Evaluation of Mucosal Damage and Recovery in the Gastrointestinal Tract of Rats by a Penetration Enhancer
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
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.
- D. C. Baumgart, and A. U. Dignass. Intestinal barrier function. Curr. Opin. Clin. Nutr. Metab. Care 5:685–694 (2002). CrossRef
- G. L. Eastwood. Gastrointestinal epithelial renewal. Gastroenterology 72:962–975 (1977).
- M. Lipkin. Proliferation and differentiation of gastrointestinal cells. Physiol. Rev 53:891–915 (1973).
- D. W. Powell. Barrier function of epithelia. Am. J. Physiol 241:G275–G288 (1981).
- A. L. Daugherty, and R. J. Mrsny. Regulation of the intestinal epithelial paracellular barrier. Pharm. Sci. Technol. Today 2:281–287 (1999). CrossRef
- K. L. Lutz, and T. J. Siahaan. Molecular structure of the apical junction complex and its contribution to the paracellular barrier. J. Pharm. Sci 86:977–984 (1997). CrossRef
- J. P. Kraehenbuhl, E. Pringault, and M. R. Neutra. Intestinal epithelia and barrier functions. Aliment. Pharmacol. Ther 11:3–8 (1997). CrossRef
- 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.
- A. Allen, G. Flemstrom, A. Garner, and E. Kivilaakso. Gastroduodenal mucosal protection. Physiol. Rev 73:823–857 (1993).
- E. Engel, P. H. Guth, Y. Nishizaki, and J. D. Kaunitz. Barrier function of the gastric mucus gel. Am. J. Physiol 269:G994–G999 (1995).
- M. Goke, and D. K. Podolsky. Regulation of the mucosal epithelial barrier. Baillieres Clin. Gastroenterol 10:393–405 (1996). CrossRef
- J. S. Trier. The surface coat of the gastrointestinal epithelial cells. Gastroenterology 56:618–624 (1969).
- J. Meyer-Kirchrath, and K. Schror. Cyclooxygenase-2 inhibition and side-effects of non-steroidal anti-inflammatory drugs in the gastrointestinal tract. Curr. Med. Chem 7:1121–1129 (2000).
- R. I. Russell. Protective effects of the prostaglandins on the gastric mucosa. Am. J. Med 81:2–4 (1986). CrossRef
- R. Rao, and F. Porreca. Epidermal growth factor protects mouse ileal mucosa from Triton X-100-induced injury. Eur. J. Pharmacol 303:209–212 (1996). CrossRef
- B. Montaner, M. Asbert, and R. Perez-Tomas. Immunolocalization of transforming growth factor-alpha and epidermal growth factor receptor in the rat gastroduodenal area. Dig. Dis. Sci 44:1408–1416 (1999). CrossRef
- H. Steiling, and S. Werner. Fibroblast growth factors: key players in epithelial morphogenesis, repair and cytoprotection. Curr. Opin. Biotechnol 14:533–537 (2003). CrossRef
- 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). CrossRef
- L. Thim. Trefoil peptides: from structure to function. Cell Mol. Life Sci 53:888–903 (1997). CrossRef
- A. Andoh, K. Kinoshita, I. Rosenberg, and D. K. Podolsky. Intestinal trefoil factor induces decay-accelerating factor expression and enhances the protective activities against complement activation in intestinal epithelial cells. J. Immunol 167:3887–3893 (2001).
- S. Fagarasan, and T. Honjo. Regulation of IgA synthesis at mucosal surfaces. Curr. Opin. Immunol 16:277–283 (2004). CrossRef
- S. J. Golby, and J. Spencer. Where do IgA plasma cells in the gut come from? Gut 51:150–151 (2002). CrossRef
- B. M. Myers, J. L. Smith, and D. Y. Graham. Effect of red pepper and black pepper on the stomach. Am. J. Gastroenterol 82(3):211–214 (1987).
- E. Jensen-Jarolim, L. Gajdzik, I. Haberl, D. Kraft, O. Scheiner, and J. Graf. Hot spices influence permeability of human intestinal epithelial monolayers. J. Nutr 128:577–581 (1998).
- T. Hoshino, N. Kashimoto, and S. Kasuga. Effects of garlic preparations on the gastrointestinal mucosa. J. Nutr 131(Suppl 3):1109S–1113S (2001).
- H. Amagase, B. L. Petesch, H. Matsuura, S. Kasuga, and Y. Itakura. Intake of garlic and its bioactive components. J. Nutr 131(Suppl 3):955S–962S (2001).
