Induced mucosal penetration and transfer to portal blood of luminal horseradish peroxidase after exposure of mucosa of guinea pig small intestine to ethanol and lysolecithin.

The effect of luminal 150 mmol saline, 0.05-0.2% (w/v) lysolecithin, and 5-20% (v/v) ethanol was studied on the mucosal morphology of the proximal small intestine in conscious guinea pigs as well as on the mucosal penetration and transfer to portal venous blood of luminal horseradish peroxidase (HRP). No ultrastructural evidence of mucosal damage was identified in any of the lysolecithin-perfused animals compared with saline controls. Ten and 20% ethanol (v/v) resulted in the appearance of fluid-filled spaces between enterocytes and in cytoplasmic lipid deposits and an increased number of autophagic vesicles within the cells themselves. Tight junctions remained intact. These changes after luminal 5% ethanol (v/v) were much less conspicuous. In the presence of saline, luminal HRP was largely confined to the brush border. Both lysolecithin and ethanol (5% v/v) rapidly induced mucosal penetration of HRP which was seen in cytoplasmic vesicles within enterocytes, between enterocytes, and in the lamina propria. Peak portal venous blood levels of HRP studied in multiple samples over 3 hr were one log unit greater than saline controls. Absorption of HRP was proportional to the luminal concentration of lysolecithin in the range tested. These studies show that mucosal penetration and absorption of functional exogenous macromolecules may be induced, in the absence of morphological evidence of mucosal damage, by luminal constituents which may perturb the structure of enterocyte membranes.