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Mechanisms and Biomarkers (WG 4) page 9
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hazardous for the organisms such as hydroxyl radical, hydroperoxyl radical, hydrogen
peroxide, nitric oxide or peroxynitrite (Rice-Evans et al., 1994).
The most aggressive free radical is the hydroxyl radical (HO°) because of its reaction with a
diffusion-controlled rate with almost every molecule in the living cell. Even though its
diffusion is limited to 5-10 molecular diameters, the second-order rate constants is so high
(10 9 -10 10 M -1 s -1 ) that every molecule encountered will be attacked. Hydroxyl radicals are
generated by three main mechanisms :
-homolytic fission of water molecules by ionising radiation: ultraviolet, X- and δ-rays,
microwave (von Sonntag, 1987).
-reaction of transition metals ions with hydrogen peroxide illustrated by the Fenton reaction
occurring with iron and efficiently increased by the presence of ascorbate. It can be noticed
that superoxide anion is involved in reduction of ferric ion into ferrous ion which then reacts
with hydrogen peroxide to generate hydroxyl radical, these reactions are described as Haber-
Weiss reaction (Halliwell and Gutteridge, 1990a). In contrast with some pathological
conditions such as inflammation and ischemia-reperfusion, transition metals such as iron and
copper are not freely available for such a reaction since they are bound to proteins including
caeruloplasmin or ferritin (Halliwell and Gutteridge, 1990b).
- Hydroxyl radicals may also be formed during homolytic scission of peroxynitrous acid
ONOOH (Pryor and Squadrito, 1995) in the complete absence of metal transition ions, but
current opinion tends to favour other mechanisms to explain the reactivity of ONOOH, which
has a reduction potential of 2.1 vs 2.3 for ·OH/H2O.
The hydroperoxyl radical (HOO°) level under physiological condition is low because of the
low pKa of 4.5 of that reaction. However in pathological conditions when the pH decreases
(ischemia, acidosis) or at the proximity of the inner mitochondrial membrane its production
may be increased. Even though little evidence has been shown towards its action in vivo, the
reactivity can be supposed higher than superoxide anion because of its lipophilicity that
render it able to cross and oxidise the membrane lipids and to reach the intracellular
compartment (Halliwell and Gutteridge. 1986).
The hydrogen peroxide (H2O2) is a non radical oxygen species resulting from divalent
reduction of superoxide anion. This reaction can be spontaneous as this species can be
detected in water at concentrations of 10 -5 -10 -8 mol/L and in the body its generation is
catalysed by oxidases (amine- or urate-oxidases) and more specifically by the superoxide
dismutase (see below). Besides of oxidant activity, hydrogen peroxide may also have