Iron chelation therapy for malaria: A review

Pharmacology and Therapeutics

Volumn 81, Issue 1, 1999, Pages 53-75

  Mabeza, George F ^a   Loyevsky, Mark ^b   Gordeuk, Victor R ^b   Weiss, Günter ^c  

^a UNIV OF ZIMBABWE MEDICAL SCHOOL   (Zimbabwe)

^b GEORGE WASHINGTON UNIVERSITY   (United States)

^c UNIVERSITY OF INNSBRUCK   (Austria)

Author keywords

Cytokines; Iron chelators; Malaria; Nitric oxide

Indexed keywords

ANTIMALARIAL AGENT; DEFEROXAMINE; HYDRAZONE DERIVATIVE; IRON CHELATING AGENT; SIDEROPHORE;

ANTIMALARIAL ACTIVITY; ERYTHROCYTE; HUMAN; IRON CHELATION; MALARIA; PLASMODIUM FALCIPARUM; PRIORITY JOURNAL; REVIEW; TROPHOZOITE;

ANIMALS; CHELATION THERAPY; HUMANS; IRON; MALARIA, FALCIPARUM; PLASMODIUM FALCIPARUM;

EID: 0032925829     PISSN: 01637258     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0163-7258(98)00037-0     Document Type: Review

References (194)

