title: Morphological changes and oxidative damage in Rett Syndrome erythrocytes.
abstract: BACKGROUND
  Hypoxemia and increased oxidative stress (OS) have been reported in Rett Syndrome (RTT), a genetical neurodevelopmental disorder. Although OS and hypoxemia can lead to red blood cells (RBCs) shape abnormalities, no information on RBCs morphology in RTT exists. Here, RBCs shape was evaluated in RTT patients and healthy subjects as a function of OS markers, blood oxygenation, pulmonary gas exchange, and cardio-respiratory parameters.
  
  
  METHODS
  RBCs morphology was evaluated by Scanning Electron Microscopy. Intraerythrocyte and plasma non protein-bound iron (NPBI), esterified F(2)-Isoprostanes (F(2)-IsoPs), 4-HNE protein adducts (4-HNE PAs) were measured. Pulmonary oxygen gradients and PaO(2) were evaluated by gas analyzers and cardiopulmonary variables by pulse oximetry. In RTT patients these parameters were assessed before and after ω-3 polyunsaturated fatty acids (ω-3 PUFAs) administration.
  
  
  RESULTS
  Altered RBCs shapes (leptocytes) and increased NPBI were present in RTT, together with increased erythrocyte membrane esterified F(2)-IsoPs and 4-HNE PAs. Abnormal erythrocyte shapes were related to OS markers levels, pulmonary gas exchange, PaO(2) and cardio-respiratory variables. After ω-3 PUFAs, a decrease of leptocytes was accompanied by a progressive increase in reversible forms of RBCs. This partial RBCs morphology rescue was related to decreased OS damage markers, improved pulmonary oxygen exchange, and cardiopulmonary physiology.
  
  
  CONCLUSIONS
  These findings indicate that in RTT 1) RBCs shape is altered; 2) the OS-hypoxia diad is critical in generating altered RBCs shape and membrane damage; 3) ω-3 PUFAs are able to partially rescue RBCs morphology and the OS-derived damage.
  
  
  CONCLUSIONS
  RBCs morphology is an important biosensor for OS imbalance and chronic hypoxemia.
authors.affiliation: Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, Siena, Italy. lucia.ciccoli@unisi.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccoli
authors.forename: Claudio
authors.initials: C
authors.lastname: De Felice
authors.forename: Eugenio
authors.initials: E
authors.lastname: Paccagnini
authors.forename: Silvia
authors.initials: S
authors.lastname: Leoncini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pecorelli
authors.forename: Cinzia
authors.initials: C
authors.lastname: Signorini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Belmonte
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
authors.forename: Marcello
authors.initials: M
authors.lastname: Rossi
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015687:Cell Hypoxia; D048430:Cell Shape; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism*; D028441:F2-Isoprostanes / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D000860:Hypoxia; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen; D011659:Pulmonary Gas Exchange; D015518:Rett Syndrome / Q000097:blood* / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes; D015525:Fatty Acids, Omega-3; D005978:Glutathione; D010100:Oxygen