Gliadin and antioxidants

[Guest guest]

I found this very interesting ... gliadin seems to promote free radicals

-- maybe that is why we need so much Vit C on the Western diet ...

-- Heidi

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http://maelstrom.stjohns.edu/CGI/wa.exe?A2=ind0306d & L=celiac & O=D & P=9294

Selenium and CD - Introduction, Part 1, Part 2

2 Aug 2003

http://maelstrom.stjohns.edu/CGI/wa.exe?A2=ind0308a & L=celiac & O=D & P=5736

http://maelstrom.stjohns.edu/CGI/wa.exe?A2=ind0308a & L=celiac & O=D & P=5850

http://maelstrom.stjohns.edu/CGI/wa.exe?A2=ind0308a & L=celiac & O=D & P=5960

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The following 2 abstracts suggest that free radical production promoted by

gliadin may be involved in the process of gluten-intolerance. Even in

NORMAL blood serum, gliadin promotes IgE, IgG and free radicals. Could

these free radicals be the trigger of celiac disease (CD)? Could

antioxidant therapy or supplementation prevent CD from being triggered in

individuals not yet showing CD symptoms? Can antioxidants reduce CD

symptoms and prevent other food allergies from occuring in CD patients?

These are intriguing questions, and neither medical science nor I have the

answers at this time.

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Cytokine. 2003 Mar 21;21(6):270-80.

Wheat gliadin promotes the interleukin-4-induced IgE production by normal

human peripheral mononuclear cells through a redox-dependent mechanism.

Dugas B, Dugas N, Conti M, Calenda A, Pino P, Y, Mazier D,

Vouldoukis I.

Isocell Nutra SAS, 53 bd du General Martial Valion, 75015 Paris, France.

bdugas@...

Increased levels of serum IgE have been described in gliadin-intolerant

patients; however, biological mechanisms implicated in this immunoglobulin

production remained unknown. In this study, we demonstrated that in vitro

crude gliadins and gliadin lysates (Glilys) promoted the IL-4-induced IgE

production by human peripheral blood mononuclear cells (PBMC), indicating

that the biological process related to gliadin intolerance and/or allergy

may lead to IgE production in vivo. It was found that crude gliadin and

Glilys potentiated, after 13 days of culture in a dose-dependent manner, IL-

4-induced IgE production and, to a lesser extent, the IgG production, while

they did not affect IgA or IgM productions. This promoting effect of

gliadin and Glilys on the IL-4-induced activation of normal human PBMC was

also observed on the early release (2 days) of the soluble fraction of

CD23, suggesting its possible involvement in IgE potentiation. The

promoting effect of crude gliadin and Glilys appeared to be indirect

because they did not modify purified B-lymphocytes IgE production after IL-

4 and anti-CD40 monoclonal antibody stimulation.In addition, as revealed by

luminol-dependent chemiluminescence, we demonstrated that crude gliadin and

Glilys promoted a substantial production of free radicals by normal human

PBMC, treated or not with IL-4. This redox imbalance associated with an

increased IgE production led us to evaluate the effect of pharmacological

antioxidants (N-acetyl-cysteine (NAC) and Cu/Zn-superoxide dismutase

(SOD1)) on IgE production by human PBMC. The NAC and the intracellularly

delivered SOD1 were found to suppress the IL-4+/-crude gliadin or Glilys-

induced IgE production by normal human PBMC. Taken together, these data

indicated that gliadin specifically enhanced IL-4-induced IgE production by

normal human PBMC, probably by the regulation of redox pathways, and that

this 'pro-allergenic' effect could be counteracted by natural antioxidants:

thiols and/or vectorized SOD1.

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Biochim Biophys Acta. 1999 Jan 6;1453(1):152-60.

In vitro cytotoxic effect of wheat gliadin-derived peptides on the Caco-2

intestinal cell line is associated with intracellular oxidative imbalance:

implications for coeliac disease.

Rivabene R, Mancini E, De Vincenzi M.

Laboratory of Metabolism and Pathological Biochemistry, Istituto Superiore

di Sanita, Rome, Italy. mbpsegr@...

Coeliac disease (CD) is an inflammatory disorder of the upper small

intestine in which gluten acts as an essential factor in its pathogenesis.

Although it is generally accepted that cereal protein activation of the

immune system is involved in CD progression, a non-immunomediated cytotoxic

activity of gliadin-derived peptides on the jejunal/duodenal tract cannot

be excluded. In this work, considering that (a) little has been reported

about the intracellular metabolic events associated with gliadin toxicity,

and ( an important role for free radicals in a number of gastrointestinal

disease has been demonstrated, we investigated the in vitro effects of

gliadin-derived peptides on redox metabolism of Caco-2 intestinal cells

during a kinetic study in which cells were exposed to peptic-tryptic digest

of bread wheat up to 48 h. We found that the antiproliferative effects

displayed by gliadin exposure was associated with intracellular oxidative

imbalance, characterised by an increased presence of lipid peroxides, an

augmented oxidised (GSSG)/reduced (GSH) glutathione ratio and a loss in

protein-bound sulfhydryl groups. Significant structural perturbations of

the cell plasma membrane were also detected. Additional experiments

performed by using the specific GSH-depleting agent buthionine sulfoximine

provide evidence that the extent of gliadin-induced cell growth arrest

critically depends upon the 'basal' redox profile of the enterocytes. On

the whole, these findings seem to suggest that, besides the adoption of a

strictly gluten-free diet, the possibility for an adjuvant therapy with

antioxidants may be considered for CD patients.

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