1. Aikawa M. Fine structure of malaria parasites in the various stages of development. Wernsdorfer W.H., McGregor I. Principles and Practice of Malariology. 1988;97-130 Churchill Livingstone, Edinburgh. a.
2. Aikawa M. Human cerebral malaria. Am. J. Trop. Med. Hyg. 39:1988;3-10. b.
3. Aikawa M., Iseki M., Barnwell J.W., Taylor D., Oo M.M., Howard R.J. The pathology of human cerebral malaria. Am. J. Trop. Med. Hyg. 43(Suppl.):1990;30-37.
4. Albert A. Selective Toxicity. 1981;Chapman and Hill, New York.
5. Alford C.E., King T.E., Campell P.A. Role of transferrin, transferrin receptors, and iron in macrophage listericidal activity. J. Exp. Med. 174:1991;459-466.
6. Alvarez-Hernandez X., Liceaga J., McKay I.C., Brock J.H. Induction of hypoferremia and modulation of macrophage iron. Lab. Invest. 61:1989;319-322.
7. Ambrosio G., Zweier J.L., Jacobus W.E., Weisfeldt M.L., Flaherty J.T. Improvement of post-ischemic myocardial function and metabolism induced by administration of deferoxamine at time of reflow. role of iron in the pathogenesis of reperfusion injury Circulation. 76:1987;906-915.
8. Anonymous (1984) Advances in malaria chemotherapy. Report of a WHO scientific group. World Health Organ. Tech. Rep. Ser. 711: 1-218.
9. Anstey N.M., Weinberg J.B., Hassanali M.Y., Mwaikambo E.D., Manyenga D., Misukonis M.A., Arnelle D.R., Hollis D., McDonald M.I., Granger D.L. Nitric oxide in Tanzanian children with malaria. inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression J. Exp. Med. 184:1996;557-567.
10. Atkinson C.T., Bayne M.T., Gordeuk V.R., Brittenham G.M., Aikawa M. Stage-specific ultrastructural effects of desferrioxamine on Plasmodium falciparum in vitro. Am. J. Trop. Med. Hyg. 45:1991;593-601.
11. Bailey-Wood R., Blayney L.M., Muir J.R., Jacobs A. The effects of iron deficiency on rat liver enzymes. Br. J. Exp. Pathol. 56:1975;193-198.
12. Barnewall R.E., Rikihias Y. Abrogation of gamma interferon-induced inhibiton of Ehrlichia chaffeensis infection in human monocytes with transferrin iron. Infect. Immun. 82:1994;4804-4810.
13. Basco L.K., Le Bras J. In vitro activity of chloroquine and quinine in combination with desferrioxamine against Plasmodium falciparum. Am J. Hematol. 42:1993;389-391.
14. Berendt A.R., Ferguson D.J., Gardner J., Turner G., Rowe A., McCormick C., Roberts D., Craig A., Pinches R., Elford B.C., Newbold C.I. Molecular mechanisms of sequestration in malaria. Parasitology. 108:1994;519-528.
15. Bezkorovainy A. Biochemistry of Nonheme Iron. 1980;Plenum Press, New York and London.
16. Bogdan C., Vodovotz Y., Nathan C. Macrophage deactivation by interleukin 10. J. Exp. Med. 174:1991;1549-1555.
17. Bogdan C., Vodovotz Y., Paik J., Xie Q.W., Nathan C. Mechanism of suppression of nitric oxide synthase by interleukin-4 in primary mouse macrophages. J. Leukocyte Biol. 55:1994;227-232.
18. Bolanos J.P., Heales S.J., Peuchen S., Barker J.E., Land J.M., Clark J.B. Nitric oxide mediated mitochondrial damage. a potential neuroprotective role of glutathione Free Radic. Biol. Med. 21:1996;995-1001.
19. Bonday Z.Q., Taketani S., Gupta P.D., Padmanaban G. Heme biosynthesis by the malarial parasite. Import of delta-aminolevulinate dehydrase from the host red cell. J. Biol. Chem. 272:1997;21839-21846.
20. Bredt D.S., Snyder S.H. Nitric oxide. a physiological messenger Annu. Rev. Biochem. 63:1994;175-195.
21. Brittenham G.M. Iron chelating agents. Brain M.C., Carbone P.P. Current Therapy in Hematology Oncology 3. 1988;149-153 Mosby, St. Louis.
22. Brock J.H. Iron in infection, immunity, inflammation and neoplasia. Brock J.H., Halliday J.W., Pippard M.J., Powell L.W. Iron Metabolism in Health and Disease. 1994;353-389 W. B. Saunders Company Ltd, Philadelphia.
23. Bruce-Chwatt L.J. History of malaria from prehistory to eradication. Wernsdofer W.H., MacGregor I. Malaria - Principles and Practice of Malariology. 1988;1-59 Churchill Livingstone, New York.
24. Bunnag D., Poltera A.A., Viravan C., Looaresuwan S., Harinasuta T., Schundlery C. Plasmodicidal effect of desferrioxamine in human vivax or falciparum malaria from Thailand. Acta Trop. 52:1992;59-67.
25. Byrd T.F., Horwitz M.A. Lactoferrin inhibits or promotes Legionella pneumophila intracellular multiplication in nonactivated and interferon-gamma activated human monocytes depending upon its degree of iron saturation. Iron-lactoferrin and nonphysiologic iron chelates reverse monocyte activation against Legionella pneumophila. J. Clin. Invest. 88:1991;1103-1112.
26. Cabantchik Z.I. Properties of permeation pathways induced in the human red cell membrane by malaria parasites. Blood Cells. 16:1990;421-432.
27. Cabantchik Z.I. Iron chelators as antimalarials - the biochemical basis of selective cytotoxicity. Parasitol. Today. 11:1995;73-78.
28. Cabantchik Z.I., Kutner S., Krugliak M., Ginsburg H. Anion transport inhibitors as supressors of Plasmodium falciparum growth in in vitro cultures. Mol. Pharmacol. 23:1983;92-99.
29. Cabantchik Z.I., Glickstein H., Golenser J., Loyevsky M., Tsafack A. Iron chelators. mode of action as antimalarials Acta Haematol. 95:1996;70-77.
