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Physiologic and rheologic effects of the antisickling agent ethacrynic acid and its N-butylated derivative on normal and sickle erythrocytes.

Abstract
Ethacrynic acid, a loop diuretic, has been shown to inhibit hemoglobin S polymerization. Until now, however, most studies were performed using purified solutions of hemoglobin S. The experiments reported here were designed to examine the effects of ethacrynic acid and its n-butryic acid derivative on the rheological and physiological properties of intact red blood cells. Using net and unidirectional flux measurements, both agents were shown to cause ion and water loss from normal and sickle erythrocytes. Since cell shrinkage adversely influences red cell rheology, it is unlikely that this class of compounds, despite its ability to inhibit hemoglobin S polymerization, will prove useful in the treatment of sickle cell disease.
AuthorsE P Orringer, D S Blythe, J A Whitney, S Brockenbrough, D J Abraham
JournalAmerican journal of hematology (Am J Hematol) Vol. 39 Issue 1 Pg. 39-44 (Jan 1992) ISSN: 0361-8609 [Print] United States
PMID1536139 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antisickling Agents
  • Hemoglobin, Sickle
  • Polymers
  • Ethacrynic Acid
Topics
  • Anemia, Sickle Cell (blood)
  • Antisickling Agents (adverse effects, pharmacology)
  • Erythrocyte Membrane (drug effects, ultrastructure)
  • Erythrocytes (drug effects, physiology, ultrastructure)
  • Erythrocytes, Abnormal (drug effects, physiology, ultrastructure)
  • Ethacrynic Acid (adverse effects, pharmacology)
  • Hemoglobin, Sickle (metabolism)
  • Humans
  • Polymers
  • Rheology
  • Water-Electrolyte Balance (drug effects)

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