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Updated: Aug 17, 2026
Ex Vivo Intestinal Sacs to Assess Mucosal Permeability in Models of Gastrointestinal Disease
Published on: February 9, 2016
Passive permeability in experimental intestinal damage in rats
Abstract:
1. Experiments were performed to study the absorption of two simultaneously administered polar probes of different molecular size from closed intestinal loops in rats subjected to various mucosal structural lesions. 2. Absorption of mannitol (molecular radius approximately 0.40 nm) was significantly decreased in rats with villous atrophy and crypt hypoplasia induced by the cytostatic agent methotrexate. The absorption of lactulose (radius approximately 0.54 nm) was also decreased, in contrast to the increased absorption which was found in an earlier study when villous atrophy with crypt hyperplasia was induced by infection by a nematode. The effect of local damage to villous tips, produced by the intraluminal presence of a detergent, was to increase significantly the absorption of lactulose. 3. In conjunction with the findings of earlier studies, these results support the hypothesis that there are at least two routes for the permeation of polar molecules. Small molecules such as mannitol probably pass through numerous cellular pores with a maximum radius lying between 0.40 and 0.54 nm and absorption is closely related to mucosal surface area. Larger molecules such as lactulose are probably restricted to less numerous extracellular pathways and absorption may be related to cell shedding or other areas of mucosal damage.
Insights
Intestinal absorption of polar molecules depends on molecular size and mucosal integrity. Smaller molecules like mannitol use cellular pores, while larger molecules like lactulose utilize extracellular pathways, with absorption varying based on intestinal damage.
Area of Science:
- Gastroenterology
- Pharmacokinetics
- Molecular Biology
Background:
- Intestinal absorption mechanisms for polar molecules are not fully elucidated.
- Understanding permeation routes is crucial for drug delivery and disease understanding.
Purpose of the Study:
- To investigate the absorption of polar probes of different molecular sizes in rats with induced intestinal mucosal lesions.
- To differentiate absorption pathways for small versus large polar molecules.
Main Methods:
- Simultaneous administration of mannitol and lactulose in closed intestinal loops in rats.
- Induction of mucosal lesions using methotrexate, nematode infection, or detergent.
- Quantification of probe absorption under varying conditions of mucosal damage.
Main Results:
- Methotrexate-induced villous atrophy decreased absorption of both mannitol and lactulose.
- Detergent-induced villous tip damage increased lactulose absorption.
- Absorption of mannitol correlated with mucosal surface area, while lactulose absorption was linked to mucosal damage.
Conclusions:
- Evidence supports at least two distinct permeation routes for polar molecules in the intestine.
- Small molecules (e.g., mannitol) likely traverse cellular pores, dependent on surface area.
- Larger molecules (e.g., lactulose) may use extracellular pathways, influenced by cell shedding and mucosal damage.
