title: In vivo reduction of erythrocyte oxidant stress in a murine model of beta-thalassemia.
abstract: OBJECTIVE
  Oxidant damage is an important contributor to the premature destruction of erythrocytes and anemia in thalassemias. To assess the extent of oxidant damage of circulating erythrocytes and the effects of antioxidant therapy on erythrocyte characteristics and anemia, we used a mouse model of human beta-thalassemia intermedia (b1/b2 deletion).
  
  
  METHODS
  Several parameters indicative of oxidant damage were measured at baseline and following administration of the semi-synthetic flavonoid antioxidant, 7-monohydroxyethylrutoside (monoHER), to beta-thalassemic mice at a dose of either 500 mg/kg i.p. once a day (n=6) or 250 mg/kg i.p. twice a day (n=6) for 21 days.
  
  
  RESULTS
  Significant erythrocyte oxidant damage at baseline was indicated by: (i) dehydration, reduced cell K content, and up-regulated K-Cl co-transport; (ii) marked membrane externalization of phosphatidylserine; (iii) reduced plasma and membrane content of vitamin E; and (iv) increased membrane bound IgG. MonoHER treatment increased erythrocyte K content, and markedly improved all cellular indicators of oxidant stress and of lipid membrane peroxidation. While anemia did not improve, monoHER therapy reduced reticulocyte counts, improved survival of a fraction of red cells, and reduced ineffective erythropoiesis with decreased total bilirubin, lactate dehydrogenase and plasma iron.
  
  
  CONCLUSIONS
  Antioxidant therapy reverses several indicators of oxidant damage in vivo. These promising antioxidant effects of monoHER should be investigated further.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona, Verona, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: de Franceschi
authors.forename: Franco
authors.initials: F
authors.lastname: Turrini
authors.forename: Marek
authors.initials: M
authors.lastname: Honczarenko
authors.forename: Kojio
authors.initials: K
authors.lastname: Ayi
authors.forename: Alicia
authors.initials: A
authors.lastname: Rivera
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fleming
authors.forename: Terry
authors.initials: T
authors.lastname: Law
authors.forename: Franca
authors.initials: F
authors.lastname: Mannu
authors.forename: Frans A
authors.initials: FA
authors.lastname: Kuypers
authors.forename: Aalt
authors.initials: A
authors.lastname: Bast
authors.forename: Wim J F
authors.initials: WJ
authors.lastname: van der Vijgh
authors.forename: Carlo
authors.initials: C
authors.lastname: Brugnara
mesh_terms: D000818:Animals; D017302:Annexins / Q000097:blood; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D002712:Chlorides / Q000097:blood; D004195:Disease Models, Animal; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000097:blood; D017136:Ion Transport; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D011188:Potassium / Q000097:blood; D014810:Vitamin E / Q000097:blood; D017086:beta-Thalassemia / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology
chemical_list: D017302:Annexins; D000975:Antioxidants; D002712:Chlorides; D006896:Hydroxyethylrutoside; D007074:Immunoglobulin G; D014810:Vitamin E; D011188:Potassium