Evaluation of Mucosal Damage and Recovery in the Gastrointestinal Tract of Rats by a Penetration Enhancer
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To evaluate absorption barrier recovery in the gastrointestinal tract after treatment with a penetration enhancer by using a poorly absorbed marker and correlate results with morphological recovery.
Oral gavage of sodium dodecyl sulfate (SDS) was given to Wistar rats. Phenol red (PR) was given at different time points following administration of SDS. Blood samples were obtained from the jugular vein. Pharmacokinetic analysis was performed on the in vivo data using WinNonlin and MATLAB®5 software. The pharmacokinetic parameters of PR were compared to the negative control to measure functional recovery. The intestinal tissues were observed using light and transmission electron microscopy.
Absorption was highest when PR was co-administered with SDS. C max, AUC and K a decreased and T max and MAT increased as the recovery period (time between administration of SDS and PR) increased. The pharmacokinetic parameters approached the negative control profile in one hour after treatment with 1% SDS. Microscopy results showed recovery of paracellular and transcellular barrier at this time.
Absorption barrier recovery could be measured using a poorly absorbed marker. Functional recovery showed a good correlation with morphological recovery. The local effects of SDS were found to be temporary and reversible.
Key wordsabsorption enhancement mucosal damage mucosal recovery oral absorption penetration enhancers
- 8.T. Z. Csaky. Intestinal permeation and permeability: an Overview. In T. Z. Csaky (ed.), Pharmacology of Intestinal Permeation, Springer, New York, 1984, pp. 51–59.Google Scholar
- 18.Y. Choda, Y. Morimoto, H. Miyaso, S. Shinoura, S. Saito, T. Yagi, H. Iwagaki, and N. Tanaka. Failure of the gut barrier system enhances liver injury in rats: protection of hepatocytes by gut-derived hepatocyte growth factor. Eur. J. Gastroenterol. Hepatol 16:1017–1025 (2004).PubMedCrossRefGoogle Scholar
- 36.T. Murakami, Y. Sasaki, R. Yamajo, and N. Yata. Effect of bile salts on the rectal absorption of sodium ampicillin in rats. Chem. Pharm. Bull. (Tokyo) 32(5):1948–1955 (1984).Google Scholar
- 38.V. S. Chadwick, T. S. Gaginella, G. L. Carlson, J. C. Debongnie, S. F. Phillips, and A. F. Hofmann. Effect of molecular structure on bile acid-induced alterations in absorptive function, permeability, and morphology in the perfused rabbit colon. J. Lab. Clin. Med 94:661–674 (1979).PubMedGoogle Scholar
- 39.J. E. F. Reynolds (ed.). In Martindale, the extra pharmacopoeiaThe Royal Pharmaceutical Society of Great Britain, London, 1989, pp. 1555–1556.Google Scholar
- 43.A. Yamamoto, T. Uchiyama, R. Nishikawa, T. Fujita, and S. Muranishi. Effectiveness and toxicity screening of various absorption enhancers in the rat small intestine: effects of absorption enhancers on the intestinal absorption of phenol red and the release of protein and phospholipids from the intestinal membrane. J. Pharm. Pharmacol 48:1285–1289 (1996).PubMedGoogle Scholar
- 48.O. G. Fitzhugh, and A. A. Nelson. Chronic oral toxicities of surface-active agents. J. Am. Pharmacol. Assoc 37:29–32 (1948).Google Scholar
- 55.R. A. Argenizo, C. K. Henrikson, and J. A. Lisacos. Restitution of barrier and transport function of porcine colon after acute mucosal injury. Am. J. Physiol 255:G62–G71 (1988).Google Scholar
- 64.M. A. Hurni, A. B. Noach, M. C. Blom-Roosemalen, A. G. de Boer, J. F. Nagelkerke, and D. D. Breimer. Permeability enhancement in Caco-2 cell monolayers by sodium salicylate and sodium taurodihydrofusidate: assessment of effect-reversibility and imaging of transepithelial transport routes by confocal laser scanning microscopy. J. Pharmacol. Exp. Ther 267:942–950 (1993).PubMedGoogle Scholar
- 67.J. A. Matovel, R. B. Sund, and T. Landsverk. Morphological and functional recovery following exposure to deoxycholic acid. A study in the rat small intestine in vivo. APMIS 97:798–810 (1989).Google Scholar