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Evaluation of Viability of Excised Rat Intestinal Segments in the Ussing Chamber: Investigation of Morphology, Electrical Parameters, and Permeability Characteristics

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Abstract

Purpose. To clarify relations between alterations in electrical and permeability data with time and to elaborate accompanying structural changes of intestinal segments in Ussing chamber experiments.

Methods. Excised intestinal segments from the rat were studied in a modified Ussing chamber. Experiments were run up to 180 minutes during which the electrical parameters, PD, SCC, and R, were measured and the permeability coefficients (Papp) of mannitol and propranolol were determined. Each segment was observed under the light microscope for morphological evaluation.

Results. PD and SCC values showed a decrease for most segments while the R values remained steady throughout the experiment. The Papp for propranolol increased aborally to the small intestine. For mannitol, the reversed was observed. In some cases, there was a time-dependent change in permeability for these marker molecules. The main morphological changes observed were a decreased nucleo-apical distance, decreased villi amplification factor, initial edema, cell sloughing, and epithelial restitution.

Conclusions. The time-dependent changes in permeability coefficients of mannitol and propranolol are suggested to be related to changes in electrical parameters and morphological alterations. Presented data illustrates the importance of information regarding time-dependent structural changes for correct interpretation of permeability data.

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REFERENCES

  1. A-L. Ungell. (1997) Drug Dev and Ind Pharm 23:1-14.

    Google Scholar 

  2. T. T. Kararli. Gastrointestinal absorption of drugs. Crit. Rev. Therap. Drug Carrier Systems. 6:39-86 (1989).

    Google Scholar 

  3. P. Artursson, A.-L Ungell, and J.-E Löfroth. Selective paracellular permeability in two models of intestinal absorption: cultured monolayers of human intestinal epithelial cells and rat intestinal segments. Pharm. Res. 10:1123-1129 (1993).

    Google Scholar 

  4. R. L. Oberle, T. J. Moore, and D. A. P. Krummel. Evolution of mucosal damage of surfactants in rat jejunum and colon. J. Pharm. and Tox. Methods. 33:75-81 (1995).

    Google Scholar 

  5. A.-L Ungell, A. Andreasson, K. Lundin, and L. Utter. Effects of enzymatic inhibition and increased paracellular shunting on transport of vasopressin analogues in the rat. J Pharm. Sci. 81:640-645 (1992).

    Google Scholar 

  6. K. Palm, K. Luthman, A-L. Ungell, G. Strandlund, and P. Artursson. Correlation of drug absorption with molecular surface properties. J Pharm. Sci. 85:32-39 (1996).

    Google Scholar 

  7. R. B. Podesta and D. F. Mettrick. HCO3 transport in rat jejunum: relationship to NaCl and H2O transport in vivo. Am. J. Physiol. 232:E62-68 (1977).

    Google Scholar 

  8. R. B. Podesta and D. F. Mettrick. HCO −3 and H+ secretion in rat ileum in vivo. Am. J. Physiol. 232:E574-579 (1977).

    Google Scholar 

  9. J. Karlsson. Drug absorption in cell culture models of the intestinal epithelium. Doctoral thesis at Uppsala University, Department of Pharmacy, Division of Pharmaceutics (1995).

  10. M. Hemlin, M. Jodal, O. Lundgren, H. Sjövall, and L. Stage. The importance of the subepithelial resistance for the electrical properties of the rat jejunum in vitro. Acta Physiol. Scand. 134:79-88 (1988).

    Google Scholar 

  11. D. W. Powell. Barrier function of epithelia. Am. J. Physiol. 241:G275-G288 (1981).

    Google Scholar 

  12. C. K. Henrikson, R. A. Argenzio, J. A. Liacos, and J. Khosla. Morphologic and functional effects of bile salt on the porcine colon during injury and repair. Lab. Invest. 60:72-87 (1989).

    Google Scholar 

  13. J. J. Rafter, V. W. S. Eng, R. Furrer, A. Medline, and W. R. Bruce. Effects of calcium and pH on the mucosal damage produced by deoxycholic acid in the rat colon. Gut. 27:1320-1329 (1986).

    Google Scholar 

  14. A. B. R. Thomson, M. Keelan, M. T. Clandinin, and K. Walker. Dietary fat selectively alters transport properties of rat jejunum. J. Clin. Invest. 77:279-288 (1986).

    Google Scholar 

  15. J. A. Fix, K. Engle, P. A. Porter, P. S. Leppert, S. J. Selk, C. R. Gardner, and J. Alexander. Acylcarnitines: drug absorption-enhancing agents in the gastrointestinal tract. Am. J. Physiol. G332-G340 (1986).

  16. H. J. G. Gundersen, T. F. Bendtsen, L. Korbo, N. Marcussen, A. Moller, K. Nielsen, J. R. Nyengaard, B. Pakkenberg, F. B. Sorensen, A. Vesterby, and M. J. West. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. Recent stereological developments for pathology. 96:379-394 (1988).