30. Cavanaugh P.F., Porter C.W., Tukalo D., Frankfurt D.S., Pavelic Z.P., Bergeron R.J. Characterization of L1210 cell growth inhibition by the bacterial iron chelators parabactin and compound II. Cancer Res. 45:1985;4754-4759.
31. Cazzola M., Arioso P., Barosi G., Bergamaschi G., Dezza L., Ascari E. Ferritin in the red cells of normal subjects and patients with iron deficiency and iron overload. Br. J. Haematol. 53:1983;659-665.
32. Cenci E., Mencacci A., Del-Sero G., Bistoni F., Romani L. Induction of protective Th1 responses to Candida albicans by antifungal therapy alone or in combination with an interleukin-4 antagonist. J. Infect. Dis. 176:1997;217-226.
33. Chevion M., Chuang L., Golenser J. Effects of zinc-desferrioxamine on Plasmodium falciparum in culture. Antimicrob. Agents Chemother. 39:1995;1902-1905.
34. Clark I.A., Rockett K.A., Cowden W.B. Proposed link between cytokines, nitric oxide and human cerebral malaria. Parasitol. Today. 7:1991;205-207.
35. Clark I.A., Rockett K.A., Cowden W.B. Possible central role of nitric oxide in conditions clinically similar to cerebral malaria. Lancet. 340:1992;894-896.
36. Clarke C.J., Eaton J.M. Hydrophobic iron chelators as new antimalarial drugs. Clin. Res. 38:1990;300A.
37. Clyde D.F. Recent trends in the epidemiology and control of malaria. Epidemiol. Rev. 9:1987;219-243.
38. Cook L., Grant P.T., Kermack W.O. Proteolytic enzymes of the erythrocytic forms of rodent and simian species of malarial plasmodia. Exp. Parasitol. 11:1961;372-379.
39. Cot S., Ringwald P., Mulder B., Yap-Yap J.J., Nüssler A.K., Eling W.M.C. Nitric oxide in cerebral malaria. J. Infect. Dis. 169:1994;1417-1418.
40. de Kossondo S., Grau G. Profiles of cytokine production in relation with susceptibility to cerebral malaria. J. Immunol. 151:1993;4811-4820.
41. Dinarello C.A., Cannon J.G., Mier J.W., Bernheim H.A., Lo Preste G., Lynn D.L., Love R.N., Webb A.C., Auron P.E., Reuben R.C., Rich A., Wolff S.M., Putney S.D. Multiple biological activities of human recombinant interleukin 1. J. Clin. Invest. 77:1986;1734-1739.
42. Drapier J.-C., Hibbs J.B. Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in L-arginine dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effector cells. J. Immunol. 140:1988;2829-2833.
43. Drapier J.-C., Hirling H., Wietzerbin H., Kaldy P., Kühn L.C. Biosynthesis of nitric oxide activates iron regulatory factor in macrophages. EMBO J. 12:1993;3643-3650.
44. Dugas B., Mossalayi M.D., Damais C., Kolb J.P. Nitric oxide production by human monocytes. evidence for a role of CD23 Immunol. Today. 16:1995;574-580.
45. Francis S.E., Banerjee R., Goldberg D.E. Biosynthesis and maturation of the malaria aspartic hemoglobinases plasmepsins I and II. J. Biol. Chem. 272:1997;14961-14968.
46. Fritsch G., Treumer J., Spira D.T., Jung A. Plasmodium vinckei. suppression of mouse infections with deferoxamine B Exp. Parasitol. 60:1985;171-174.
47. Fritsch G., Sawatzki G., Treumer J., Jung A., Spira D.T. Plasmodium falciparum. inhibition in vitro with lactoferrin, desferrithiocin and desferricrocin Exp. Parasitol. 63:1987;1-9.
48. Fuchs D., Hausen A., Reibnegger G., Werner E.R., Deitrich M.P., Wachter H. Neopterin as a marker of activated cell-mediated immunity. application on HIV infection Immunol. Today. 9:1988;150-155.
49. Fuchs O., Ponka P. The role of iron supply in the regulation of 5-aminolevulinate synthase mRNA levels in murine erythroleukemia cells. Neoplasma. 43:1996;31-36.
50. Gabay T., Ginsburg H. Haemoglobin denaturation and iron release in acidified red blood cell lysate - a possible source of iron for intraerythrocytic malaria parasites. Exp. Parasitol. 77:1993;261-272.
51. Gabay T., Krugliak M., Shalmiev G., Ginsburg H. Inhibition by anti-malarial drugs of hemoglobin denaturation and iron release in acidified red blood cell lysates - a possible mechanism of their anti-malarial effect. Parasitology. 108:1994;371-381.
52. Gamboa de Dominguez N., Rosenthal P.J. Cysteine proteinase inhibitors block early steps in hemoglobin degradation by cultured malaria parasites. Blood. 87:1996;4448-4454.
53. Garnham P.C. Malaria parasites in man. life-cycles and morphology (excluding ultrastructure) Wernsdorfer W.H., McGregor I. Principles and Practice of Malariology. 1988;61-96 Churchill Livingstone, Edinburgh.
54. Garthwaite J. Glutamate, nitric oxide and cell-cell signaling in the nervous system. Trends Neurosci. 14:1991;60-67.
55. Gazzinelli R.T., Oswald I.P., James S.L., Sher A. IL-10 inhibits parasite killing and nitrogen production by IFN-gamma-activated macrophages. J. Immunol. 148:1992;1792-1796.
56. Gilles H.M. Management of Severe and Complicated Malaria. A Practical Handbook:1991;World Health Organization, Geneva.
57. Glickstein H., Breuer B., Loyevsky M., Konijn A., Libman J., Shanzer A., Cabantchik Z.I. Differential cytotoxicity of iron chelators on malaria-infected cells versus mammalian cells. Blood. 87:1996;4871-4878.
58. Golenser J., Tsafack A., Amichai Y., Libman J., Shanzer A., Cabantchik Z.I. Antimalarial action of hydroxamate-based iron chelators and potentiation of desferrioxamine action by reversed siderophores. Antimicrob. Agents Chemother. 39:1995;61-65.
