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Children with celiac disease have high levels of oxidative DNA damage
By Helen Albert
27 August 2010
Cancer Epidemiol Biomarkers Prev 2010; 19: 1960–1965

MedWire News: Children with celiac disease have higher than normal levels of the oxidative DNA damage biomarkers urinary 8-oxodG and 8-oxoGua, regardless of their diet, report researchers.

"Patients with celiac disease face increased risk of cancer and there is considerable circumstantial evidence that oxidatively damaged DNA may be used as a marker predictive of cancer development," explain Ryszard Olinski (Nicolaus Copernicus University, Bydgoszcz, Poland) and colleagues.

The researchers assessed levels of oxidative stress or oxidative DNA damage in 42 untreated and 75 treated (strict gluten-free diet) children with celiac disease with a mean age of 14.1 and 15.4 years, respectively. A group of 24 age-, gender-, and eating habit-matched controls were also included for comparison purposes.

The researchers measured urinary excretion of the biomarkers 8-oxodG and 8-oxoGua, as well as the level of oxidatively damaged DNA present in the leukocytes (8-oxodG).

Levels of leukocyte and urinary 8-oxodG and urinary 8-oxoGua were significantly higher in both treated and untreated celiac patients compared with controls.

In untreated and treated celiacs, and control children, mean levels of 8-oxodG in the urine were 2.48, 2.16, and 1.59 nmol/mmol of creatinine, respectively. Levels of urinary 8-oxoGua in the corresponding groups were 14.38, 11.66, and 7.78 nmol/mmol of creatinine.

Leukocyte levels of 8-oxodG in the same groups were 6.80, 6.16, and 4.39 per 106 unmodified dG.

Interestingly, treatment with a gluten-free diet did not seem to significantly reduce the concentration of 8-oxodG or 8-oxoGua, which suggests that "although diet can be partially responsible for oxidative stress/oxidatively damaged DNA in celiac patients, there is a factor independent of diet," write the authors.

"We recently showed that oxidatively damaged DNA is inversely correlated with the endogenous level of antioxidant vitamins and that vitamin A has the strongest effect of all antioxidant components on the damage," say Olinski et al.

They found that the untreated celiac children in the study had significantly lower levels of vitamin A and E (between group difference of 0.31 and 3.76 µmol/l, respectively) than the treated celiac children, suggesting that consumption of a gluten-free diet does at least partially ameliorate oxidative damage in these individuals.

The results of this study are published in the journal Cancer Epidemiology, Biomarkers and Prevention.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Comments
At 18:08 on 27/08/2010 Duncan Crow wrote
Symptoms can be reversed also with glutathioone precursors; we've been using undenatured whey and selenium, following other research. Glutathione is the master antioxidant and it regenerates other antioxidants.

This in addition to a low-carb "anti-candida" diet which reduces total gliadin.

Note that antioxidant malabsorption mentioned in the reference is not an issue with undenatured whey, which is absorbed without digestion even by an inflamed bowel.


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Free Radic Res. 1998 Jul;29(1):17-24.

Oxidative stress in subjects affected by celiac disease.
Odetti P, Valentini S, Aragno I, Garibaldi S, Pronzato MA, Rolandi E, Barreca T.

Department of Internal Medicine, University of Genoa, Italy. odetti@unige.it

Abstract
In order to study the role of oxidative stress in celiac disease, protein carbonyl groups, thiobarbituric acid-reactive substance and pentosidine were evaluated in the plasma of nine patients with asymptomatic celiac disease and in a control group (n = 25). Plasma alpha-tocopherol, retinol and lipids were determined in the same samples. The levels of markers of oxidative stress derived from both protein (carbonyl groups) and lipids (thiobarbituric acid-reactive substances) were significantly higher in celiac disease patients, whereas lipoproteins and alpha-tocopherol were significantly lower. These data indicate that in celiac disease, even when asymptomatic, a redox imbalance persists; this is probably caused by an absorption deficiency, even if slight. Dietary supplementation with antioxidant molecules may offer some benefit and deserves further investigation.

PMID: 9733018 [PubMed - indexed for MEDLINE]
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Lysosomal accumulation of gliadin p31-43 peptide induces oxidative stress and tissue transglutaminase-mediated PPARgamma downregulation in intestinal epithelial cells and coeliac mucosa.

Luciani A, Villella VR, Vasaturo A, Giardino I, Pettoello-Mantovani M, Guido S, Cexus ON, Peake N, Londei M, Quaratino S, Maiuri L.

Gut. 2010 Mar;59(3):311-9. Epub 2009 Dec 1. Erratum in: Gut. 2010 Jul;59(7):1007.
PMID: 19951908 [PubMed - indexed for MEDLINE]
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Antioxidant enzymes, glutathione and lipid peroxidation in peripheral blood of children affected by coeliac disease.

Stojiljkovic V, Todorovic A, Radlovic N, Pejic S, Mladenovic M, Kasapovic J, Pajovic SB.

Ann Clin Biochem. 2007 Nov;44(Pt 6):537-43.
PMID: 17961308 [PubMed - indexed for MEDLINE]
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