Arylamine-Induced Hemolytic Anemia: Electron Spin Resonance Spectrometry Studies

  • Timothy P. Bradshaw
  • D. C. McMillan
  • R. K. Crouch
  • D. J. Jollow
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)


A variety of arylamine derivatives (e.g. dapsone, primaquine) are known to produce hemolytic anemia in man and experimental animals. Extensive studies in the 1950’s and 60’s established that hemolytic drugs induced methemoglobinemia and loss of erythrocytic reduced glutathione (GSH), and that individuals deficient in erthrocytic glucose-6-phosphate dehydrog-enase displayed enhanced susceptibility to drug-induced hemolytic anemia (for review, see E. Beutler, 1969; E. Beutler, 1972). Since drugs such as primaquine were active in vivo but not in vitro, the concept arose that the drugs were metabolized in the liver to active/reactive metabolites which, on entry to the red cell, produced a state of “oxidative stress”. The resulting oxidative damage to critical sites within the red cell has been considered to lead to their “premature aging” and premature removal from the circulation by the spleen (A.R. Tarlov, et al., 1962; F.C. Gooden-Smith, et al., 1974; G. Cohen et al., 1964; A. Miller et al., 1970; R.W. Carrell, et al., 1975). The nature of the oxidant stress and the identity of the critical sites, however, are still unclear. Since the oxidation of hemoglobin to methemoglobin is known to be associated with the reduction of oxygen, much work has centered around the role of active oxygen species and free radicals as molecules capable of attacking cellular components (G. Cohen, et al., 1964; R.W. Carrell, et al., 1975; H.P. Misra et al., 1976; H.A. Itano, et al., 1977; B. Goldberg, et al., 1977). We have recently shown that phenylhydroxylamine (PHA) is a direct acting hemotoxin, capable of damaging the red blood cell during in vitro incubation such that, when readministered to isologous rats, the cells are rapidly sequestered by the spleen (J.H. Harrison, et al., 1986). This communication describes spin trap studies aimed at determination of whether or not free radical specie(s) are formed in the red cell in response to PHA, and if so, the identification of these specie(s).


Hemolytic Anemia Active Oxygen Species Critical Site Free Radical Species Thiyl Radical 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Beutler,E. (1969). Pharmacol. Reviews 21, 73.Google Scholar
  2. Beutler, E. (1972). In: The Metabolic Basis of Inherited Disease (J.B. Stanbury, J.B. Wyngaarden, and D.S. Fredrickson, eds.) McGraw Hill 3rd Edition, 1358–1388.Google Scholar
  3. Britigan, B.E., Cohen, M.S. and Rosen, G.M. (1987). J. Leuk. Biol. 41, 349.Google Scholar
  4. Buettner, G.R. (1987). Free Rad. Biol. Med. 3, 259.CrossRefPubMedGoogle Scholar
  5. Buettner, G.R. (1989). In: Handbook of Methods for Oxygen Radical Research (R.A. Greenwald, ed.) CRC Press, Cleveland, Ohio.Google Scholar
  6. Carrell, R.W., Winterbourn, C.C., Rachmilewitz, E.A. (1975). Brit. J. Haematol. 30, 259.CrossRefGoogle Scholar
  7. Cohen, G. and Hochstein, P. (1964). Biochemistry 3, 895.CrossRefPubMedGoogle Scholar
  8. Davies, M.J., forni, L.G. and Shuter, S.L. (1987). Chem.-Biol. Interactions 61, 177.CrossRefGoogle Scholar
  9. Goldberg, B. and Stern, A. (1977). Mol. Pharmacol. 13, 832.Google Scholar
  10. Gooden-Smith, F.C. and White, J.M. (1974). Brit. J. Haematol. 26, 573.Google Scholar
  11. Harrison, J.H. and Jollow, D.J. (1986). Pharmacol. Exp. Ther. 238, 1045.Google Scholar
  12. Harrison, J.H. and Jollow, D.J. (1986). Chromatogr. 277, 173.Google Scholar
  13. Itano, H.A., Hirota, K., and Vedvick, T.S. (1977). Proc. Nat. Acad. Sci. 74, 2556.CrossRefPubMedGoogle Scholar
  14. Miller, A. and Smith, H.C. (1970). Brit. J. Haematol. 19, 417.CrossRefGoogle Scholar
  15. Misra, H.P. and Fridovich, I. (1976). Biochemistry 15, 681.CrossRefPubMedGoogle Scholar
  16. Ross, D., Norbeck, K. and Moldeus, P.J. (1985). Biol. Chem. 260, 15028.Google Scholar
  17. Tarlov, A.R., Brewer, G.J., Carson, P.E., and Alving, A.S. (1962). Arch. internal Med 109, 137.CrossRefGoogle Scholar
  18. Thornalley, P.J. and Bannister, J.V. (1989). In: Handbook of Methods for Oxygen Radical Research (R.A. Greenwald, ed.) CRC Press, Cleveland, Ohio.Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Timothy P. Bradshaw
    • 1
  • D. C. McMillan
    • 1
  • R. K. Crouch
    • 1
  • D. J. Jollow
    • 1
  1. 1.Departments of Pharmacology and OphthamologyMedical University of South CarolinaCharlestonUSA

Personalised recommendations