59. Golenser J., Domb A., Teomim D., Tsafack A., Nisim O., Ponka P., Eling W., Cabantchik Z.I. The treatment of animal models of malaria with iron chelators by use of a novel polymeric device for slow drug release. J. Pharmacol. Exp. Ther. 281:1997;1127-1135.
60. Goodwin J.F., Whitten C.F. Chelation of ferrous sulfate solutions by desferrioxamine B. Nature. 205:1965;281-283.
61. Gordeuk V.R., Thuma P.E., Brittenham G.M., McLaren C., Parry D., Backenstose A.R., Biemba G., Msiska R., Holmes L., McKinley E., Vargas L., Gilkeson R.C., Poltera A.A. Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria. N. Engl. J. Med. 327:1992;1473-1477. a.
62. Gordeuk V.R., Thuma P.E., Brittenham G.M., Zulu S., Simwanza G., Mhangu A., Flesch G., Parry D. Iron chelation with deferoxamine B in adults with asymptomatic Plasmodium falciparum parasitemia. Blood. 79:1992;308-312. b.
63. Gordeuk V.R., Thuma P.E., Brittenham G.M., Biemba G., Zulu S., Simwanza G., Kalense P., M'hango A., Parry D., Poltera A.A., Aikawa M. Iron chelation as a chemotherapeutic strategy for falciparum malaria. Am. J. Trop. Med. Hyg. 48:1993;193-197.
64. Gordeuk V.R., Thuma P.E., McLaren C.E., Biemba G., Zulu S., Poltera A.A., Askin J.E., Brittenham G.M. Transferrin saturation and recovery from coma in cerebral malaria. Blood. 85:1995;3297-3301.
65. Haldar K., Henderson C.L., Cross G.A. Identification of the parasite transferrin receptor of Plasmodium falciparum infected erythrocytes and its acylation via 1,2-diacyl-Sn-glycerol. Proc. Natl. Acad. Sci. USA. 83:1986;8565-8569.
66. Halliwell B., Gutteridge J.M.C., Cross C.E. Free radicals, antioxidants and human disease. Where are we now? J. Lab. Clin. Med. 119:1992;598-620.
67. Harvey P.W., Heywood P.F., Nesheim M.C., Galme K., Zegans M., Habicht J.-P., Stephenson L.S., Radimer K.L., Brabin B., Forsyth K., Alpers M.P. The effect of iron therapy on malarial infection in Papua New Guinean schoolchildren. Am. J. Trop. Med. Hyg. 40:1989;12-18.
68. Henson P.M., Johnson R.B. Tissue injury in inflammation. oxidants, proteinases, and cationic proteins J. Clin. Invest. 79:1987;669-674.
69. Hentze M.W., Kühn L.C. Molecular control of vertebrate iron metabolism. mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress Proc. Natl. Acad. Sci. USA. 93:1996;8175-8182.
70. Heppner D.G., Hallaway P.E., Kontoghiorghes G.J., Eaton J.W. Antimalarial properties of orally active iron chelators. Blood. 72:1988;358-361.
71. Hershko C., Peto T.E. Deferoxamine inhibition of malaria is independent of host iron status. J. Exp. Med. 168:1988;375-387.
72. Hershko C., Theanacho E.N., Spira D.T., Peter H.H., Dobbin P., Hider R.C. The effect of N-alkyl modification on the antimalarial activity of 3-hydroxypyridin-4-one oral iron chelators. Blood. 77:1991;637-643.
73. Hershko C., Gordeuk V.R., Thuma P.E., Theanacho E.N., Spira D.T., Hider R.C., Peto T.E., Brittenham G.M. The anti-malarial effect of iron chelators in animal models and in humans with mild falciparum malaria. J. Inorg. Biochem. 47:1992;267-277.
74. Hibbs J.B., Taintor R.R., Vavrin Z., Rachlin E.M. Nitric oxide. a cytotoxic activated macrophage effector molecule Biochem. Biophys. Res. Commun. 157:1987;87-94.
75. Hoffbrand A.V., Ganeshaguru K., Hooton J.W., Tattersall M.H. Effect of iron deficiency and desferrioxamine on DNA synthesis in human cells. Br. J. Haematol. 33:1976;517-526.
76. Huber C., Batchelor J.R., Fuchs D., Hausen A., Lang A., Niederwieser D., Reibnegger G., Swetly P., Troppmair J., Wachter H. Immune response associated production of neopterin. J. Exp. Med. 160:1984;310-316.
77. Hudson-Taylor D.E., Dolan S.A., Klotz F.W., Fujioka H., Aikawa M., Koonin E.V., Miller L.H. Plasmodium falciparum protein associated with the invasion junction contains a conserved oxidoreductase domain. Mol. Microbiol. 15:1995;463-471.
78. Ignarro L.J. Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu. Rev. Pharmacol. Toxicol. 30:1990;535-560.
79. Jacobs P., Radzioch D., Stevenson M.M. In vivo regulation of nitric oxide production by tumor necrosis factor alpha and gamma interferon but not by interleukin 4, during blood stage malaria in mice. Infect. Immun. 64:1996;44-49.
80. Jairam K.T., Havlik I., Monteagudo F.S.E. Possible mechanism of action of desferrioxamine and 2,2′-bipyridyl on inhibiting the in vitro growth of Plasmodium falciparum (3 strain). Biochem. Pharmacol. 8:1991;1633-1634.
81. Jambou R., Ghogomu N.A., Kouka-Bemba K., Hengy C. Activity of chloroquine and desferrioxamine in vitro against newly isolated Plasmodium falciparum and their antagonism in combination. Trans. R. Soc. Trop. Med. Hyg. 86:1992;11.
82. Kanegawa O., Vaupel B.A., Gayama S., Koehler G., Kopf M. Resistance of mice deficient in IL-4 to retrovirus induced immunodeficiency syndrome (MAIDS). Science. 263:1993;240-242.
83. Karupiah G., Harris N. Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid cycle metabolites. J. Exp. Med. 181:1995;2171-2179.
84. Klausner R., Rouault T.A., Harford J.B. Regulating the fate of mRNA. the control of cellular iron metabolism Cell. 72:1993;19-22.
85. Kolakovich K.A., Gluzman I.Y., Duffin K.L., Goldberg D.E. Generation of hemoglobin peptides in the acidic digestive vacuole of Plasmodium falciparum implicates peptide transport in amino acid production. Mol. Biochem. Parasitol. 87:1997;123-135.
