期刊论文详细信息
BMC Clinical Pharmacology
Desferrioxamine decreases NAD redox potential of intact red blood cells: evidence for desferrioxamine as an inducer of oxidant stress in red blood cells
Amy Tu2  Huiyuan Wu2  Oded Shalev1  Junli Ge2  Yutaka Niihara2 
[1]Department of Medicine, Hadassah-Mt. Scopus, Jerusalem, Israel
[2]Department of Medicine, Harbor-UCLA Medical Center, UCLA School of Medicine, Torrance, California, USA
关键词: iron;    oxidant stress;    NAD redox potential;    desferrioxamine;    red blood cells;   
Others  :  1085513
DOI  :  10.1186/1472-6904-2-8
 received in 2002-04-15, accepted in 2002-10-24,  发布年份 2002
PDF
【 摘 要 】

Background

Desferrioxamine (DFO) is an important iron chelating agent. It has also been thought of as an agent with anti-oxidant potential as it chelates ferric iron in various parts of the body. However, there is evidence suggesting that it may paradoxically affect red blood cells (RBC) by inducing intracellular oxidant stress. To further understand the mechanism of DFO's interaction with RBC, we conducted a study to determine the effect of DFO upon RBC's redox status.

Methods

We examined NAD redox potential in intact RBC (N = 5) incubated with DFO. RBC were incubated with 6 mM DFO for 2 hours.

Results

Significant decreases in NAD redox potential were observed after incubation of RBC with 6 mM DFO. The mean decrease was 10.01 ± 1.98% (p < 0.0004).

Conclusions

The data confirm the oxidant effect of DFO on RBC.

【 授权许可】

   
2002 Niihara et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 预 览 】
附件列表
Files Size Format View
20150113174108318.pdf 252KB PDF download
Figure 1. 15KB Image download
【 图 表 】

Figure 1.

【 参考文献 】
  • [1]Goodwin JF, Whitten CF: Chelation of ferrous sulphate solutions by desferrioxamine B. Nature 1965, 205:281(Abstr).
  • [2]Blake DR, Hall ND, Bacon PA, Dieppe PA, Halliwell B, Gutteridge JM: Effect of a specific iron chelating agent on animal models of inflammation. Ann Rheum Dis 1983, 42:89-93.
  • [3]Hamilton KO, Stallibrass L, Hassan I, Jin Y, Halleux C, Mackay M: The transport of two iron chelators, desferrioxamine B and L1, across Caco-2 monolayers. Br J Haematol 1994, 86:851-7.
  • [4]Minotti G, Aust SD: The role of iron in the initiation of lipid peroxidation. Chem Phys Lipids 1987, 44:191-208.
  • [5]Rachidi S, Coudray C, Baret P, Gelon G, Pierre JL, Favier A: Inhibition of lipid peroxidation by a new family of iron chelators. Comparison with desferrioxamine. Biol Trace Elem Res 1994, 41:77-87.
  • [6]Winterbourn CC, Vile GF, Monteiro HP: Ferritin, lipid peroxidation and redox-cycling xenobiotics. Free Radic Res Commun 1991, 12–13(Pt 1):107-14.
  • [7]Klebanoff SJ, Waltersdorph AM, Michel BR, Rosen H: Oxygen-based free radical generation by ferrous ions and deferoxamine. J Biol Chem 1989, 264:19765-71.
  • [8]Mordente A, Meucci E, Miggiano GA, Martorana GE: Prooxidant action of desferrioxamine: enhancement of alkaline phosphatase inactivation by interaction with ascorbate system. Arch Biochem Biophys 1990, 277:234-40.
  • [9]Blake DR, Winyard P, Lunec J, Williams A, Good PA, Crewes SJ, Gutteridge JM, Rowley D, Halliwell B, Cornish A, et al.: Cerebral and ocular toxicity induced by desferrioxamine. Q J Med 1985, 56:345-55.
  • [10]Davies MJ, Donkor R, Dunster CA, Gee CA, Jonas S, Willson RL: Desferrioxamine (Desferal) and superoxide free radicals. Formation of an enzyme-damaging nitroxide. Biochem J 1987, 246:725-9.
  • [11]Yoshino S, Blake DR, Bacon PA: The effect of desferrioxamine on antigen-induced inflammation in the rat air pouch. J Pharm Pharmacol 1984, 36:543-5.
  • [12]Bergamini S, Rota C, Staffieri M, Tomasi A, Iannone A: Prooxidant activity of ferrioxamine in isolated rat hepatocytes and linoleic acid micelles. Chem Res Toxicol 1999, 12:365-70.
  • [13]Niihara Y, Shalev O, Hebbel RP, Wu H, Tu A, Akiyama DS, Tanaka KR: Desferrioxamine (DFO) conjugated with starch decreases NAD redox potential of intact red blood cells (RBC): evidence for DFO as an extracellular inducer of oxidant stress in RBC. Am J Hematol 2000, 65:281-4.
  • [14]Zerez CR, Lee SJ, Tanaka KR: Spectrophotometric determination of oxidized and reduced pyridine nucleotides in erythrocytes using a single extraction procedure. Anal Biochem 1987, 164:367-73.
  • [15]Niihara Y, Zerez CR, Akiyama DS, Tanaka KR: Oral L-glutamine therapy for sickle cell anemia: I. Subjective clinical improvement and favorable change in red cell NAD redox potential. Am J Hematol 1998, 58:117-21.
  • [16]Jaffe ER, Hultquist DE: Metabolic and Molecular Basis of Inherited Disease. Cytochrome b5 reductase deficiency and enzymopenic hereditary methemoglobinemia. In New York, McGraw-Hill Edited by CR Scriver, AL Beaudet, WS Sly, D Valle. 1995, 3399-3415.
  • [17]Gutteridge JM, Paterson SK, Segal AW, Halliwell B: Inhibition of lipid peroxidation by the iron-binding protein lactoferrin. Biochem J 1981, 199:259-61.
  • [18]Wills ED: Mechanisms of lipid peroxide formation in animal tissues. Biochem J 1966, 99:667-76.
  • [19]Hinojosa O, Jacks TJ, Calamari TA, Thibodeaux DP: Electron spin resonance study of the relationship of UV irradiation to nitroxide radical formation in desferrioxamine (Desferal) and related hydroxamate and hydroxylamine derivatives. Photochem Photobiol 1989, 49:1-5.
  • [20]Borg DC, Schaich KM: Prooxidant action of desferrioxamine: Fenton-like production of hydroxyl radicals by reduced ferrioxamine. J Free Radic Biol Med 1986, 2:237-43.
  • [21]Morehouse KM, Flitter WD, Mason RP: The enzymatic oxidation of Desferal to a nitroxide free radical. FEBS Lett 1987, 222:246-50.
  文献评价指标  
  下载次数:13次 浏览次数:30次