TIME-RESOLVED ABSORPTION STUDY OF THE REACTION OF HYDROXYUREA WITH SICKLE-CELL HEMOGLOBIN

Hydroxyurea has been mixed with hemoglobin S and the reaction was stud ied using electronic absorption spectroscopy as a function of time and wavelength. The rate of conversion of oxyhemoglobin S to other specie s was determined and the nature of the reaction products was studied, We also report the formation of methemoglobin (and other reaction prod ucts) when deoxyhemoglobin S is combined with hydroxyurea. The probabl e increase in the formation of methemoglobin, and other potential reac tion products such as nitric oxide-hemoglobin, in patients with sickle cell anemia who are taking hydroxyurea as a therapeutic drug is discu ssed in terms of the pathophysiology of the disease. It is proposed th at methemoglobin and possibly nitric oxide-hemoglobin formation may pa rtially explain beneficial effects observed in these patients before t heir levels of fetal hemoglobin have increased. (C) 1998 Elsevier Scie nce B.V.