The Efficacy of Reducing Agents or Antioxidants in Blocking the
Formation of Dense Cells and Irreversibly Sickled Cells In Vitro
Xunda A. Gibson,
Archil Shartava,
Jonah McIntyre,
Carlos A. Monteiro,
Yalin Zhang,
Arvind Shah,
Naomi F. Campbell, and
Steven
R. Goodman
From the Departments of Structural and Cellular Biology, Mathematics
and Statistics, Chemistry, and USA Comprehensive Sickle Cell Center,
University of South Alabama College of Medicine, Mobile, AL.
We show that N-acetylcysteine (NAC) has the ability to cause
statistically significant diminishment in the in vitro formation of
irreversibly sickled cells (ISCs) at concentrations greater than 250 µmol/L. Other antioxidants, approved for human use (cysteamine, succimer, dimercaprol), were not efficacious. NAC had the ability to
cause statistically significant conversion of ISCs formed in vivo back
to the biconcave shape. NAC was also shown to reduce the formation of
dense cells and increase the available thiols in 
-actin. We showed
that diminishing reduced glutathione (GSH), by treatment with
1-chloro-2,4-dinitrobenzene, resulted in increased dense cells. We
conclude the NAC blocks dense cell formation and ISC formation by
targeting channels involved in cellular dehydration and -actin,
respectively. The efficacy of NAC is probably due to its combined
antioxidant activity and ability to increase intracellular GSH.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4373-4378
© 1998 by The American Society of Hematology.
