depressed only in the rats fed 10% gluten plus neomycin. Rats given neomycin and fed an 18%-casein (gluten-free) diet had normal intestinal dipeptidase activity. Neomycin inhibited gain in body weight in both experimental groups. The observed depression of dipeptidase activity may explain in part the increased fecal nitrogen excretion observed in man during neomycin administration. The experimental data indicate that neomycin in the presence of gluten partially inhibits intestinal dipeptidase activity.