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

34 Citations (Scopus)

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

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Cholestasis
Bile Acids and Salts
Liver
Rats
Antioxidants
Modulation
Glutathione
Bile Ducts
Ducts
Wounds and Injuries
Intestinal Mucosa
Proteins
Taurodeoxycholic Acid
Mitochondria
Histology
Glutathione Disulfide
Poisons
Enzyme activity
Disulfides
Oxidation-Reduction

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)

Cite this

Parallel intestinal and liver injury during early cholestasis in the rat : Modulation by bile salts and antioxidants. / Portincasa, Piero; Grattagliano, Ignazio; Testini, Mario; Caruso, Maria Lucia; Wang, David Q.H.; Moschetta, Antonio; Calamita, Giuseppe; Vacca, Michele; Valentini, Anna Maria; Renna, Giuseppe; Lissidini, Germana; Palasciano, Giuseppe.

In: Free Radical Biology and Medicine, Vol. 42, No. 9, 01.05.2007, p. 1381-1391.

Research output: Contribution to journalArticle

Portincasa, P, Grattagliano, I, Testini, M, Caruso, ML, Wang, DQH, Moschetta, A, Calamita, G, Vacca, M, Valentini, AM, 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, vol. 42, no. 9, pp. 1381-1391. https://doi.org/10.1016/j.freeradbiomed.2007.01.039
Portincasa, Piero ; Grattagliano, Ignazio ; Testini, Mario ; Caruso, Maria Lucia ; Wang, David Q.H. ; Moschetta, Antonio ; Calamita, Giuseppe ; Vacca, Michele ; Valentini, Anna Maria ; Renna, Giuseppe ; Lissidini, Germana ; Palasciano, Giuseppe. / Parallel intestinal and liver injury during early cholestasis in the rat : Modulation by bile salts and antioxidants. In: Free Radical Biology and Medicine. 2007 ; Vol. 42, No. 9. pp. 1381-1391.
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AU - Caruso, Maria Lucia

AU - Wang, David Q.H.

AU - Moschetta, Antonio

AU - Calamita, Giuseppe

AU - Vacca, Michele

AU - Valentini, Anna Maria

AU - Renna, Giuseppe

AU - Lissidini, Germana

AU - Palasciano, Giuseppe

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