Introduction
‘Diradical’ molecular oxygen has a strong affin-
ity for four more electrons. Under normal resting
conditions, approximately 95% of all oxygen
consumed by the mammalian cells is reduced via
the mitochondrial cytochrome oxidase to yield
two molecules of water and energy. The remain-
ing 3–5% of oxygen consumed at rest can be
utilized in an alternative univalent pathway for
the reduction of oxygen, and reactive oxygen
species (ROS) are thus produced (Singal &
Kirshenbaum 1990). Formation of superoxides
and hydrogen peroxide can be regulated by
either enzymatic or non-enzymatic mechanisms,
whereas no enzymes are required for the forma-
tion of hydroxyl radical. Hydroxyl radical is
highly reactive and may be formed either
through a iron-catalysed Fenton reaction (Fe^2 ++
H 2 O 2 Æ Fe^3 ++ OH–+HO•) or through the
Haber–Weiss reaction (O 2 •–+H 2 O 2 +Fe^2 +ÆO 2 +
OH–+HO•+Fe^3 +).
Partial reduction of oxygen, an event primarily
underlying the generation of ROS, has been
shown to be catalysed by a number of enzymes
of rat liver. Some of the enzymes responsible for
the generation of hydrogen peroxide or superox-
ide anion radical are listed in Table 22.1. Boveris
et al. (1972) have shown that mitochondria,
microsomes, peroxisomes and cytosolic enzymes
are effective H 2 O 2 generators, contributing in the
rat liver, respectively, 15%, 45%, 35% and 5% to
the cytosolic H 2 O 2 at a Po 2 of 158 mmHg when
fully supplemented by their substrates. Bio-
transformation of xenobiotics (e.g. pollutants
and drugs), especially via cytochrome P 450 -
dependent mechanisms, may also contribute
to the generation of reactive oxygen species
(Archakov & Bachmanova 1990; Roy &
Hanninen 1993).
Oxidative stress is now known to be impli-
cated in the pathogenesis of a wide variety of
health disorders, including coronary heart dis-
eases, cerebrovascular diseases, emphysema,
bronchitis, chronic obstructive lung disease,
some forms of cancer, diabetes, skeletal muscular
dystrophy, infertility, cataractogenesis, dermati-
tis, rheumatoid arthritis, AIDS-related dysfunc-
tions, and Alzheimer’s and Parkinson’s diseases
(Sen & Hanninen 1994; Davies & Ursini 1995). In
addition, reactive oxygen species are thought to
critically contribute to ageing and age-related
disorders (Levine & Stadtman 1996). A late-
breaking aspect of ROS action that has drawn the
attention of current biomedical research is the
ability of these reactive species to modulate a
number of intracellular signal transduction
processes that are critically linked to widespread
pathologies such as cancer, human immuno-
deficiency virus replication and atherosclerosis.
ROS, at a concentration much below that
required to cause oxidative damage to biological
structures, can act on highly specific molecular
loci inside the cell (Sen & Packer 1996).Exercise-induced oxidative stress
In exercise physiology, a common approach to