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Effect of pH on aflatoxin B1 transfer in the everted rat jejunum
Abstract:
The effect of varying mucosal pH (5, 7.4 and 8) on aflatoxin B1 (AFB1) transmural transfer was studied in the everted rat jejunum. The viability of the preparation was evaluated by: light microscopy; rate of glucose uptake by tissue from the mucosal fluid; content and distribution of water and electrolytes in the tissue; oxygen uptake by the tissue; and the intestinal permeability to [14C]sucrose. These parameters revealed the structural and functional integrity of the preparation, which was not affected by incubation in the presence of AFB1 or at different pH values in the mucosal fluid. The results obtained show that AFB1 was transferred to the serosal fluid and that the cumulative transfer was greater at pH 5 than at pH 7.4 or 8. In addition, AFB1 clearance, calculated from the slope of the plot of the cumulative amount of AFB1 transferred per unit of mucosal concentration vs. incubation time, indicated a very rapid accumulation by tissue and transfer of AFB1 to the serosal fluid. This process was also faster at pH 5. The integrity of the AFB1 molecule during incubation was shown by NMR spectra. The lack of metabolization of AFB1 during its translocation was demonstrated by TLC of the serosal fluid.
Insights
Mucosal pH significantly impacts aflatoxin B1 (AFB1) transfer across the jejunum. Lower pH levels (5) enhance AFB1 transmural transfer and tissue accumulation, with no observed AFB1 degradation.
Area of Science:
- Toxicology
- Gastroenterology
- Pharmacokinetics
Background:
- Aflatoxin B1 (AFB1) is a toxic metabolite with potential for intestinal absorption.
- Understanding the factors influencing AFB1 transmural transfer is crucial for assessing its toxicological risk.
Purpose of the Study:
- To investigate the effect of varying mucosal pH on AFB1 transmural transfer in an everted rat jejunum model.
- To assess the integrity of the jejunal preparation and the AFB1 molecule under experimental conditions.
Main Methods:
- Everted rat jejunum model used to study transmural transfer.
- Assessment of tissue viability through microscopy, glucose uptake, water/electrolyte content, oxygen uptake, and [14C]sucrose permeability.
- Analysis of AFB1 transfer to serosal fluid and calculation of AFB1 clearance.
- Confirmation of AFB1 integrity and lack of metabolization using NMR and TLC.
Main Results:
- Jejunal preparation maintained structural and functional integrity throughout the study.
- AFB1 was transferred from mucosal to serosal fluid.
- Cumulative AFB1 transfer and clearance were significantly greater at pH 5 compared to pH 7.4 and 8.
- AFB1 molecule integrity was confirmed, and no metabolization occurred during translocation.
Conclusions:
- Mucosal pH is a critical factor influencing AFB1 transmural transfer in the jejunum.
- Lowering mucosal pH enhances AFB1 absorption and tissue accumulation.
- The integrity of the AFB1 molecule is maintained during jejunal transfer, suggesting direct absorption rather than metabolic processing.