THE EFFICACY OF REDUCING AGENTS OR ANTIOXIDANTS IN BLOCKING THE FORMATION OF DENSE CELLS AND IRREVERSIBLY SICKLED CELLS IN-VITRO

We show that N-acetylcysteine (NAC) has the ability to cause statistic ally significant diminishment in the in vitro formation of irreversibl y sickled cells (ISCs) at concentrations greater than 250 mu mol/L. Ot her antioxidants, approved for human use (cysteamine, succimer, dimerc aprol), were not efficacious. NAC had the ability to cause statistical ly 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 beta-actin. We showed that diminishin g reduced glutathione (GSH), by treatment with 1-chloro-2,4-dinitroben zene, resulted in increased dense cells. We conclude the NAC blocks de nse cell formation and ISC formation by targeting channels involved in cellular dehydration and beta-actin, respectively, The efficacy of NA C is probably due to its combined antioxidant activity and ability to increase intracellular GSH. (C) 1998 by The American Society of Hemato logy.