    Google Scholar 

  17. G. R. Davis, C. A. Santa Ana, S. G. Morawski, and J. S. Fordtran. Permeability characteristics of human jejunum, ileum, proximal colon and distal colon: results of potential difference measurements and unidirectional fluxes. Gastroenterology. 83:844-850 (1982).

    Google Scholar 

  18. A. Collett, D. Walker, E. Sims, Y.-L. He, P. Speers, J. Ayrton, M. Rowland, and G. Warhurst. Influence of morphometric factors on quantitation of paracellular permeability of intestinal epithelia in vitro. Pharm. Res. 14:767-773

  19. A. Strocchi and M. D. Levitt. Role of villus surface area in absorption. Dig. Dis. Sci. 38:385-387 (1993).

    Google Scholar 

  20. G. T. A. McEwan and M. L. Lucas. The effect of E. coli STa enterotoxin on the absorption of weakly dissociable drugs from rat proximal jejunum in vivo. Br. J. Pharmacol. 101:937-943 (1990).

    Google Scholar 

  21. R. A. Argenzio, C. K. Henrikson, and J. A. Liacos. Effect of prostaglandin inhibitors on bile salt-induced mucosal damage of porcine colon. Gastroenterology 96:95-109 (1989).

    Google Scholar 

  22. A. Nusrat, C. A. Parkos, T. W. Liang, D. K. Carnes, and J. L. Madara. Neutrophil migration across model intestinal epithelia: monolayer disruption and subsequent events in epithelial repair. Gastroenterology 113:1489-1500 (1997).

    Google Scholar 

  23. R. Moore, S. Carlson, and J. L. Madara. Rapid barrier restitution in an in vitro model of intestinal epithelial injury. Lab Invest. 60:237-244 (1989).

    Google Scholar 

  24. J. L. Madara. Maintenance of the macromolecular barrier at cell extrusion sites in intestinal epithelium: physiological rearrangement of tight junctions. J. Membrane Biol. 116:177-184 (1990).

    Google Scholar 

  25. T. M. Mayhew and C. Middleton. Crypt, villi and microvilli in the small intestine of the rat. A stereological study of their variability within and between animals. J. Anat. 141:1-17 (1985).

    Google Scholar 

  26. R. Stenling and H. F. Helander. Stereological studies on the small intestinal epithelium of the rat. Cell Tissue Res. 217: 11-21 (1981).

    Google Scholar 

  27. T. M. Mayhew. Stereology: progress in quantitative microscopical anatomy. In V. Navaratnam and R. J. Harrison (eds.), Progress in anatomy, Cambridge University Press, Cambridge, 1983, pp. 81-112.

    Google Scholar 

  28. M. A. Marcial, S. L. Carlson, and J. L. Madara. Partitioning of paracellular conductance along the ileal crypt-villus axis: a hypothesis based on structural analysis with detailed consideration of tight junction structure-function relationships. J. Membrane Biol. 80:59-70 (1984).

    Google Scholar 

  29. M. J. Bastie, D. Balas, J. Laval, F. Senegas-Balas, C. Bertrand, C. Frexinos, and A. Ribet. Histological variations of jejunal and ileal mucosa on days 8 and 15 after hypophysectomy in rat: morphometrical analysis in light and electron microscope. Acta anat. 112:321-337 (1982).

    Google Scholar 

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Authors and Affiliations

  1. Biopharmaceutics, Pharmaceutical R & D, Astra Hässle AB, 431 83, Mölndal, Sweden

    Britta I. Polentarutti

  2. Cell Biology & Biochemistry, Preclinical R & D, Astra Hässle AB, 431 83, Mölndal, Sweden

    Anders L. Peterson

  3. Pharmacokinetics & Drug Metabolism, Preclinical R & D, Astra Hässle AB, 431 83, Mölndal, Sweden

    Åsa K. Sjöberg, Lena M. Utter & Anna-Lena B. Ungell

  4. Pharmaceutical Project Management, Pharmaceutical R & D, Astra Hässle AB, 431 83, Mölndal, Sweden

    Eva Karin I. Anderberg

Authors
  1. Britta I. Polentarutti
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  2. Anders L. Peterson
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  3. Åsa K. Sjöberg
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  4. Eva Karin I. Anderberg
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  5. Lena M. Utter
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  6. Anna-Lena B. Ungell
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Correspondence to Anna-Lena B. Ungell.

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Polentarutti, B.I., Peterson, A.L., Sjöberg, Å.K. et al. Evaluation of Viability of Excised Rat Intestinal Segments in the Ussing Chamber: Investigation of Morphology, Electrical Parameters, and Permeability Characteristics. Pharm Res 16, 446–454 (1999). https://doi.org/10.1023/A:1018890106045

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