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Transition Metals and Free Radicals
In our last newsletter we spoke in general about the fact
that ionic transition metals can produce huge amounts of
free radical.
In
this newsletter we will let other researchers talk about
their findings. Please be aware that research into 'metal
mediated Fenton reactions' is still quite new and yet there
already is a large amount of solid scientific evidence.
Article
written by Masato Asanuma, Norio Ogawa (1) Dept. of Neurosci..
Okayama Univ. Med. Sch. - Okayama . Japan (2) Department
of Neuroscience, Inst. of Molecular & Cellular
Medicine. Okayama University Medical School - Okayama . Japan
http://www.uclm.es/inabis2000/symposia/files/154/
Effects of different transition metals on free radical
generation and peroxide reaction in the brain: Modification
by dopamine-related compounds.
In
order to clarify effects of different transition metals
on free radical generation and lipid and protein peroxide
reaction in the brain, we measured .OH generation induced
by metal ions, Fe(II), Fe(III) and Cu(II) ions with/ without
hydrogen peroxide (H 2 O 2 ) by an electron spin resonance
spectrometry, and also evaluated these metal-induced changes
in auto-oxidized lipid peroxides, as thiobarbituric acid-reactive
substances (TBARS), and carbonyl contents in oxidatively
modified proteins (OMP) in the brain tissue. These transition
metals-induced neuronal cell damage was also assessed using
neuronal cultured cells. We also examined the effects of
dopamine (DA) or L-dopa on transition metal-induced free
radical generation and lipid peroxidation in the brain.
Cu(II) ion showed greater generation of .OH radicals than
Fe(II) and Fe(III) ions with or without H 2 O 2 . Ceruloplasmin
inhibited Cu(II)-induced .OH generation with or without
H 2 O 2 . Both Fe(II) and Fe(III) ions markedly increased
TBARS production and carbonyl contents of OMP by auto-oxidation
of brain tissue. We could clearly demonstrated that Fe
ions-induced enhancement of lipid and protein peroxide
reactions was correlated to their .OH generating effects,
but Cu(II) ion had no effects on TBARS nor OMP. These metal
ions dose-dependently reduced cell viability of cultured
neuronal cells (Cu(II)>>Fe ions). Taken together
these findings, Fe(II) and Fe(III) ions-induced neurotoxicity
is thought to be mainly caused by their .OH generating
effects, via .OH-induced lipid peroxidation, protein oxidation
and/or DNA damage. Our resulting data concerning to Cu(II)
ion also indicate that abundant Cu-binding molecules which
can trap Cu(II) ions might protect Cu(II)-induced .OH generation
and consequent lipid and protein peroxidation in the normal
condition. DA and L-dopa inhibited both .OH generation
and lipid peroxidation of the brain tissue induced by Fe(II),
Fe(III) and Cu(II) ions, especially in the presence of
H 2 O 2 . These inhibiting effects of DA and L-dopa on
metal ions-induced .OH generation with H 2 O 2 might be
due to metal-chelating property of both catechols to finally
form melanin under the oxidative condition. Since neuromelanin
have protective effcts on metal-induced lipid peroxidation,
these findings indicate that neuromelanin which is the
end product of DA or L-dopa oxidation might exert anti-oxidant
function to protect neurodegeneration.
The
next articles are taken from the 'Medline'
database.
Metal ions catalytic for free radical reactions in the plasma
of patients with fulminant hepatic failure.
Author Evans PJ; Evans RW; Bomford A; Williams R; Halliwell B Address Pharmacology Group, University of London King's College
, UK . Source Free Radic Res, 1994 Mar, 20:3, 139-44
Abstract
We propose that the frequency and severity of multi-organ
failure (MOF) in fulminant hepatic failure (FHF) involves
free radical damage caused by the presence of circulating
iron and copper ions, catalytic for free radical reactions.
The presence of such metal ions is demonstrated by using
the sensitive bleomycin and phenanthroline assays. Antioxidant
therapy, e.g., using chelating agents that prevent metal
ions from stimulating free radical reactions, may have benefit
in the treatment of FHF and its consequences.
Language of Publication English Unique Identifier 94290593
Transition
metals as catalysts of "autoxidation" reactions.
Author Miller DM; Buettner GR; Aust SD Address Department of Chemistry and Biochemistry, Utah State University
, Logan 84322-0300. Source Free Radic Biol Med, 1990, 8:1, 95-108
Abstract
Superoxide
(O2-), hydrogen peroxide (H2O2), and hydroxyl radical (.OH)
produced from the "autoxidation" of
biomolecules, such as ascorbate, catecholamines, or thiols,
have been implicated in numerous toxicities. However, the
direct reaction of dioxygen with the vast majority of biomolecules,
including those listed above, is spin forbidden, a condition
which imposes a severe kinetic limitation on this reaction
pathway. Therefore, an alternate mechanism must be invoked
to explain the "autoxidations" reactions frequently
reported. Transition metals are efficient catalysts of redox
reactions and their reactions with dioxygen are not spin
restricted. Therefore it is likely that the "autoxidation" observed
for many biomolecules is, in fact, metal catalyzed. In this
paper we discuss: 1) the quantum mechanic, thermodynamic,
and kinetic aspects of the reactions of dioxygen with biomolecules;
2) the involvement of transition metals in biomolecule oxidation;
and 3) the biological implications of metal catalyzed oxidations.
We hypothesize that true autoxidation of biomolecules does
not occur in biological systems, instead the "autoxidation" of
biomolecules is the result of transition metals bound by
the biomolecules.
Language of Publication English Unique Identifier 90215326
Amyloid precursor protein, copper and Alzheimer's disease.
Author Multhaup G Address ZMBH Center for Molecular Biology, University of Heidelberg
, Germany . Source Biomed Pharmacother, 1997, 51:3, 105-11
Abstract
Although a consensus that Alzheimer's disease (AD) is a
single disease has not yet been reached, the involvement
of the amyloid precursor protein (APP) and beta A4 (A beta)
in the pathologic changes advances our understanding of the
underlying molecular alterations. Increasing evidence implicates
oxidative stress in the neurodegenerative process of AD.
This hypothesis is based on the toxicity of beta A4 in cell
cultures, and the findings that aggregation of beta A4 can
be induced by metal-catalyzed oxidation and that free oxygen
radicals might be involved in APP metabolism. Another neurological
disorder, familial amyotrophic lateral sclerosis (FALS),
supports our view that AD and FALS might be linked through
a common mechanism. In FALS, SOD-Cu(I) complexes are affected
by hydrogen peroxide and free radicals are produced. In AD,
the reduction of Cu(II) to Cu(I) by APP involves an electron-transfer
reaction and could also lead to a production of hydroxyl
radicals. Thus, copper-mediated toxicity of APP-Cu(II)/(I)
complexes may contribute to neurodegeneration in AD.
Language of Publication English Unique Identifier 97324976
We have selected these articles or their abstracts from
easily accessible internet sites. There are hundreds of articles
available for those who really want to study the problem
of metal mediated Fenton reactions and the involvement of
ionic transition metals.
The
IHMT is a simple tool to give us an indication of the
amount of ionic metals present in our environment and our
own body.
Hans, 19.10.2005
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The science and philosophy of
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