86. Kontoghiorghes G.J., Hoffbrand A.V. Orally active alpha ketohydroxyl pyridine iron chelators intended for clinical use. in vivo studies in rabbits Br. J. Haematol. 62:1986;607-613.
87. Kremsner P.G., Winkler S., Wildling E. High plasma levels of nitrogen oxides are associated with severe disease and correlate with rapid parasitological and clinical cure in Plasmodium falciparum malaria. Trans. R. Soc. Trop. Med. Hyg. 90:1996;44-47.
88. Kröncke K.D., Fehsel K., Kolb-Bachofen V. Nitric oxide. cytotoxicity versus cytoprotection - How, Why, When, and Where? Nitric Oxide. 1:1997;107-120.
89. Kwon N.S., Stuehr D.J., Nathan C.F. Inhibition of tumor cell ribonucleotide reductase by macrophage derived nitric oxide. J. Exp. Med. 174:1991;761-767.
90. Lancaster J.R., Hibbs J.B. EPR demonstrations of iron nitrosyl complexes by cytotoxic activated macrophages. Proc. Natl. Acad. Sci. USA. 87:1990;1223-1227.
91. Laskey J.D., Ponka P., Schulman H.M. Control of heme synthesis during Friend cell differentiation. role of iron and transferrin J. Cell. Physiol. 129:1986;185-192.
92. Leal L.M., Moss D.W., Kuhn R., Müller W., Liew F.Y. Interleukin-4 transgeneic mice of resistant background are susceptible to Leishmania major infection. Eur. J. Immunol. 23:1993;566-569.
93. Lepoviere M., Chenais B., Yago G., Lemaire L., Thelander L., Tenu J.P. Alteration of ribonucleotide reductase activity following induction of the nitrite-generating pathway in adenocarcinoma cells. J. Biol. Chem. 265:1990;14143-14149.
94. Liew F.Y. The role of nitric oxide in parasitic diseases. Ann. Trop. Med. Parasitol. 87:1993;637-642.
95. Loyevsky M., Lytton S.D., Mester B., Libman J., Shanzer A., Cabantchik Z.I. The antimalarial action of Desferal involves a direct access route to erythrocytic (Plasmodium falciparum) parasites. J. Clin. Invest. 91:1993;218-224.
96. Loyevsky M., John C., Zaloujnyi I., Gordeuk V. Aminothiol multidentate chelators as antimalarials. Biochem. Pharmacol. 54:1997;451-458.
97. Lytton S.D., Cabantchik I., Libman J., Shanzer A. Reversed siderophores as antimalarial agents. II. Selective scavenging of Fe(III) from parasitized erythrocytes by a fluorescent derivative of Desferal. Mol. Pharmacol. 40:1991;584-590.
98. Lytton S.D., Loyevsky M., Mester B., Libman J., Landau I., Shanzer A., Cabantchik Z.I. In vivo antimalarial action of a lipophilic iron(III) chelator. suppression of Plasmodium vinckei infection by reversed siderophore Am. J. Hematol. 43:1993;217-220. a.
99. Lytton S.D., Mester B., Dayan I., Glickstein H., Libman J., Shanzer A., Cabantchik Z.I. Mode of action of iron(III) chelators as antimalarials. I. Membrane permeation properties and cytotoxic activity Blood. 81:1993;214-221. b.
100. Lytton S.D., Mester B., Libman J., Shanzer A., Cabantchik Z.I. Mode of action of iron(III) chelators as antimalarials. II. Evidence for differential effects on parasite iron-dependent nucleic acid synthesis. Blood. 84:1994;910-915.
101. MacPherson G.G., Warrell M.J., White N.J., Looareesuwan S., Warrell D.A. Human cerebral malaria. a quantitative ultrastructural analysis of parasitized erythrocyte sequestration Am. J. Pathol. 119:1985;385-401.
102. Matsui D., Klein J., Hermann C., Grunau V., McClelland R., Chung D., St-Louis P., Olivieri N., Koren G. Relationship between the pharmacokinetics and iron excretion pharmacodynamics of the new oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with thalassemia. Clin. Pharmacol. Ther. 50:1991;294-298.
103. McCord J.M. Oxygen-derived free radicals in postischemic tissue injury. N. Engl. J. Med. 312:1985;159-163.
104. Means R.T., Krantz S.B. Progress in understanding the pathogenesis of anemia of chronic disease. Blood. 80:1992;1639-1646.
105. Mellouk S., Green S.J., Nacy C.A., Hoffman S.L. IFN-gamma inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocytes by a L-arginine dependent pathway. J. Immunol. 146:1991;3971-3976.
106. Mellouk S., Hoffman S.L., Liu Z.Z., DeLaVega P., Billiar T., Nussler A.K. Nitric oxide mediated antiplasmodial activity in human and murine hepatocytes by gamma interferon and the parasite itself. enhancement by exogenous tetrahydrobiopterin Infect. Immun. 62:1994;4043-4046.
107. Modell B., Berdoukas V. The Clinical Approach to Thalassemia. 1984;Grune and Stratton, London.
108. Modolell M., Corraliza I.M., Link F., Soler G., Eichmann K. Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH1 and Th2 cytokines. Eur. J. Immunol. 25:1995;1101-1104.
109. Molyneux M.E., Taylor T.E., Wirima J.J., Borgstein A. Clinical features and prognostic indicators in paediatric cerebral malaria. a study of 131 comatose Malawian children, Q J. Med. New Series. 71:1989;441-459.
110. Moncada S., Higgs E. The L-arginine-nitric oxide pathway. N. Engl. J. Med. 329:1993;2002-2011.
111. Mosmann T.R., Coffman R.L. Th1 and Th2 cells. different patterns of lymphokine secretion leads to different functional properties Annu. Rev. Immunol. 7:1989;145-173.
112. Murray M.J., Murray A.B., Murray M.B., Murray C.J. Refeeding malaria and hyperferraemia. Lancet i: 653-654:1975.
