Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation
and attenuates rhabdomyolysis-induced renal failure
Olivier Boutauda,1,2, Kevin P. Mooreb,1, Brandon J. Reederc,
David Harryb, Alexander J. Howieb, Shuhe Wanga, Clare K. Carneyd,
Tina S. Mastersona, Taneem Amina, David W. Wrightd, Michael T.
Wilsonc,
John A. Oatesa,e, and L. Jackson Roberts IIa,e
+ Author Affiliations
Departments of aPharmacology,
eMedicine, and
dChemistry, Vanderbilt University, Nashville, TN 37232;
cDepartment of Biological Sciences, University of Essex,
Colchester, Essex CO4 3SQ, United Kingdom; and
bDepartments of Medicine and Pathology,
University College London Medical School,
London NW3 2QG, United Kingdom
Edited* by Garret A. FitzGerald,
University of Pennsylvania,
Philadelphia, PA, and accepted by the Editorial Board January 4, 2010
(received for review September 9, 2009)
↵1O.B. and K.P.M. contributed equally to this work.
Abstract
Hemoproteins, hemoglobin and myoglobin, once released from
cells can cause severe oxidative damage as a consequence of
heme redox cycling between ferric and ferryl states that
generates radical species that induce lipid peroxidation.
We demonstrate in vitro that acetaminophen inhibits
hemoprotein-induced lipid peroxidation by reducing ferryl heme
to its ferric state and quenching globin radicals.
Severe muscle injury (rhabdomyolysis) is accompanied by the
release of myoglobin that becomes deposited in the kidney,
causing renal injury.
We previously showed in a rat model of rhabdomyolysis that
redox cycling between ferric and ferryl myoglobin yields
radical species that cause severe oxidative damage to the
kidney.
In this model, acetaminophen at therapeutic plasma concentrations
significantly decreased oxidant injury in the kidney, improved
renal function, and reduced renal damage.
These findings also provide a hypothesis for potential therapeutic
applications for acetaminophen in diseases involving hemoprotein-
mediated oxidative injury.
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http://www.patentstorm.us/patents/6509380/description.html US Patent 6509380 - Method of treating iron overload with
acetaminophen
US Patent Issued on January 21, 2003
Estimated Patent Expiration Date: December 14, 2021Estimated
Expiration Date is calculated based on simple USPTO term provisions.
It does not account for terminal disclaimers, term adjustments,
failure to pay maintenance fees, or other factors which might affect
the term of a patent.
Abstract Claims Description Full Text
FIELD OF THE INVENTION
The present invention relates to methods for reducing iron levels
and/ or levels of other toxic metals or elements in mammals.
In a particular aspect, the present invention relates to methods for
reducing free iron ion levels and/or excess and toxic levels of other
elements in mammals, and to the removal of excess iron or excesses
of other metals/elements stored in the organs by administration of
acetaminophen and/or structural or chemical analogues or derivatives
thereof.
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