The digestive tolerance of cholesterol absorption inhibitors, which requires a constant improvement, was the main purpose of this study. Given the known hypocholesterolemic and antiatherosclerotic properties of some steroid glycosides, we synthesized a series of sterol derivatives by coupling some phytosterols known to interact with sterol absorption and also to be poorly absorbed to a cationic group. The first derivative was a potent inhibitor of cholesterol absorption and a potent hypocholesterolemic agent in different animal models, but was responsible for severe gastro-intestinal side-effects. In order to control the tolerance of the newly synthesized compounds, cholesterol and taurocholate absorption were measured in the jejunum and in the ileum, respectively. The intestinal water and ionic transport and the estimation of histological changes in the intestinal mucosae were determined simultaneously. The in-situ isolated loop technique, in anaesthetized rats, allowed the simultaneous control of these three parameters which were used to select the best derivative, inhibitor of cholesterol absorption devoid of any deleterious effect, as seen via a three-dimensional representation. The results showed that it was possible to obtain a specific cholesterol absorption inhibitor without secretory and deleterious effects and suggested that the amphiphilic characteristics of the molecules were responsible for their deleterious effects on digestive tract.

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PubMedDate not supplied

Mannitol enhances intracellular calcium diffusion in the rat ileum--a hypothesis.

The addition of 92 or 136 mM mannitol to a modified saline solution that contained 1.25 mM Ca2+ led to a mannitol concentration-dependent increase in the amount of calcium absorbed in 1 h from 8 cm long ileal loops prepared from fasted male Sprague-Dawley rats, with body weights of 190 +/- 10 g. It is argued that this mannitol-enhanced movement of calcium out of the loop cannot have utilized the paracellular pathway, inasmuch as the luminal calcium concentration of the mannitol instillate decreased during the experiment, with a negative calcium gradient between luminal and body fluids. Instead it is proposed that uncomplexed mannitol and the uncharged calcium complex of mannitol entered the ileal cells. The uncomplexed intracellular mannitol would bind additional calcium that had crossed the brush border down its gradient. The increase in total intracellular calcium will raise the effective intracellular gradient and thereby amplify intracellular calcium diffusion. This in turn increases calcium absorption.

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PubMedDate not supplied

[Comparison of hydroelectrolytic exchange characterized by calculation of saturable fluxes at three levels of the rat intestine].

Using the everted sac technique, which responded, as expected, to VIP by an increase of the secretion and to glucose by an increase of the absorption, we compared the water and electrolyte movements in the jejunum, ileum and colon in rats. Identical iso-osmolar test-solutions containing increasing NaCl concentrations, placed on the serosal and mucosal sides, allowed us to quantify fluxes in the absence of initial gradient. The measured net Na and Cl fluxes were dissociated into their two components, a passive flux from serosa to mucosa and a saturable flux from mucosa to serosa. The parameters of the saturable transport, calculated for each of the intestinal parts, showed the highest J max for the ileum (58.5 microEq.g-1.h-1 for Na and 52.8 microEq.g-1.h-1 for Cl) and the lowest Km for the colon that had the highest affinity for sodium and chloride (Km 11.1 mM for Na and 7.8 mM for Cl). These data confirm the functional difference between the three intestinal parts, with an active absorption of Na and active secretion of Cl in the jejunum, an apparent coupled Na and Cl absorption in the ileum and an active absorption with high affinity for both Na and Cl in the colon.

Animals↗

PubMedDate not supplied