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Adaptive response activated by dietary cis9, trans11 conjugated linoleic acid prevents distinct signs of gliadin-induced enteropathy in mice

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European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

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.

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Abbreviations

AI:

Albumin/globulin and indomethacin treatment

APEH:

Acylpeptide hydrolase

CD:

Celiac disease

CT-like:

Chymotrypsin-like activity of proteasome

CLA:

Conjugated linoleic acid

c9:

cis9, trans11-CLA isomer

t10:

trans10, cis12-CLA isomer

DQ8:

HLA-DQ8-transgenic mice

GCL:

γ-Glutamate cysteine ligase

GCs:

Goblet cells

GI:

Gliadin and indomethacin treatment

GSH:

Reduced glutathione

GSHtot :

Total thiols

GSSG:

Glutathione disulfide

GST:

Glutathione-S transferase

GSR:

Glutathione-S reductase

HO1:

Heme oxygenase-1

Nrf2:

Nuclear factor-E2-related factor-2

NQO1:

NAD(P)H: quinone oxidoreductase

PC:

Protein bound carbonyls

ROS:

Reactive oxygen species

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Acknowledgments

The authors wish to thank Sandro Festa for his valuable help in improving the English language of the manuscript.

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    Authors and Affiliations

    1. Institute of Food Sciences, National Research Council (CNR-ISA), Via Roma 64, 83100, Avellino, Italy

      Paolo Bergamo, Francesco Maurano & Mauro Rossi

    2. Institute of Biosciences and Bioresources, National Research Council (CNR-IBBR), Naples, Italy

      Gianna Palmieri, Ennio Cocca & Marta Gogliettino

    3. Department of Biology, University “Federico II” of Naples, Naples, Italy

      Ida Ferrandino & Antonio Monaco

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    1. Paolo Bergamo
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    Correspondence to Paolo Bergamo.

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    Gianna Palmieri, Ennio Cocca and Ida Ferrandino have contributed equally to this work.

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    Bergamo, P., Palmieri, G., Cocca, E. et al. Adaptive response activated by dietary cis9, trans11 conjugated linoleic acid prevents distinct signs of gliadin-induced enteropathy in mice. Eur J Nutr 55, 729–740 (2016). https://doi.org/10.1007/s00394-015-0893-2

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