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Multiple evidence for an early age pro-oxidant state in Down Syndrome patients

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Abstract

Oxidative stress has been associated with Down syndrome (DS) and with its major phenotypic features, such as early ageing. In order to evaluate an in vivo pro-oxidant state, the following analytes were measured in a group of DS patients aged 2 months to 57 years: (a) leukocyte 8-hydroxy-2′-deoxyguanosine (8-OHdG); (b) blood glutathione; (c) plasma levels of: glyoxal (Glx) and methylglyoxal (MGlx); some antioxidants (uric acid, UA, ascorbic acid, AA and Vitamin E), and xanthine oxidase (XO) activity. A significant 1.5-fold increase in 8-OHdG levels was observed in 28 DS patients vs. 63 controls, with a sharper increase in DS patients aged up to 30 years. The GSSG:GSH×100 ratio was significantly higher in young DS patients (< 15 years), in contrast to DS patients aged ≥15 years that showed a significant decrease in the GSSG:GSH×100 ratio ratio vs. controls of the respective age groups. Plasma Glx levels were significantly higher in young DS patients, whereas no significant difference was detected in DS patients aged ≥15 years. Unlike Glx, the plasma levels of MGlx were found to be significantly lower in DS patients vs. controls. A significant increase was observed in plasma levels of UA in DS patients that could be related to an increased plasma XO activity in DS patients. The plasma concentrations of AA were also increased in young (< 15 years) DS patients, but not in older patients vs. controls in the same age range. The levels of Vitamin E in DS patients did not differ from the values determined in control donors. The evidence for a multiple pro-oxidant state in young DS patients supports the role of oxidative stress in DS phenotype, with relevant distinctions according to patients’ ages.

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Abbreviations

AA:

ascorbic acid

DS:

Down syndrome

GSSG:

glutathione disulfide

GSH:

reduced glutathione

Glx:

glyoxal

MGlx:

methylglyoxal

8-OHdG:

8-hydroxy-2′-deoxyguanosine

SOD-1:

Cu,Zn superoxide dismutase

TG:

total glutathione

UA:

uric acid

XO:

xanthine oxidase

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Acknowledgements

This study was supported by the European Commission, DG XII, contract # BMH4-CT98–3107, and by the Italian Association for Fanconi Anaemia Research (AIRFA). The Italian Association of Down Persons (AIPD) provided valuable collaboration in contacting the patients’ families. Thanks are due to Professor Stefano Calvieri (La␣Sapienza University, Rome) for contributing to patient recruitment, and to Dr. Ingrid Žitňanová, Ph.D. (Comenius University, Bratislava) for critical evaluation of the manuscript. Samples were␣processed by Dr. Ebru E. Akişı ık, Ph.D., Mr.␣Paolo Ciavolino, Mrs. Germana De Stefano, and Mrs. Francesca Gallucci. The assistance of Mrs. Francesca Panzeri and Ms. Virginia Rossi in project organization and data processing is gratefully acknowledged.

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Pallardó, F.V., Degan, P., d’Ischia, M. et al. Multiple evidence for an early age pro-oxidant state in Down Syndrome patients. Biogerontology 7, 211–220 (2006). https://doi.org/10.1007/s10522-006-9002-5

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