Time resolved absorption study of the reaction of hydroxyurea with sickle cell hemoglobin.
Hydroxyurea has been mixed with hemoglobin S and the reaction was studied using electronic absorption spectroscopy as a function of time and wavelength. The rate of conversion of oxyhemoglobin S to other species was determined and the nature of the reaction products was studied. We also report the formation of methemoglobin (and other reaction products) when deoxyhemoglobin S is combined with hydroxyurea. The probable increase in the formation of methemoglobin, and other potential reaction products such as nitric oxide-hemoglobin, in patients with sickle cell anemia who are taking hydroxyurea as a therapeutic drug is discussed in terms of the pathophysiology of the disease. It is proposed that methemoglobin and possibly nitric oxide-hemoglobin formation may partially explain beneficial effects observed in these patients before their levels of fetal hemoglobin have increased.
Kim-Shapiro
D B
DB
Department of Physics, Wake Forest University, Winston-Salem, NC 27109-7507, USA. shapiro@wfu.edu
King
S B
SB
Bonifant
C L
CL
Kolibash
C P
CP
Ballas
S K
SK
D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy; D000986:Antisickling Agents / Q000494:pharmacology*; D006420:Hemeproteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006451:Hemoglobin, Sickle / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D066298:In Vitro Techniques; D008706:Methemoglobin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010108:Oxyhemoglobins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013053:Spectrophotometry
D000986:Antisickling Agents; D006420:Hemeproteins; D006451:Hemoglobin, Sickle; D010108:Oxyhemoglobins; C038875:deoxyhemoglobin, sickle; C001332:hemichrome; C038876:methemoglobin, sickle; C029775:oxyhemoglobin S; D008706:Methemoglobin; D006918:Hydroxyurea