Absence of functional peroxisome proliferator-activated receptor-α enhanced ileum permeability during experimental colitis

Emanuela Mazzon, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review


The aim of the present study was to examine the role of endogenous peroxisome proliferator-activated receptor-α (PPAR-α) ligand on the permeability and structure of small intestine tight junctions (TJs) in an animal model of experimental colitis, induced by dinitrobenzene sulfuric acid (DNBS). Four days after colitis induction with DNBS, the ileal TJs were studied by means of transmission electron microscopy using lanthanum nitrate and immunohistochemistry of occludin, zonula occludens 1, and claudin 2. Administration of DNBS to wild-type mice induced colon injury associated with a significant increase of plasma and colon tumor necrosis factor-α levels and with a significant increase of ileal permeability. Distal colitis in mice induced an increase of TJ permeability throughout the entire small intestine, and the extent of alterations correlates with colonic damage. Small intestinal permeability was associated with the presence of apoptosis (evaluated by FAS ligand expression and terminal deoxynucleotidyltransferase-mediated UTP nick end labeling coloration), which was associated with a significantly increased expression of proapoptotic Bax and decreased ileum content of antiapoptotic Bcl-2. Absence of a functional PPAR-α gene in PPAR-α knockout mice resulted in a significant augmentation of all the above-described parameters. Taken together, our results clearly demonstrate that endogenous PPAR-α ligands reduced small intestinal permeability in experimental colitis through the regulation of apoptosis and TJ protein.

Original languageEnglish
Pages (from-to)192-201
Number of pages10
Issue number2
Publication statusPublished - Aug 2007


  • Dinitrobenzene sulfuric acid
  • Inflammation
  • Intestinal permeability
  • PPAR-α
  • TJ protein

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine


Dive into the research topics of 'Absence of functional peroxisome proliferator-activated receptor-α enhanced ileum permeability during experimental colitis'. Together they form a unique fingerprint.

Cite this