title: Adaptive response activated by dietary cis9, trans11 conjugated linoleic acid prevents distinct signs of gliadin-induced enteropathy in mice.
abstract: OBJECTIVE
  The beneficial effects of conjugated linoleic acid (CLA) mixture (cis9, trans11, c9; trans10, cis12, t10) against gliadin-induced toxicity in HLA-DQ8-transgenic mice (DQ8) have been associated with improved duodenal cytoprotective mechanisms [nuclear factor-E2-related factor-2, Nrf2; acylpeptide hydrolase (APEH)/proteasome]. The present study was aimed at investigating the ability of individual CLA isomers to improve the efficacy of these defensive mechanisms and to protect against duodenal injury caused by the combined administration of gliadin and indomethacin (GI).
  
  
  METHODS
  Gluten-mediated enteropathy was induced in DQ8 mice by three intra-gastric administration of gliadin (20 mg kg(-1)/bw) and indomethacin (15 mg L(-1)) in drinking water for 10 days (GI). C9 or t10 CLA (520 mg kg(-1)/bw/day) were orally administered for 2 weeks. Pro-oxidant and toxic effects associated with GI treatment, anti-oxidant/detoxifying ability of c9 or t10-CLA and the protective effect induced by c9 pre-treatment (c9 + GI) were evaluated in DQ8 mice duodenum by combining enzymatic, immunoblotting, histological evaluation and quantitative real-time PCR assays.
  
  
  RESULTS
  GI treatment produces the time-dependent decline of the considered detoxifying mechanisms thus leading to pro-apoptotic and pro-oxidant effects. APEH/proteasome pathway was not markedly affected by individual CLA isomers, but duodenal redox status and activity/mRNA levels of Nrf2-activated enzymes were significantly improved by c9 administration. c9 pre-treatment protects against GI-mediated accumulation of oxidative stress markers, and histological examination reveals the increase of goblet cells number in mouse duodenum but induces only a partial recovery of APEH/proteasome activity.
  
  
  CONCLUSIONS
  The activation of and adaptive response by low doses of c9 supplementation prevents distinct signs of gliadin-induced enteropathy in DQ8 mice.
authors.affiliation: Institute of Food Sciences, National Research Council (CNR-ISA), Via Roma 64, 83100, Avellino, Italy. p.bergamo@isa.cnr.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bergamo
authors.affiliation: Institute of Biosciences and Bioresources, National Research Council (CNR-IBBR), Naples, Italy.
authors.forename: Gianna
authors.initials: G
authors.lastname: Palmieri
authors.affiliation: Institute of Biosciences and Bioresources, National Research Council (CNR-IBBR), Naples, Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: Cocca
authors.affiliation: Department of Biology, University "Federico II" of Naples, Naples, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Ferrandino
authors.affiliation: Institute of Biosciences and Bioresources, National Research Council (CNR-IBBR), Naples, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Gogliettino
authors.affiliation: Department of Biology, University "Federico II" of Naples, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Monaco
authors.affiliation: Institute of Food Sciences, National Research Council (CNR-ISA), Via Roma 64, 83100, Avellino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Maurano
authors.affiliation: Institute of Food Sciences, National Research Council (CNR-ISA), Via Roma 64, 83100, Avellino, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Rossi
mesh_terms: D000818:Animals; D002446:Celiac Disease / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005903:Gliadin / Q000009:adverse effects*; D007213:Indomethacin / Q000009:adverse effects; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage*; D051379:Mice; D008822:Mice, Transgenic; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D044243:Linoleic Acids, Conjugated; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; C503589:cis-9, trans-11-conjugated linoleic acid; D005903:Gliadin; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D010447:Peptide Hydrolases; C038220:acylaminoacyl-peptidase; D007213:Indomethacin
keywords: Adaptive response; Celiac disease; Conjugated linoleic acid; Fatty acids; Gliadin; Nrf2
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