Parallel intestinal and liver injury during early cholestasis in the rat: Modulation by bile salts and antioxidants

Piero Portincasa, Ignazio Grattagliano, Mario Testini, Maria Lucia Caruso, David Q.H. Wang, Antonio Moschetta, Giuseppe Calamita, Michele Vacca, Anna Maria Valentini, Giuseppe Renna, Germana Lissidini, Giuseppe Palasciano

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Whereas long-term cholestasis results in intestinal alterations and increased permeability to hepatotoxins, the effect of short-term cholestasis is less known and was investigated in bile duct ligated (BDL) rats. In the intestinal mucosa, at Day 7 BDL, total glutathione and protein sulfhydryl contents had decreased, oxidized glutathione levels increased (P < 0.05 vs baseline), and a reduced epithelium thickness with dissolving crypt phenomena was observed in 40% of rats. At Day 10, total protein content, glutathione-related enzyme activities, and the transmural electrophysiological activity had decreased (-50%); by contrast, oxidized proteins doubled (P < 0.05), and histological changes were extended to 70% of rats. In vitro exposure to taurodeoxycholate at micellar concentrations determined dysepithelization in normal gut but dissolving crypt phenomena and necrosis in cholestatic bowels. In the liver, ongoing cholestasis was associated with early oxidative changes especially in mitochondria, where protein sulfhydryls were decreased and negatively correlated with glutathione-protein mixed disulfides (r = -0.807, P < 0.001). Daily oral administration of tauroursodeoxycholate, a hydrophilic bile salt, and glutathione to BDL rats improved intestinal histology, function, and redox state. In conclusion, short-term cholestasis results in distinctive functional, oxidative, and morphological changes of intestinal mucosa, determined increased vulnerability to toxic injury, and parallel hepatic oxidative damage.

Original languageEnglish (US)
Pages (from-to)1381-1391
Number of pages11
JournalFree Radical Biology and Medicine
Volume42
Issue number9
DOIs
StatePublished - May 1 2007
Externally publishedYes

Keywords

  • Bile duct ligation
  • Bile salts
  • Extrahepatic cholestasis
  • Glutathione
  • Intestinal mucosa
  • Mitochondria
  • Protein sulfhydryls
  • Protein-glutathione mixed disulfides
  • Ussing chamber

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Parallel intestinal and liver injury during early cholestasis in the rat: Modulation by bile salts and antioxidants'. Together they form a unique fingerprint.

  • Cite this

    Portincasa, P., Grattagliano, I., Testini, M., Caruso, M. L., Wang, D. Q. H., Moschetta, A., Calamita, G., Vacca, M., Valentini, A. M., Renna, G., Lissidini, G., & Palasciano, G. (2007). Parallel intestinal and liver injury during early cholestasis in the rat: Modulation by bile salts and antioxidants. Free Radical Biology and Medicine, 42(9), 1381-1391. https://doi.org/10.1016/j.freeradbiomed.2007.01.039