Substituted benzaldehydes (12C79 and 589C80) that stabilize oxyhaemoglobin also protect sickle cells against calcium-mediated dehydration

Br J Haematol. 1992 Jul;81(3):419-23. doi: 10.1111/j.1365-2141.1992.tb08250.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Sickle Cell / blood*
  • Anemia, Sickle Cell / metabolism
  • Anemia, Sickle Cell / pathology
  • Antisickling Agents / pharmacology*
  • Benzaldehydes / pharmacology*
  • Benzoates / pharmacology*
  • Calcium / pharmacology*
  • Dehydration / blood*
  • Dehydration / metabolism
  • Dehydration / prevention & control
  • Erythrocytes, Abnormal / drug effects
  • Erythrocytes, Abnormal / metabolism
  • Erythrocytes, Abnormal / pathology*
  • Humans
  • Oxyhemoglobins / drug effects
  • Oxyhemoglobins / metabolism*
  • Potassium / analysis
  • Potassium / metabolism

Substances

  • Antisickling Agents
  • Benzaldehydes
  • Benzoates
  • Oxyhemoglobins
  • 5-(2-formyl-3-hydroxyphenoxy)pentanoic acid
  • tucaresol
  • Potassium
  • Calcium