title: Conjugated linoleic acid protects against gliadin-induced depletion of intestinal defenses.
abstract: METHODS
  The involvement of oxidative stress in gluten-induced toxicity has been evidenced in vitro and in clinical studies but has never been examined in vivo. We recently demonstrated the protective activity of conjugated linoleic acid (CLA), which functions by the activation of nuclear factor erythroid 2-related factor2 (Nrf2), a key transcription factor for the synthesis of antioxidant and detoxifying enzymes (phase 2). Here, we evaluate the involvement of nuclear factor erythroid 2-related factor2 in gliadin-mediated toxicity in human Caco-2 intestinal cells and in gliadin-sensitive human leukocyte antigen-DQ8 transgenic mice (DQ8) and the protective activity of CLA.
  
  
  RESULTS
  Gliadin effects in differentiated Caco-2 cells and in DQ8 mice, fed with a gliadin-containing diet with or without CLA supplementation, were evaluated by combining enzymatic, immunochemical, immunohistochemical, and quantitative real-time PCR (qRT-PCR) assays. Gliadin toxicity was accompanied by downregulation of phase 2 and elevates proteasome-acylpeptide hydrolase activities in vitro and in vivo. Notably, gliadin was unable to generate severe oxidative stress extent or pathological consequences in DQ8 mice intestine comparable to those found in celiac patients and the alterations produced were hampered by CLA.
  
  
  CONCLUSIONS
  The beneficial effects of CLA against the depletion of crucial intestinal cytoprotective defenses indicates a novel nutritional approach for the treatment of intestinal disease associated with altered redox homeostasis.
authors.affiliation: Istituto di Scienze dell'Alimentazione, Consiglio Nazionale delle Ricerche (CNR-ISA), Avellino, Italy. p.bergamo@isa.cnr.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Bergamo
authors.forename: Marta
authors.initials: M
authors.lastname: Gogliettino
authors.forename: Gianna
authors.initials: G
authors.lastname: Palmieri
authors.forename: Ennio
authors.initials: E
authors.lastname: Cocca
authors.forename: Francesco
authors.initials: F
authors.lastname: Maurano
authors.forename: Rosita
authors.initials: R
authors.lastname: Stefanile
authors.forename: Marco
authors.initials: M
authors.lastname: Balestrieri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mazzarella
authors.forename: Chella
authors.initials: C
authors.lastname: David
authors.forename: Mauro
authors.initials: M
authors.lastname: Rossi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D018938:Caco-2 Cells; D002446:Celiac Disease / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D005903:Gliadin / Q000009:adverse effects / Q000633:toxicity*; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic; D007422:Intestines / Q000187:drug effects* / Q000502:physiology*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004798:Enzymes; D006683:HLA-DQ Antigens; D044243:Linoleic Acids, Conjugated; D051267:NF-E2-Related Factor 2; D005903:Gliadin; D011503:Transglutaminases; D046988:Proteasome Endopeptidase Complex