Substituted benzaldehydes (12C79 and 589C80) that stabilize oxyhaemoglobin also protect sickle cells against calcium-mediated dehydration.
Reversibly sickled cells from patients with homozygous sickle-cell disease were prepared by Percoll-Isopaque density gradient separation and subjected to 15 h of cyclical deoxygenation-reoxygenation in the presence of Ca. After 15 h the sickle cells became dehydrated, losing volume secondary to K efflux via the Ca-activated (Gardos) channel, and showed impaired filterability through 5 microns diameter pores. The substituted benzaldehydes 12C79 and 589C80, which stabilize the oxy-conformation of sickle haemoglobin, showed an additional protective effect at pharmacological concentration by maintaining the K concentration, mean cell volume, and deformability of sickle cells. Drugs that increase the oxygen affinity of sickle haemoglobin may be more effective than specific inhibitors of Ca entry or K efflux in preserving the cation homeostasis and deformability of sickle cells during sickling in vivo.
Stone
P C
PC
Department of Haematology, Medical School, University of Birmingham.
Nash
G B
GB
Stuart
J
J
D000755:Anemia, Sickle Cell / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D000986:Antisickling Agents / Q000494:pharmacology*; D001547:Benzaldehydes / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D003681:Dehydration / Q000097:blood* / Q000378:metabolism / Q000517:prevention & control; D004913:Erythrocytes, Abnormal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D010108:Oxyhemoglobins / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000032:analysis / Q000378:metabolism
D000986:Antisickling Agents; D001547:Benzaldehydes; D001565:Benzoates; D010108:Oxyhemoglobins; C039599:5-(2-formyl-3-hydroxyphenoxy)pentanoic acid; C059629:tucaresol; D011188:Potassium; D002118:Calcium