113. Murray M.J., Murray A.B., Murray M.B., Murray C.J. The adverse effect of iron repletion on the course of certain infections. Br. Med. J. 2:1978;1113-1115.
114. Nathan C.F. Nitric oxide as a secretory product of mammalian cells. FASEB J. 6:1992;3051-3064.
115. Nathan C.F., Xie Q.-W. Nitric oxide synthases. roles, tolls and controls Cell. 78:1994;915-918.
116. Neilands J.B. Siderophores. structure and function of microbial iron transport compounds J. Biol. Chem. 270:1995;26723-26726.
117. Nicholson S., Bonecini-Almeida M.G., Lapa-e-Silva J.R., Nathan C., Xie Q.W., Mumford R., Weidner J.R., Calaycay J., Geng J., Boechat N. Inducible nitric oxide synthase in pulmonary alveolar macrophages from patients with tuberculosis. J. Exp. Med. 183:1996;2293-2302.
118. Nordlund P., Sjoberg B.-M., Eklund H. Three-dimensional structure of the free radical protein of ribonucleotide reductase. Nature. 345:1990;593-598.
119. Nüssler A., Drapier J.-C., Renia L., Pied S., Miltgen F., Gentilini M., Mazier D. L-Arginine dependent destruction of intrahepatic malaria parasites in response to tumor necrosis factor and/or interleukin 6 stimulation. Eur. J. Immunol. 21:1991;227-230.
120. Nüssler A.K., Eling W., Kremsner P.G. Patients with Plasmodium falciparum malaria and Plasmodium vivax malaria show increased nitrite and nitrate plasma levels. J. Infect. Dis. 169:1994;1419-1420.
121. Nyholm S., Mann G.J., Johansson A.G., Bergeron R.J., Graslund A., Thelander L. Role of ribonucleotide reductase in inhibition of mammalian cell growth by potent iron chelators. J. Biol. Chem. 268:1993;26200-26205.
122. Olivieri N.F. Long-term therapy with deferiprone. Acta Haematol. 95:1996;37-48.
123. Oo M.M., Aikawa M., Than T., Aye T.M., Myint P.T., Igarashi I., Schoene W.C. Human cerebral malaria. a pathological study J. Neuropathol. Exp. Neurol. 46:1987;223-231.
124. Oppenheimer S.J., Gibson F.D., MacFarlane S.B., Moody J.B., Harrison C., Spencer A., Bunari O. Iron supplementation increases prevalence and effects of malaria. report on clinical studies in Papua New Guinea Trans. R. Soc. Trop. Med. Hyg. 80:1986;603-612. a.
125. Oppenheimer J.L., MacFarlane S.B., Moody J.B., Harrison C. Total dose iron infusion, malaria and pregnancy in Papua New Guinea. Trans. R. Soc. Trop. Med. Hyg. 80:1986;818-822. b.
126. Pantopoulos K., Hentze M.W. Nitric oxide signaling to iron regulatory protein. direct control of ferritin mRNA translation and transferrin receptor mRNA stability in transfected fibroblasts Proc. Natl. Acad. Sci. USA. 92:1995;1267-1271.
127. Patarroyo M.E., Amador R., Clavijo P., Moreno A., Guzman F., Romero P., Tascon R., Franco A., Murillo L.A., Ponton G., Trujillo G. A synthetic vaccine protects humans against challenge with asexual blood stages of Plasmodium falciparum malaria. Nature. 332:1988;158-161.
128. Pattanapanyasat K., Thaithong S., Kyle D.E., Udomsangpetch R., Yongvanitchit K., Hider R.C., Webster H.K. Flow cytometric assessment of hydroxypyridone iron chelators on in vitro growth of drug-resistant malaria. Cytometry. 27:1997;84-91.
129. Peto T.E., Thompson J.L. A reappraisal of the effects of iron and desferrioxamine on the growth of Plasmodium falciparum "in vitro" the unimportance of serum iron Br. J. Haematol. 63:1986;273-280.
130. Pollack S., Flemming J. P. falciparum takes up iron from transferrin. Br. J. Haematol. 58:1984;289-293.
131. Pollack S., Schnelle V. Inability to detect transferrin receptors on P. falciparum parasitized red cells. Br. J. Haematol. 68:1988;125-129.
132. Pollack S., Rossan R.N., Davidson D.E., Escajadillo A. Desferrioxamine suppresses Plasmodium falciparum in aotus monkeys. Proc. Soc. Exp. Biol. Med. 184:1987;162-164.
133. Ponka P., Richardson D.R., Edward J.T., Chubb F.L. Iron chelators of the pyridoxal isonycotinoyl hydrazone class. Relationship of the lipophilicity of the apochelator to its ability to mobilize iron from reticulocytes in vitro. Can. J. Physiol. Pharmacol. 72:1994;659-666.
134. Pootrakul P., Kitcharoen K., Yansukon P., Fucharoen S., Charoenlarp P., Brittenham G., Pippard M.J., Finch C.A. The effect of erythroid hyperplasia on iron balance. Blood. 71:1988;1124-1129.
135. Porter J.B., Gyparaki M., Huehns E.R., Hider R.C. The relationship between the lipophilicity of hydroxypyrid-4-one iron chelators and cellular iron metabolism using an hepatocyte culture model. Biochem. Soc. Trans. 14:1986;1180.
136. Pouvelle B., Spiegel R., Hsiao L., Howard R.J., Morris R.L., Thomas A.P., Taraschi T.F. Direct access to serum macromolecules by intraerythrocytic malaria parasites. Nature. 353:1991;73-75.
137. Powrie F., Menon S., Coffman R.L. Interleukin-4 and interleukin-10 synergize to inhibit cell-mediated immunity in vivo. Eur. J. Immunol. 23:1993;2223-2229.
138. Pradines B., Ramiandrasoa F., Basco L.K., Bricard L., Kunesh G., Le-Bras J. In vitro activities of novel catecholate siderophores against Plasmodium falciparum. Antimicrob. Agents Chemother. 40:1996;2094-2098.
139. Raventos-Suarez C., Pollack S., Nagel R.L. Plasmodium falciparum. inhibition of in vitro growth by desferrioxamine Am. J. Trop. Med. Hyg. 31:1982;919-922.
140. Reichard P., Ehrenburg A. Ribonucleotide reductase - a radical enzyme. Science. 221:1983;514-519.
