title: Evaluation of urinary biomarkers of oxidative/nitrosative stress in children with Down syndrome.
abstract: OBJECTIVE
  It has been suggested that oxidative stress plays a key role in the pathogenesis of Down syndrome (DS). However, urinary biomarkers of oxidative stress have been little studied in this condition. Thus, we aimed to assess a set of urinary oxidative/nitrosative stress biomarkers in children with DS, with and without hypothyroidism, which comprise: 8-hydroxy-2'-deoxyguanosine (8-OHdG), isoprostane 15-F(2t)-IsoP, thiobarbituric acid-reacting substances (TBARS), advanced glycation end products (AGEs), dityrosine (diTyr), hydrogen peroxide (H(2)O(2)) and nitrite/nitrate (NOx).
  
  
  METHODS
  Fluorimetric and spectrophotometric assays were performed in children with DS (n=26), some of them taking levothyroxine for hypothyroidism (n=7), and their non-Down siblings (n=19).
  
  
  RESULTS
  We found that only levels of diTyr were increased in DS, although no differences were obtained when hypothyroid DS children were excluded. Levels of 8-OHdG, 15-F(2t)-IsoP, TBARS, AGEs, H(2)O(2) and NOx did not differ neither between DS and controls nor between hypothyroid DS children and DS without hypothyroidism diagnosed. However, diTyr is increased in hypothyroid DS children compared with controls. Negative correlations with age were obtained for 8-OHdG, diTyr and NOx in DS and controls and for 8-OHdG, 15-F(2t)-IsoP, TBARS and AGEs in DS.
  
  
  CONCLUSIONS
  Increased oxidative stress in children with DS cannot be explained by the urinary levels of 8-OHdG, 15-F(2t)-IsoP, TBARS, AGEs, diTyr, H(2)O(2) and NOx, at least with the assays used. Nonetheless, urinary diTyr could be used as oxidative/nitrosative stress biomarker in hypothyroid DS children. The present work presents evidence of a probable renal impairment in children with DS receiving levothyroxine for hypothyroidism.
authors.affiliation: Department of Cellular and Molecular Medicine, Centre for Biological Research — Spanish National Research Council (CIB-CSIC), Madrid, Spain. ccampos@cib.csic.es
authors.forename: Carlos
authors.initials: C
authors.lastname: Campos
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Guzmán
authors.forename: Encarnación
authors.initials: E
authors.lastname: López-Fernández
authors.forename: Angela
authors.initials: A
authors.lastname: Casado
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004314:Down Syndrome / Q000652:urine*; D005260:Female; D017127:Glycation End Products, Advanced / Q000652:urine; D006801:Humans; D006861:Hydrogen Peroxide / Q000652:urine; D007037:Hypothyroidism / Q000652:urine*; D015227:Lipid Peroxidation; D008297:Male; D009566:Nitrates / Q000652:urine*; D009573:Nitrites / Q000652:urine*; D018384:Oxidative Stress; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D009566:Nitrates; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; C075750:8-epi-prostaglandin F2alpha; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015237:Dinoprost; D006861:Hydrogen Peroxide; C007543:dityrosine; D003849:Deoxyguanosine