BioFactors 32 (2008) 161–167 161 IOS Press Coenzyme Q 10 and oxidative imbalance in Down syndrome: Biochemical and clinical aspects L. Tiano a,∗ , L. Padella b , P. Carnevali b , O. Gabrielli b , F. Bruge a , F. Principi a and G.P. Littarru a a Institute of Biochemistry, Polytechnic University of the Marche, Ancona, Italy b Pediatric Clinic Laboratory, Children Hospital Salesi, Polytechnic University of Marche, Ancona Abstract. Down syndrome (DS) is a chromosomal abnormality (trisomy 21) associated with mental retardation and Alzheimer- like dementia, characteristic change of the individual’s phenotype and premature ageing. Oxidative stress is known to play a major role in this pathology since a gene dose effect leads to elevated ratio of superoxide dismutase to catalase/glutathione peroxidase compared to controls in all age categories suggesting that oxidative imbalance contributes to the clinical manifestation of DS. Hyperuricemia is another feature of DS that has an interesting relationship with oxidative stress since uric acid represents an important free radical scavenger. However its formation is connected to the conversion of Xanthine dehydrogenase (XDH) to Xanthine oxidase (XO) which leads to concomitant production of free radicals. Here we report that plasma samples from DS patients in pediatric age, despite an increased total antioxidant capacity, largely due to elevated Uric acid content (UA), present significantly elevated markers of oxidative damage such as increased allantoin levels. Moreover DS plasma samples do not differ from healthy control ones in terms of Coenzyme Q10 and susceptibility to peroxidative stimuli. On the contrary, lymphocyte and platelet CoQ10 content was significantly lower in DS patients, a fact that might underlie oxidative imbalance at a cellular level. 1. Introduction DS is one of the most common genetic disorders associated with the trisomy of the entire or fractions of chromosome 21, the smallest human chromosome. The limited size and gene density are probably the main reasons underlying the compatibility of this aneuploidy with a high survival rate. The DS phenotype is characterized by a high variability leading to remarkable differences in penetrance and expressivity that are difficult to explain simply on the base of traditional gene-dosage hypothesis of genes located on chromosome 21. According to recent reviews there seems to be a general agreement on the fact that DS is better described as a multifactorial disease characterized by an amplified chromosomal instability arising not only from genetic but also environmental and stochastic influences that might explain the high variability in the manifestations of the clinical features [13]. In this view abnormal expression of trisomic genes, in association with responses to environmental stimuli might alter the expression of disomic genes as well. A pivotal role in these processes is played by reactive oxygen species both in relation to the acknowledged condition of oxidative stress experienced by DS [9,16,18] patients and to their activity as mediators of gene expression [17]. * Address for correspondence: Dr. Luca Tiano, Institute of Biochemisty, Polytechnic University of the Marche, Via Ranieri, 60100 Ancona, Italy. Tel.: +39 071 2204394; Fax: +39 071 2204398; E-mail: luca.tiano@unicam.it. 0951-6433/08/$17.00  2008 – IUBMB/IOS Press and the authors. All rights reserved