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Mechanisms and Biomarkers (WG 4) page 7
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Chapter 1. The Chemistry of Oxidative Stress and its Pathophysiological Consequences
INTRODUCTION
This chapter introduces the concept of oxidative stress, a phenomenon universal to all higher
organisms that have evolved to use oxygen as a respiratory substrate. Oxygen, like iron
(Bilton, 2000) presents a unique contradiction in its role in aerobic life forms, where it is as
fully essential to life as it is highly toxic in the absence of adequate antioxidant protection.
An overview of scientific advances accumulated since 1986 is presented, corresponding to the
discovery of superoxide dismutase, to the present. This should help the reader to have
milestones on oxidative stress through the concepts defined in it including, free radicals,
antioxidants, and their role in the physiology; but also to introduce the analytical
methodologies used to identify and quantitate this type of stress.
Oxidative stress : basic concepts
It is important to realise that oxidative stress is an imbalance occurring when the deleterious
effects of oxygen metabolites overwhelm the array of body defences. In the following a
review will be developed on the metabolism of oxygen, the resulting reactive species, the
mechanisms involved in the interactions with biological molecules, the defence systems to
neutralise the reactive species and the ways used to measure these processes.
Oxygen chemistry and metabolism
Oxidative stress mainly involves oxygen which is essential for aerobic living organisms. The
chemistry of oxygen molecules already indicates a particular distribution of electrons in the
external orbital making this molecule unique from the others found in the biosphere. Indeed,
the usual electron coupling necessary to stabilise a given molecule does not occur and the
stable oxygen molecule possesses two unpaired electrons which render them reactive
(Balentine, 1982). This chemical instability may lead to the formation of the reactive oxygen
molecule: singlet oxygen generated by absorption of energy (22 kcal from the ground state).
On the other hand, other reactions which can be expected from the chemical unstability of
oxygen molecule are: i) an intrinsic pairing of these electrons leading to a triplet state, ii) a
stabilisation by an external electron transforming oxygen molecule into superoxide anion and
iii) a second addition of an electron resulting in the formation of peroxide anion (Halliwell,
1993). All the resulting products are known to be chemically very active. Oxygen is also an