In vivo reduction of erythrocyte oxidant stress in a murine model of beta-thalassemia

L. de Franceschi, F. Turrini, M. Honczarenko, K. Ayi, A. Rivera, M.D. Fleming, T. Law, F. Mannu, F.A. Kuypers, A. Bast, W.J.F. van der Vijgh, C. Brugnara

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Abstract

BACKGROUND AND OBJECTIVES: 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). DESIGN AND 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. INTERPRETATION AND CONCLUSIONS: Antioxidant therapy reverses several indicators of oxidant damage in vivo. These promising antioxidant effects of monoHER should be investigated further.
Original languageEnglish
Pages (from-to)1287-1298
JournalHaematologica-the Hematology Journal
Volume89
Issue number11
Publication statusPublished - 1 Jan 2004

Cite this

de Franceschi, L., Turrini, F., Honczarenko, M., Ayi, K., Rivera, A., Fleming, M. D., Law, T., Mannu, F., Kuypers, F. A., Bast, A., van der Vijgh, W. J. F., & Brugnara, C. (2004). In vivo reduction of erythrocyte oxidant stress in a murine model of beta-thalassemia. Haematologica-the Hematology Journal, 89(11), 1287-1298. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15531450