Volume 88, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Anti-malarial 8-aminoquinolines drugs cause acute hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDD). Efforts to develop non-hemolytic 8-aminoquinolines have been severely limited caused by the lack of a predictive animal model of hemolytic potential that would allow screening of candidate compounds. This report describes a G6PDD mouse model with a phenotype closely resembling the G6PDD phenotype found in the African A-type G6PDD human. These G6PDD mice, given different doses of primaquine, which used as a reference hemolytic drug, display a full array of hemolytic anemia parameters, consistently and reproducibly. The hemolytic and therapeutic indexes were generated for evaluation of hemotoxicity of drugs. This model demonstrated a complete hemolytic toxicity response to another known hemolytic antimalarial drug, pamaquine, but no response to non-hemolytic drugs, chloroquine and mefloquine. These results suggest that this model is suitable for evaluation of selected 8-AQ type candidate antimalarial drugs for their hemolytic potential.


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  1. Beutler E, , 1994. G6PD deficiency. Blood 84: 36133636. [Google Scholar]
  2. Beutler E, , 1996. G6PD: population genetics and clinical manifestations. Blood Rev 10: 4552.[Crossref] [Google Scholar]
  3. Beutler E, , 1959. The hemolytic effect of primaquine and related compounds: a review. Blood 14: 103139. [Google Scholar]
  4. Baird JK, Fryauff DJ, Basri H, Bangs MJ, Subianto B, Wiady I, Purnomo Leksana B, Masbar S, Richie TL, Jones TR, Tjitra E, Wignall ES, Hoffman SL, , 1995. Primaquine for prophylaxis against malaria among nonimmune transmigrants in Irian Jaya, Indonesia. Am J Trop Med Hyg 52: 479484. [Google Scholar]
  5. Baird JK, Fryauff DJ, Hoffman SL, , 2003. Primaquine for prevention of malaria in travelers. Clin Infect Dis 37: 16591667.[Crossref] [Google Scholar]
  6. Baird JK, Hoffman SL, , 2004. Primaquine therapy for malaria. Clin Infect Dis 39: 13361345.[Crossref] [Google Scholar]
  7. Baird JK, , 1998. Primaquine as anti-relapse therapy for Plasmodium vivax . Trans R Soc Trop Med Hyg 92: 687.[Crossref] [Google Scholar]
  8. Baird JK, Surjadjaja C, , 2011. Consideration of ethics in primaquine therapy against malaria transmission. Trends Parasitol 27: 1116.[Crossref] [Google Scholar]
  9. World Health Organization, 2006. Guidelines for the Treatment of Malaria. Second edition. Geneva: World Health Organization, 5258. [Google Scholar]
  10. Beutler E, , 1969. Drug-induced hemolytic anemia. Pharmacol Rev 21: 73103. [Google Scholar]
  11. Pretsch W, Charles DJ, Merkle S, , 1988. X-linked glucose-6-phosphate dehydrogenase deficiency in Mus musculus . Biochem Genet 26: 89103.[Crossref] [Google Scholar]
  12. Spolarics Z, Condon MR, Siddiqi M, Machiedo GW, Deitch EA, , 2004. Red blood cell dysfunction in septic glucose-6-phosphate dehydrogenase-deficient mice. Am J Physiol Heart Circ Physiol 286: H2118H2126.[Crossref] [Google Scholar]
  13. Wilmanski J, Siddiqi M, Deitch EA, Spolarics Z, , 2005. Augmented IL-10 production and redox-dependent signaling pathways in glucose-6-phosphate dehydrogenase-deficient mouse peritoneal macrophages. J Leukoc Biol 78: 8594.[Crossref] [Google Scholar]
  14. Spolarics Z, Siddiqi M, Siegel JH, Garcia ZC, Stein DS, Ong H, Livingston DH, Denny T, Deitch EA, , 2001. Increased incidence of sepsis and altered monocyte functions in severely injured type A- glucose-6-phosphate dehydrogenase-deficient African American trauma patients. Crit Care Med 29: 728736.[Crossref] [Google Scholar]
  15. Beutler E, Duparc S, G6PD Deficiency Working Group; , 2007. Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development. Am J Trop Med Hyg 77: 779789. [Google Scholar]
  16. Vale N, Moreira R, Gomes P, , 2009. Primaquine revisited six decades after its discovery. Eur J Med Chem 44: 937953.[Crossref] [Google Scholar]
  17. Johns JL, Shooshtari MP, Christopher MM, , 2008. Development of a technique for quantification of reticulocytes and assessment of erythrocyte regenerative capacity in birds. Am J Vet Res 69: 10671072.[Crossref] [Google Scholar]
  18. Nobes PR, Carter AB, , 1990. Reticulocyte counting using flow cytometry. J Clin Pathol 43: 675678.[Crossref] [Google Scholar]
  19. Summerfield M, Tudhope GR, , 1979. Spectrophotometric method applicable to in vitro studies of Heinz body formation in erythrocytes. Acta Haematol 61: 222225.[Crossref] [Google Scholar]
  20. Watanabe J, Grijalva V, Hama S, Barbour K, Berger F, Navab M, Fogelman A, Reddy S, , 2009. Hemoglobin and its scavenger protein haptoglobin associate with ApoA-1-containing particles and influence the inflammatory properties and function of high density lipoprotein. J Biol Chem 284: 1829218301.[Crossref] [Google Scholar]
  21. Neifer S, Jung A, Bienzle U, , 1991. Characterization of erythrocytic glucose-6-phosphate dehydrogenase in a mouse strain with reduced G6PD activity. Biomed Biochim Acta 50: 233238. [Google Scholar]
  22. Reagan-Shaw S, Nihal M, Ahmad N, , 2007. Dose translation from animal to human studies revisited. FASEB J 22: 659661.[Crossref] [Google Scholar]
  23. Alving AS, Johnson CF, Tarlov AR, Brewer GJ, Kellrmeyer RW, Carson PE, , 1960. Mitigation of the hemolytic effect of primaquine and enhancement of its action against exoerythrocytic forms of the Chesson strain of Plasmodium vivax by intermittent regimens of drug administration: a preliminary report. Bull World Health Organ 22: 621631. [Google Scholar]
  24. Charoenlarp R, Areekul S, Pholpothi T, Harinasuta T, , 1973. The course of primaquine-induced hemolysis in G-6_PD deficient Thais. J Med Assoc Thail 56: 392397. [Google Scholar]

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  • Received : 07 Nov 2012
  • Accepted : 18 Feb 2013
  • Published online : 05 Jun 2013

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