MOLECULAR AND CELLULAR EFFECTS OF ANTISICKLING CONCENTRATIONS OF ALKYLUREAS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 48  (2) , 273-282
Abstract
Alkylureas are capable of inhibiting sickling in vitro and the gelation of solutions of Hb S at concentrations between 0.05 and 0.1 M with increasing effectiveness that is directly proportional to the length of the alkyl chain (butyl > propyl > ethyl > methyl). The inhibitory effect is independent of pH between 6.5 and 7.5 and is a process driven by entropy. The alkylureas at concentrations of 0.1 M have minimal effects on several erythrocyte functions. O2 equilibria, osmotic fragility, reduced glutathione content, and glutathione reductase activity are totally unaffected, while pyruvic kinase activity is decreased only by butylurea by about 20%, and G-6-P dehydrogenase activity is decreased progressively to a maximum of 30% in direct proportion to the length of the alkyl chain. Alkylureas not only inhibit sickling but are also capable of desickling erythrocytes that have been maintained in the deoxygenated state. They have little effect on several erythrocyte functions at antisickling concentrations, but their toxicity must be evaluated before they can be examined as potential therapeutic agents for the treatment or prevention of acute episodes in sickle cell anemia.