TY - JOUR
T1 - Conjugated linoleic acid protects against gliadin-induced depletion of intestinal defenses
AU - Bergamo, Paolo
AU - Gogliettino, Marta
AU - Palmieri, Gianna
AU - Cocca, Ennio
AU - Maurano, Francesco
AU - Stefanile, Rosita
AU - Balestrieri, Marco
AU - Mazzarella, Giuseppe
AU - David, Chella
AU - Rossi, Mauro
PY - 2011/9
Y1 - 2011/9
N2 - Scope: 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. Methods and 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. Conclusion: 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.
AB - Scope: 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. Methods and 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. Conclusion: 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.
KW - Conjugated linoleic acid
KW - Gluten toxicity
KW - Nrf2-mediated defenses
KW - Proteasome-acylpeptide hydrolase activity
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U2 - 10.1002/mnfr.201100295
DO - 10.1002/mnfr.201100295
M3 - Article
C2 - 21954188
AN - SCOPUS:80053263292
SN - 1613-4125
VL - 55
SP - S248-S256
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - SUPPL. 2
ER -