141. Reif D.W., Simmons R.D. Nitric oxide mediates iron release from ferritin. Arch. Biochem. Biophys. 283:1990;537-542.
142. Rockett K.A., Awburn M.M., Cowden W.B., Clark I.A. Killing of Plasmodium falciparum in vitro by nitric oxide derivatives. Infect. Immun. 59:1991;3280-3286.
143. Rodriguez M.H., Jungery M.H. A protein of Plasmodium falciparum-infected erythrocytes functions as a transferrin receptor. Nature. 324:1986;388-391.
144. Romagnagi S. The Th1/Th2 paradigm. Immunol. Today. 18:1997;263-266.
145. Rosen G.M., Pou S., Ramos C.L., Cohen M.S., Britigan B.E. Free radicals and phagocytic cells. FASEB J. 9:1995;200-209.
146. Rubin H., Salem H.S., Li L.S., Yang F.D., Mama S., Wang Z.M., Fisher A., Hamann C.S., Cooperman B.S. Cloning, sequence determination, and regulation of the ribonucleotide reductase subunits from Plasmodium falciparum. a target for antimalarial therapy Proc. Natl. Acad. Sci. USA. 90:1993;9280-9284.
147. Sadrzadeh S.M., Graf E., Panter S.S., Hallaway P.E., Eaton J.W. Hemoglobin. a biologic Fenton reagent J. Biol. Chem. 259:1984;14354-14356.
148. Sadrzadeh S.M., Anderson D.K., Panter S.S., Hallaway P.E., Eaton J.W. Hemoglobin potentiates central nervous system damage. J. Clin. Invest. 79:1987;662-664.
149. Sanchez-Lopez R., Halder K. A transferrin-independent iron uptake activity in Plasmodium falciparum-infected and uninfected erythrocytes. Mol. Biochem. Pharmacol. 55:1992;9-20.
150. Scheibel L.W., Adler A. Anti-malarial activity of selected aromatic chelators. Mol. Pharmacol. 18:1980;320-325.
151. Scheibel L.W., Rodriguez S. Anti-malarial activity of selected aromatic chelators. V. Localization of 59Fe in Plasmodium falciparum in the presence of oxines. Prog. Clin. Biol. Res. 313:1989;119-149.
152. Scheibel L.W., Sherman I.W. Metabolism and organellar function during various stages of the life cycle. proteins, lipids, nucleic acids and vitamins Wernsdorfer W., McGregor I. Malaria - Principles and Practice of Malariology. 1988;219-252 Churchill Livingstone, New York.
153. Scheibel L.W., Stanton G.G. Anti-malarial activity of selected aromatic chelators IV. Cation uptake of Plasmodium falciparum in the presence of oxines and siderochromes. Mol. Pharmacol. 30:1986;364-369.
154. Scheibel L.W., Adler A., Trager W. Tetraethylthiuram disulfide (Antabuse) inhibits the human malaria parasite Plasmodium falciparum. Proc. Natl. Acad. Sci. USA. 76:1979;5303-5307.
155. Scott M.D., Ranz A., Kuypers F.A., Lubin B.H., Meshnick S.R. Parasite uptake of desferrioxamine. a prerequisite for antimalarial activity Br. J. Haematol. 75:1990;598-603.
156. Seder R.A., Paul W.E. Acquisition of lymphokine-producing phenotype by CD4+ cells. Annu. Rev. Immunol. 12:1994;635-673.
157. Seguin M.C., Klotz F.W., Schnieder I., Weir J.P., Goodbary M., Slayter M., Raney J.J., Aniagolu J.U., Green S.J. Induction of nitric oxide synthase protects against malaria in mice exposed to irradiated Plasmodium berghei infected mosquitoes. involvement of interferon gamma and CD8+ cells J. Exp. Med. 180:1994;353-358.
158. Shanzer A., Libman J., Lytton S.D., Glickstein H., Cabantchik Z.I. Reversed siderophores act as anti-malarial agents. Proc. Natl. Acad. Sci. USA. 88:1991;6585-6589.
159. Sharara A.I., Perkins D.J., Misukonis M.A., Chan S.U., Dominitz J.A., Weinberg J.B. Interferon-α activation of human blood mononuclear cells in vitro and in vivo for nitric oxide synthase (NOS) Type 2 mRNA and protein expression. possible relationship of induced NOS2 to the anti-hepatitis C effects of interferon-α in vivo. J. Exp. Med. 186:1997;1495-1502.
160. Silfen J., Yanai P., Cabantchik Z.I. Bioflavonoid effects on in vitro cultures of Plasmodium falciparum. Inhibition of permeation pathways induced in the host cell membrane by the intraerythrocytic parasite. Biochem. Pharmacol. 37:1988;4269-4276.
161. Singh S., Hider R.C. Therapeutic iron-chelating agents. Rice-Evans C.A., Burdon R.H. Free Radical Damage and Its Control. 1994;189-216 Elsevier Science, New York.
162. Slater A.F., Cerami A. Inhibition by chloroquine of a novel heme polymerase enzyme activity in malaria trophozoites. Nature. 355:1992;167-169.
163. Srivastava P., Pandey V.C. Heme oxygenase and related indices in chloroquine-resistant and -sensitive strains of Plasmodium berghei. Int. J. Parasitol. 25:1995;1061-1064.
164. Stahel E., Mazier D., Guillouzo A., Miltgen P., Landau I., Mellouk S., Beaudoin R.L., Langlois P., Gentilini M. Iron chelators. in vitro inhibitory effect on the liver stage of rodent and human malaria Am. J. Trop. Med. Hyg. 39:1988;236-240.
165. Stenger S., Thüring H., Röllinghoff M., Bogdan C. Tissue expression of inducible nitric oxide synthase is closely associated with resistance to Leishmania major. J. Exp. Med. 180:1994;783-793.
166. Stoute J.A., Slaoui M., Heppner D.G., Momin P., Kester K.E., Desmons P., Wellde B.T., Garcon N., Krzych U., Marchand M., Ballou W.R., Cohen J.D. A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. N. Engl. J. Med. 336:1997;86-91.
167. Stuehr D., Nathan C.F. Nitric oxide. a macrophage product responsible for cytostasis and respiratory inhibition of tumor target cells J. Exp. Med. 169:1989;1543-1555.