- P. R. Kvietys, R. D. Specian, M. B. Grisham, and P. Tso. Jejunal mucosal injury and restitution: role of hydrolytic products of food digestion. Am. J. Physiol 261:G384–G391 (1991).
- R. P. Bird, and W. R. Bruce. Effect of dietary calcium on the toxicity of bile acid and orally administered fat to colonic epithelium. Prog. Clin. Biol. Res 222:487–494 (1986).
- M. S. Millan, G. P. Morris, I. T. Beck, and J. T. Henson. Villous damage induced by suction biopsy and by acute ethanol intake in normal human small intestine. Dig. Dis. Sci 25:513–525 (1980). CrossRef
- E. R. Lacy, G. P. Morris, and M. M. Cohen. Rapid repair of the surface epithelium in human gastric mucosa after acute superficial injury. J. Clin. Gastroenterol 17(Suppl 1):S125–S135 (1993). CrossRef
- C. Aalykke, and K. Lauritsen. Epidemiology of NSAID-related gastroduodenal mucosal injury. Best Pract. Res. Clin. Gastroenterol 15:705–722 (2001). CrossRef
- J. L. Wallace. Pathogenesis of NSAID-induced gastroduodenal mucosal injury. Best Pract. Res. Clin. Gastroenterol 15:691–703 (2001). CrossRef
- J. F. Bretagne, N. Vidon, C. L’Hirondel, and J. J. Bernier. Increased cell loss in the human jejunum induced by laxatives (ricinoleic acid, dioctyl sodium sulphosuccinate, magnesium sulphate, bile salts). Gut 22:264–269 (1981). CrossRef
- K. J. Moriarty, M. J. Kelly, R. Beetham, and M. L. Clark. Studies on the mechanism of action of dioctyl sodium sulphosuccinate in the human jejunum. Gut 26:1008–1013 (1985). CrossRef
- D. R. Saunders, J. Sillery, and D. Rachmilewitz. Effect of dioctyl sodium sulfosuccinate on structure and function of rodent and human intestine. Gastroenterology 69:380–386 (1975).
- 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).
- A. Fasano, G. Budillon, S. Guandalini, R. Cuomo, G. Parrilli, A. M. Cangiotti, M. Morroni, and A. Rubino. Bile acids reversible effects on small intestinal permeability—an in vitro study in the rabbit. Dig. Dis. Sci 35:801–808 (1990). CrossRef
- 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).
- J. E. F. Reynolds (ed.). In Martindale, the extra pharmacopoeiaThe Royal Pharmaceutical Society of Great Britain, London, 1989, pp. 1555–1556.
- K. Hosoya, H. Kubo, H. Natsume, K. Sugibayashi, and Y. Morimoto. Evaluation of enhancers to increase nasal absorption using Ussing chamber technique. Biol. Pharm. Bull 17:316–322 (1994).
- E. S. Swenson, W. B. Milisen, and W. Curatolo. Intestinal permeability enhancement: efficacy, acute local toxicity, and reversibility. Pharm. Res 11:1132–1142 (1994). CrossRef
- M. Nakamaru, Y. Masubuchi, S. Narimatsu, S. Awazu, and T. Horie. Evaluation of damaged small intestine of mouse following methotrexate administration. Cancer Chemother.Pharmacol 41:98–102 (1998). CrossRef
- 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).
- K. Higaki, T. Yata, M. Sone, K. Ogawara, and T. Kimura. Estimation of absorption enhancement by medium-chain fatty acids in rat large intestine. Res. Commun. Mol. Pathol. Pharmacol 109:231–240 (2001).
- M. Sakai, T. Imai, H. Ohtake, and M. Otagiri. Cytotoxicity of absorption enhancers in Caco-2 cell monolayers. J. Pharm. Pharmacol 50:1101–1108 (1998).
- E. K. Anderberg, and P. Artursson. Epithelial transport of drugs in cell culture. VIII: effects of sodium dodecyl sulfate on cell membrane and tight junction permeability in human intestinal epithelial (Caco-2) cells. J. Pharm. Sci 82:392–398 (1993). CrossRef
- A. I. Walker, V. K. Brown, L. W. Ferrigan, R. G. Pickering, and D. A. Williams. Toxicity of sodium lauryl sulphate, sodium lauryl ethoxysulphate and corresponding surfactants derived from synthetic alcohols. Food Cosmet. Toxicol 5:763–769 (1967). CrossRef
- O. G. Fitzhugh, and A. A. Nelson. Chronic oral toxicities of surface-active agents. J. Am. Pharmacol. Assoc 37:29–32 (1948).
