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

• Published in: Haematologica (Roma) Vol. 89; no. 11; pp. 1287 - 1298
• Main Authors: de Franceschi, L, Turrini, F, Honczarenko, M, Ayi, K, Rivera, A, Fleming, MD, Law, T, Mannu, F, Kuypers, FA, Bast, A, van der Vijgh, WJ, Brugnara, C
• Format: Journal Article
• Language: English
• Published: Pavia Haematologica 01.11.2004
• Subjects: Anemias. Hemoglobinopathies; Animals; Annexins - blood; Antioxidants - metabolism; Antioxidants - therapeutic use; beta-Thalassemia - blood; beta-Thalassemia - drug therapy; beta-Thalassemia - pathology; Biological and medical sciences; Chlorides - blood; Disease Models, Animal; Diseases of red blood cells; Erythrocyte Membrane - metabolism; Erythrocytes - drug effects; Erythrocytes - metabolism; Female; Hematologic and hematopoietic diseases; Hydroxyethylrutoside - analogs & derivatives; Hydroxyethylrutoside - blood; Hydroxyethylrutoside - therapeutic use; Immunoglobulin G - blood; Ion Transport; Male; Medical sciences; Mice; Oxidative Stress - drug effects; Potassium - blood; Vitamin E - blood; monoHER; Hemoglobinopathy; Animal model; Oxidative stress; Hematology; vitamin E; Red blood cell; Hemopathy; E-Vitamins; Genetic disease; erythrocyte; In vivo; Blood cell; K-Cl co-transport; Hemolytic anemia; β-Thalassemia; Transport; Phosphatidylserine
• ISSN: 0390-6078; 1592-8721

Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona, Verona, Italy. 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.