Thalassemia Patients and Friends
Discussion Forums => Iron Chelation Corner => Topic started by: ironjustice on November 28, 2011, 03:10:24 AM
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"Minocycline chelated iron"
"Its activity exceeded that of deferoxamine"
Minocycline-Induced Attenuation of Iron Overload and Brain Injury
After Experimental Intracerebral Hemorrhage
Fan Zhao, MD; Ya Hua, MD; Yangdong He, MD; Richard F. Keep, PhD;
Guohua Xi, MD
From the Department of Neurosurgery, University of Michigan,
Ann Arbor, MI.
Correspondence to Guohua Xi, MD, R5018 Biomedical Science, Research
Building, University of Michigan, 109 Zina Pitcher Place, Ann Arbor,
MI 48109-2200. E-mail guohu...@umich.edu
Abstract
Background and Purpose—
Brain iron overload plays a detrimental role in
brain injury after intracerebral hemorrhage (ICH).
A recent study found that minocycline acts as an iron chelator
and reduces iron- induced neuronal death in vitro.
The present study investigated if minocycline reduces iron overload
after ICH and iron-induced brain injury in vivo.
Methods—This study was divided into 4 parts: (1) rats with different
sizes of ICH were euthanized 3 days later for serum total iron and
brain edema determination; (2) rats had an ICH treated with
minocycline or vehicle. Serum iron, brain iron, and brain iron
handling proteins were measured; (3) rats had an intracaudate
injection of saline, iron, iron+minocycline, or iron+macrophage/
microglia inhibitory factor and were used for brain edema and
neuronal death measurements; and (4) rats had an intracaudate
injection of iron and were treated with minocycline.
The brains were used for edema measurement.
Results—After ICH, serum total iron and brain nonheme iron increased
and these changes were reduced by minocycline treatment. Minocycline
also reduced ICH-induced upregulation of brain iron handling proteins
and neuronal death. Intracaudate injection of iron caused brain
edema, blood–brain barrier leakage, and brain cell death, all of which were
significantly reduced by coinjection with minocycline.
Conclusions—The current study found that minocycline reduces iron
overload after ICH and iron-induced brain injury. It is also well
known minocycline is an inhibitor of microglial activation.
Minocycline may be very useful for patients with ICH because both
iron accumulation and microglia activation contribute to brain damage
after ICH.
Key Words:brain edemacerebral hemorrhageironminocyclineReceived April
20, 2011.
Revision received July 8, 2011.
Accepted July 27, 2011.
© 2011 American Heart Association, Inc.
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Minocycline Attenuates Iron Neurotoxicity in Cortical Cell Cultures
Biochemical and Biophysical Research Communications
Jing Chen-Roetlinga, Lifen Chena and Raymond F. Regan, a,
aDepartment of Emergency Medicine Thomas Jefferson University
1020 Sansom Street, Thompson Building Room 239 Philadelphia, PA 19107
Received 4 June 2009. Available online 10 June 2009.
Abstract
Iron neurotoxicity may contribute to the pathogenesis of
intracerebral hemorrhage (ICH).
The tetracycline derivative minocycline is protective in ICH
models, due putatively to inhibition of microglial activation.
Although minocycline also chelates iron, its effect on iron
neurotoxicity has not been reported, and was examined in
this study.
Cortical cultures treated with 10 ìM ferrous sulfate for 24h
sustained loss of most neurons and an increase in
malondialdehyde.
Minocycline prevented this injury, with near-complete
protection at 30 ìM.
Two other inhibitors of microglial activation, doxycycline
and macrophage/microglia inhibitory factor, were ineffective.
Oxidation of isolated culture membranes by iron was also
inhibited by minocycline.
Consistent with prior observations, minocycline chelated iron
in a siderophore colorometric assay; at concentrations less
than 100 ìM, its activity exceeded that of deferoxamine.
These results suggest that attenuation of iron neurotoxicity
may contribute to the beneficial effect of minocycline in
hemorrhagic stroke and other CNS injury models.
Keywords: cell culture; free radical; hemoglobin toxicity;
inflammation; intracerebral hemorrhage; mouse; oxidative
stress; stroke
doi:10.1016/j.bbrc.2009.06.026
Copyright © 2009 Published by Elsevier Inc.