- H. Bohets, P. Annaert, G. Mannens, L. Van Beijsterveldt, K. Anciaux, P. Verboven, W. Meuldermans, and K. Lavrijsen. Strategies for absorption screening in drug discovery and development. Curr. Top. Med. Chem 1:367–383 (2001). CrossRef
- Y. Sambuy, I. De Angelis, G. Ranaldi, M. L. Scarino, A. Stammati, and F. Zucco. The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol.Toxicol 21:1–26 (2005). CrossRef
- P. Artursson, K. Palm, and K. Luthman. Caco-2 monolayers in experimental and theoretical predictions of drug transport. Adv. Drug Deliv. Rev 46:27–43 (2001). CrossRef
- A. Fasano, G. Budillon, S. Guandalini, R. Cuomo, G. Parrilli, A. M. Cangiotti, M. Morroni, and A. Rubino. Bile acids reversible effects on small intestinal permeability. An in vitro study in the rabbit. Dig. Dis. Sci 35:801–808 (1990). CrossRef
- 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).
- K. Masuda, H. Ikeda, K. Kasai, Y. Fukuzawa, H. Nishimaki, T. Takeo, and G. Itoh. Diversity of restitution after deoxycholic acid-induced small intestinal mucosal injury in the rat. Dig. Dis. Sci 48:2108–2115 (2003). CrossRef
- 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).
- J. A. Matovelo, T. Landsverk, and R. B. Sund. Alterations of ultrastructure and of cytoplasmic filaments in remodeling rat jejunal epithelial cells during recovery from deoxycholate. APMIS 98:887–895 (1990). CrossRef
- A. Jacinto, A. Martinez-Arias, and P. Martin. Mechanisms of epithelial fusion and repair. Nat. Cell Biol 3:E117–E123 (2001). CrossRef
- A. U. Dignass. Mechanisms and modulation of intestinal epithelial repair. Inflamm. Bowel Dis 7:68–77 (2001). CrossRef
- D. A. Waller, N. W. Thomas, and T. J. Self. Epithelial restitution in the large intestine of the rat following insult with bile salts. Virchows Arch. A Pathol. Anat. Histopathol 414:77–81 (1988). CrossRef
- K. Nakanishi, M. Masada, and T. Nadai. Effect of pharmaceutical adjuvants on the rectal permeability of drugs III. Effect of repeated administration and recovery of the permeability. Chem. Pharm. Bull 31:4161–4166 (1983).
- R. Moore, S. Carlson, and J. L. Madara. Villus contraction aids repair of intestinal epithelium after injury. Am. J. Physiol 257:G274–G283 (1989).
- S. Feldman, and M. Reinhard. Interaction of sodium alkyl sulfates with everted rat small intestinal membrane. J. Pharm. Sci 65:1460–1462 (1976). CrossRef
- D. A. Whitmore, L. G. Brookes, and K. P. Wheeler. Relative effects of different surfactants on intestinal absorption and the release of proteins and phospholipids from the tissue. J. Pharm. Pharmacol 31:277–283 (1979).
- 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).
- A. J. Hudspeth. Establishment of tight junctions between epithelial cells. Proc. Natl. Acad. Sci. U.S.A 72:2711–2713 (1975). CrossRef
- 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).
- 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).
- M. Riegler, R. Sedivy, W. Feil, G. Hamilton, B. Teleky, G. Bischof, E. Cosentini, T. Sogukoglu, R. Schiessel, and E. Wenzl. Laminin stimulates rapid epithelial restitution of rabbit duodenal mucosa in vitro. Scand. J. Gastroenterol 31:1167–1175 (1996). CrossRef
- Evaluation of Mucosal Damage and Recovery in the Gastrointestinal Tract of Rats by a Penetration Enhancer
Volume 25, Issue 1 , pp 25-38
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- absorption enhancement
- mucosal damage
- mucosal recovery
- oral absorption
- penetration enhancers
- Industry Sectors
- Author Affiliations
- 1. Product Development, Actavis, 10065 Red Run Blvd, Owings Mills, Maryland, 21117, USA
- 2. School of Pharmacy, University of Wisconsin-Madison, 777 Highland Ave., Madison, Wisconsin, 53705, USA
- 3. Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Dr Madison, Wisconsin, 53706, USA
- 4. Pediatrics, University of Wisconsin-Madison, 600 Highland Ave., Madison, Wisconsin, 53705, USA