Biochemical Evaluation of the Effects of Hydroxyurea in Vitro on Red Blood Cells

Abstract

Hydroxyurea (HU) is a low-cost, low-toxicity drug that is often used in diseases, such as sickle cell anemia and different types of cancer. Its effects on the red blood cells (RBC) are still not fully understood. The in vitro effects of HU were evaluated on the biochemical parameters of the RBC from healthy individuals that were treated with 0.6 mM or 0.8 mM HU for 30 min and 1 h. After 30 min, there was a significant increase in almost all of the parameters analyzed in the two concentrations of HU, except for the pyruvate kinase (PK) activity. A treatment with 0.8 mM HU for 1 h resulted in a reduction of the levels of lipid peroxidation, Fe3+, and in the activities of some of the enzymes, such as glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), and PK. After the incubation for 1 h, the levels of H2O2, lipid peroxidation, reduced glutathione (GSH), enzymatic activity (hexokinase, G6PD, and superoxide dismutase (SOD) were reduced with the treatment of 0.8 mM HU when compared with 0.6 mM. The results have suggested that a treatment with HU at a concentration of 0.8 mM seemed to be more efficient in protecting against the free radicals, as well as in treating diseases, such as sickle cell anemia. HU appears to preferentially stimulate the pentose pathway over the glycolytic pathway. Although this study was carried out with the RBC from healthy individuals, the changes described in this study may help to elucidate the mechanisms of action of HU when administered for therapeutic purposes.

Keywords

• hydroxyurea
• red blood cells
• energy metabolism
• antioxidant system
• reactive oxygen species