168. Summers M., Jacobs A., Tudway D., Perera P., Ricketts C. Studies in desferrioxamine and ferrioxamine in normal and iron-loaded subjects. Br. J. Haematol. 42:1979;547-555.
169. Surolia N., Padmanaban G. De novo biosynthesis of heme offers a new chemotherapeutic target in the human malarial parasite. Biochem. Biophys. Res. Commun. 187:1992;744-750.
170. Tanner M., Teuscher T., Alonso P.L. SPf66 - The first malaria vaccine. Parasitol. Today. 11:1995;10-13.
171. Taylor-Robinson A.W., Phillips R.S., Severn A., Moncada S., Liew F.Y. The role of TH1 and TH2 cells in a rodent malaria infection. Science. 260:1993;1931-1934.
172. Thuma P.E., Weiss G., Herold M., Gordeuk V. Serum neopterin, interleukin-4 and interleukin-6 concentrations in cerebral malaria patients and the effect of iron chelation therapy. Am. J. Trop. Med. Hyg. 54:1996;164-168.
173. Thuma P.E., Mabeza G.F., Biemba G., Bhat G.J., McLaren C., Moyo V.M., Zulu S., Khumalo H., Mabeza P., M'hango A., Parry D., Poltera A.A., Brittenham G.M., Gordeuk V.R. Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria. Trans. R. Soc. Trop. Med. Hyg. in press:1998;. a.
174. Thuma P.E., Olivieri N.F., Mabeza G.F., Biemba G., Parry D., Zulu S., Fassos F.F., McClelland R.A., Koren G., Brittenham G.M., Gordeuk V.R. Assessment of the effect of the oral iron chelator deferiprone on mild Plasmodium falciparum parasitaemia in humans. Am. J. Trop. Med. Hyg. 58:1998;358-364. b.
175. Traore O., Carnevale P., Kaptue-Noche L., M'Bede J., Desfontaine M., Elion J., Labie D., Nagel R.L. Preliminary report on the use of desferrioxamine in the treatment of Plasmodium falciparum malaria. Am. J. Hematol. 37:1991;206-208.
176. Tsafack A., Loyevsky M., Ponka P., Cabantchik Z.I. Mode of action of iron(III) chelators as anti-malarials. IV. Potentiation of desferal action by
177. van Zyl R.L., Havlik I., Monteagudo F.S.E. The combined effect of iron chelators and classical antimalarials on the in-vitro growth of Plasmodium falciparum. J. Antimicrob. Chemother. 30:1992;273-278.
178. van Zyl R.L., Havlik I., Hempelman E., MacPhail A.P., McNamara L. Malaria pigment and extracellular iron. possible target for iron chelating agents Biochem. Pharmacol. 45:1993;1431-1436.
179. Wang Z.-E., Reiner S.L., Zheng S., Dalton D.K., Locksley R.M. CD4+ effector cells default to the TH2 pathway in interferon gamma-deficient mice infected with Leishmania major. J. Exp. Med. 179:1994;1367-1371.
180. Ward P.A., Till G.O., Kunkel R., Beauchamp C. Evidence for role of hydroxyl radical in complement and neutrophil-dependent injury. J. Clin. Invest. 72:1983;369-371.
181. Weiss G., Fuchs D., Hausen A., Reibnegger G., Werner E.R., Werner-Felmayer G., Wachter H. Iron modulates interferon-gamma effects in human myelomonocytic cell line THP-1. Exp. Hematol. 20:1992;605-610.
182. Weiss G., Goossen B., Doppler W., Fuchs D., Pantopoulos K., Werner-Felmayer G., Wachter H., Hentze M.W. Translational regulation via iron-responsive elements by nitric oxide/NO-synthase pathway. EMBO J. 12:1993;3651-3657.
183. Weiss G., Werner-Felmayer G., Werner E.R., Grünewald K., Wachter H., Hentze M.W. Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J. Exp. Med. 180:1994;969-976.
184. Weiss G., Wachter H., Fuchs D. Linkage of cell-mediated immunity to iron metabolism. Immunol. Today. 16:1995;495-500.
185. Weiss G., Thuma P., Mabeza G., Werner E.R., Herold M., Gordeuk V.R. Modulatory potential of iron chelation therapy on nitric oxide formation in cerebral malaria. J. Infect. Dis. 175:1997;226-230.
186. Weiss G., Thuma P.E., Biemba G., Mabeza G., Werner E.R., Gordeuk V.R. Cerebrospinal fluid levels of biopterin, nitric oxide metabolites, and immune activation markers and the clinical course of human cerebral malaria. J. Infect. Dis. 177:1998;1064-1068.
187. Werner E.R., Werner-Felmayer G., Fuchs D., Hausen A., Reibnegger G., Wachter H. Parallel induction of tetrahydrobiopterin biosynthesis and indoleamine 2,3-dioxygenase activity in human cells and cell lines by interferon-gamma. Biochem. J. 262:1989;861-866.
188. White N.J., Warrell D.A., Looareesuwan S., Chanthavanich P., Phillips R.E., Pongpaew P. Pathophysiological and prognostic significance of cerebrospinal fluid lactate in cerebral malaria. Lancet i: 776-778:1985.
189. Whitehead S., Peto T.E. Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro. Blood. 76:1990;1250-1255.
190. Wilson C.M., Smith A.B., Baylon R.V. Characterization of the delta-aminolevulinate synthase gene homologue in P. falciparum. Mol. Biochem. Parasitol. 75:1996;271-275.
191. World Health Organization (1995) Twelfth programme report of the UNDP/World Bank/WHO special programme for research and training in tropical diseases (TDR). Bull. WHO 12: 64-76.
192. Wrigglesworth J.M., Baum H. The biochemical functions of iron. Jacobs A., Worwood M. Iron in Biochemistry and Medicine II. 1980;29-86 Academic Press, New York.
193. Yang Y., Ranz A., Pan H.Z., Zhang Z.N., Lin X.B., Meshnick S.R. Daphnetin. a novel anti-malarial agent with in vitro and in vivo activity Am. J. Trop. Med. Hyg. 46:1992;15-20.
194. Yinnon A.M., Theanacho E.N., Grady R.W., Spira D.T., Hershko C. Antimalarial effect of HBED and other phenolic and catecholic iron chelators. Blood. 74:1989;2166-2171.