Effect of Experimental Acute Renal Failure on Barriers to Permeation of a Polar Drug in Rat Jejunum: An Electrophysiological Analysis

Shinji Yamashita, Mikio Masada, Tanekazu Nadai, Masafumi Takahashi, Akira Kobayashi, Yuji Kurosaki, Taiji Nakayama, Toshikiro Kimura

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The effect of experimental acute renal failure on the permeability and transport function of the intestinal membrane was analyzed in the isolated rat jejunum by using in vitro electrophysiological methods. The mucosal-to-serosal flux rate of sulfanilic acid (SA), which was used as a model of the polar drug, increased significantly in the membrane obtained from the rat with acute renal failure, indicating a reduction of the barrier function of the intestinal membrane. This effect of renal failure was neither dependent on the procedure used to induce the disease nor correlated with the extent of the disease state, shown by the level of blood urea nitrogen. Furthermore, it was clarified that the change in the permeability to SA occurred mainly in the transcellular pathway but not in the paracellular one. The electrical resistance of the jejunal membrane did not change in rats with acute renal failure. Thus, it was suggested that the structure of the tight-junctional portion of the epithelial layer remained unchanged, while the permeability of the cellular membrane was altered by the disease state. The activity of the intestinal membrane to transport Na+ or glucose might not be influenced by the disease state since the transmembrane potential difference and the short-circuit current of the membrane showed no significant change from their normal values.

Original languageEnglish
Pages (from-to)2538-2543
Number of pages6
JournalChemical and Pharmaceutical Bulletin
Volume36
Issue number7
DOIs
Publication statusPublished - Jan 1 1988

Keywords

  • acute renal failure
  • electrical resistance
  • isolated rat jejunum
  • membrane permeability
  • paracellular route
  • short-circuit current
  • sulfanilic acid
  • transcellular route

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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