Pharmacological modification of oxygen affinity improves deformability of deoxygenated sickle erythrocytes: a possible therapeutic approach to sickle cell disease

Clin Sci (Lond). 1989 Apr;76(4):357-62. doi: 10.1042/cs0760357.

Abstract

1. The formation of polymerized haemoglobin S in sickle cells is critically dependent on the concentration of deoxygenated haemoglobin so that compounds which increase the oxygen affinity of haemoglobin S are potential anti-sickling agents. 2. BW12C [5-(2-formyl-3-hydroxyphenoxy)pentanoic acid] and BWA589C [4-(2-formyl-3-hydroxyphenoxymethyl)benzoic acid] are aromatic benzaldehydes that cause a dose-dependent left-shift of the oxygen saturation curve of haemoglobin S by stabilization of its oxy-(R)-conformation. 3. A 5 micron pore filtration method, which is highly sensitive to polymerization of haemoglobin S, was used to demonstrate a significant improvement in the deformability of deoxygenated sickle erythrocytes at concentrations (0.75-1.5 mmol/l] of BW12C and BWA589C that are achievable in vivo. Both compounds may therefore be of value for the treatment of sickle cell disease. 4. Filtration of sickle cells through pores of 5 microns diameter is a sensitive technique for evaluating the rheological effects of potential anti-sickling compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / metabolism
  • Anemia, Sickle Cell / therapy*
  • Benzaldehydes / pharmacology*
  • Benzoates / pharmacology*
  • Erythrocyte Deformability / drug effects*
  • Hemoglobin, Sickle
  • Humans
  • Oxygen / metabolism*

Substances

  • Benzaldehydes
  • Benzoates
  • Hemoglobin, Sickle
  • 5-(2-formyl-3-hydroxyphenoxy)pentanoic acid
  • tucaresol
  • Oxygen