420 ENHANCED JEJUNAL MACROMOLECULAR ABSORPTION INDUCED BY SECONDARY BILE SALTS

This study concerns the deleterious effects of secondary bile salts, tauro-deoxycholate (TDCh)and deoxycholate (DCh), particularly on small intestinal macromolecular absorption. Rat jejunal segments (30-40 cm)were perfused in vivo with an isotonic NaCl-glucose solution (pH6.9)containing 0.5 g% of horseradish peroxidase (HRP)a macromolecular tracer,with 5mM TDCh or DCh or without bile salts (C). After 30 and 60 min serum HRP levels and cytochemical HRP localization were determined. Both TDCh and DCh induced a greater absorption of HRP than C: at 30 min TDCh .157± .005, DCh .439 ±.080 vs C .082 ± .010, and at 60 min TDCh .381 ± .061, DCh 1.001 ± .138 vs C .114 ± .011 (data=u/ml means ± SEM, p<.001). The most striking absorption of HRP was with DCh. Under light and electron microscopy HRP was demonstrable in the intercellular spaces between enterocytes, in the basement membranes, and capillaries of the lamina propria of the jejunum. In contrast, in C, HRP was confined to the microvillar brush border and endocytotic structures of enterocytes. DCh also produced ultrastructural damage including swollen mitochondria and vacuolization of membrane systems whereas TDCh did not alter the intestinal epithelium. These results indicate that high concentrations of secondary bile salts enhance macromolecular absorption and induce functional damage to the jejunal epithelium. Deconjugated bile salts are the most injurious.