|
|
 Previous Article | Table of Contents | Next Article 
Comparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4- one
iron chelators in overloaded and nonoverloaded mice
JB Porter, KP Hoyes, RD Abeysinghe, PN Brooks, ER Huehns and RC Hider
Department of Clinical Haematology, University College and Middlesex School
of Medicine, London, UK.
Five orally effective iron chelators of the 3-hydroxypyridin-4-one series
have been administered intraperitoneally to iron-overloaded and
nonoverloaded male mice at a dose of 200 mg/kg/24 h for a total of 60 days
to investigate the effect on iron loading and toxicity. There was a
significant reduction in hepatic iron at the end of the study in the
iron-overloaded mice with all compounds studied using chemical iron
quantitation (P less than .001) and with Perls' stain (P less than .01).
Liver iron removal with the hydroxypyridinones ranged from 37% with CP20 to
63% with CP51, compared with 46% removal for desferrioxamine (DFO). There
was no significant reduction in splenic or cardiac iron with any chelator.
There were no deaths in iron-overloaded animals receiving any of the
hydroxypyridin-4-ones, but significantly more deaths in the nonoverloaded
groups as a whole (P less than .03). No weight loss was observed with any
chelator. Significant reductions in hemoglobin and white cell count were
observed with CP20(L1). No histologic abnormalities of kidney, spleen, bone
marrow, or stifle joints were observed. Intracytoplasmic inclusion bodies
were observed in the centrilobular hepatocytes of animals administered each
of the hydroxypyridin-4-ones, while the DFO-treated and control groups
showed no such changes.
Volume 78,
Issue 10,
pp. 2727-2734,
11/15/1991
Copyright © 1991 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. S. Ibrahim, J. E. Edwards Jr, Y. Fu, and B. Spellberg
Deferiprone iron chelation as a novel therapy for experimental mucormycosis
J. Antimicrob. Chemother.,
November 1, 2006;
58(5):
1070 - 1073.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. H. Maclean, J. L. Cleveland, and J. B. Porter
Cellular zinc content is a major determinant of iron chelator-induced apoptosis of thymocytes
Blood,
December 15, 2001;
98(13):
3831 - 3839.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Choudhury, R. O. Epemolu, B. L. Rai, R. C. Hider, and S. Singh
Metabolism and Pharmacokinetics of 1-(2'-Trimethylacetoxyethyl)-2-ethyl-3-hydroxypyridin-4-one (CP117) in the rat
Drug Metab. Dispos.,
March 1, 1997;
25(3):
332 - 339.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. A. Yokel, K. A. Meurer, C. B. Hong, K. M. Dickey, T. L. Skinner, and A. M. Fredenburg
Short-Term Oral 3-Hydroxypyridin-4-one Dosing Increases Aluminum Excretion and Partially Reverses Aluminum-Induced Toxicity in the Rabbit Independent of Chelator Lipophilicity
Drug Metab. Dispos.,
February 1, 1997;
25(2):
182 - 190.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
N. F. Olivieri and G. M. Brittenham
Iron-Chelating Therapy and the Treatment of Thalassemia
Blood,
February 1, 1997;
89(3):
739 - 761.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. F. Olivieri, G. M. Brittenham, D. Matsui, M. Berkovitch, L. M. Blendis, R. G. Cameron, R. A. McClelland, P. P. Liu, D. M. Templeton, and G. Koren
Iron-Chelation Therapy with Oral Deferiprone in Patients with Thalassemia Major
N. Engl. J. Med.,
April 6, 1995;
332(14):
918 - 922.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. G. Nathan
An Orally Active Iron Chelator
N. Engl. J. Med.,
April 6, 1995;
332(14):
953 - 954.
[Full Text]
|
|
|
|
|
|
|
R. Kayyali, J. B. Porter, Z. D. Liu, N. A. Davies, J. H. Nugent, C. E. Cooper, and R. C. Hider
Structure-Function Investigation of the Interaction of 1- and 2-Substituted 3-Hydroxypyridin-4-ones with 5-Lipoxygenase and Ribonucleotide Reductase
J. Biol. Chem.,
December 21, 2001;
276(52):
48814 - 48822.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
