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Spermine affects intestinal in vitro permeability to different-sized molecules in rats
Abstract:
The gut epithelial lining is normally an effective barrier to entry of luminal bacteria and macromolecules into the body and dietary polyamines may influence its function. Therefore, the effects of spermine on regional intestinal permeability to different-sized marker molecules in rats were investigated in Ussing diffusion chambers. Mucosal exposure to 1 mM spermine reduced the permeation of the marker Na-fluorescein in jejunum, expressed as the apparent permeability coefficient (Papp). In contrast, Papp for Na-fluorescein was increased by 10 mM spermine in ileum and by 50 mM spermine in both jejunum and ileum. No effects were observed on [51Cr]-EDTA permeability in any of the intestinal regions. For the larger marker molecules, bovine serum albumin (BSA) and FITC-dextran 71200 (FITC-D), mucosal exposure to 0.5 mM spermine reduced Papp in colon. Spermine (10 mM), increased Papp for FITC-D in all regions and for BSA only in ileum, while Papp for BSA was increased by 50 mM spermine in both jejunum and ileum. The effects of spermine on the intestinal permeability to different-sized molecules generally seemed to depend on the intestinal region and on the polyamine concentration; higher spermine concentrations (10-50 mM) enhanced, while lower (0.5-1 mM) decreased the permeability. These findings may be important when trying to modulate epithelial barrier functions, especially during barrier dysfunction.
Insights
Dietary polyamines like spermine can alter gut barrier function. Low spermine concentrations decreased intestinal permeability, while high concentrations increased it, depending on the molecule size and gut region.
Area of Science:
- Gastroenterology
- Physiology
- Molecular Biology
Background:
- The gut epithelium forms a critical barrier against pathogens and macromolecules.
- Dietary polyamines, such as spermine, are known to influence gut epithelial function.
- Understanding polyamine effects on intestinal permeability is crucial for managing gut barrier dysfunction.
Purpose of the Study:
- To investigate the effects of spermine on regional intestinal permeability in rats.
- To determine how different concentrations of spermine affect the passage of various-sized marker molecules across the gut lining.
- To explore the concentration-dependent and region-specific actions of spermine on intestinal barrier function.
Main Methods:
- Utilized Ussing diffusion chambers to measure intestinal permeability in rat jejunum, ileum, and colon.
- Assessed the permeation of different-sized marker molecules: Na-fluorescein, [51Cr]-EDTA, bovine serum albumin (BSA), and FITC-dextran (FITC-D).
- Administered varying concentrations of spermine (0.5 mM to 50 mM) to the mucosal side and measured apparent permeability coefficients (Papp).
Main Results:
- Low spermine concentrations (0.5-1 mM) generally reduced the permeability of smaller molecules (Na-fluorescein) in specific regions.
- Higher spermine concentrations (10-50 mM) increased the permeability of larger molecules (BSA, FITC-D) across all intestinal regions.
- Spermine's effects on permeability were molecule-size dependent and varied significantly between jejunum, ileum, and colon.
Conclusions:
- Spermine exhibits dual effects on intestinal permeability, decreasing it at low concentrations and increasing it at high concentrations.
- These findings highlight the complex role of spermine in regulating the gut epithelial barrier.
- Modulating spermine levels could be a potential strategy for managing conditions involving intestinal barrier dysfunction.