Inhibition of erythrocyte sickling in vitro by pyridoxal

Abstract

To test the antisickling activity of pyridoxal, we compared the oxygen affinity and the percent sickling at low PO2 of untreated erythrocytes with values for cells from the same blood sample incubated with pyridoxal, glyceraldehyde, or pyridoxine. Pyridoxal increased oxygen affinity much more than glyceraldehyde. 20 mM pyridoxal and glyceraldehyde had equivalent antisickling activity. At PO2 levels above 20 mm Hg, both agents reduced sickling to less than 2%. In samples examined by electron microscopy, pyridoxal reduced the percent sickled cells and the percent cells that contain hemoglobin S fibers by the same amount (from 74 to 3%). Pyridoxine had no effect on oxygen affinity or sockling. Pyridoxal reacts with intracellular hemoglobin to increase oxygen affinity, which inhibits hemoglobin S polymerization and sickling.