Combination Therapy of Erythropoietin , Hydroxyurea , and Clotrimazole in a p Thalassemic Mouse : A Model for Human Therapy

p thalassemia (p thal) in DBA/2J mice is a consequence of the spontaneous and complete deletion of the p major globin gene. Homozygous p thal mice have clinical and biological features similar t o those observed in human p thal intermedia. Erythrocytes in human p thal are characterized by a relative cell dehydration and reduced K+ content. The role of this erythrocyte dehydration in the reduced erythrocyte survival, which typifies the disease, has not previously been evaluated. We examined for 1 month the effects on the anemia and the erythrocyte characteristics of p thal mice of daily treatment with either clotrimazole (CLT), an inhibitor of red blood cell (RBC) dehydration via the Gardos channel, or human recombinant erythropoietin (r-HuEPO), or hydroxyurea (HU). The use of either r-HuEPO or HU induced a significant increase in hemoglobin (Hb), hematocrit (Hct), erythrocyte K’ and a decrease in percent reticulocytes, sug-