measure physical fitness is based on the ability of
an individual to utilize atmospheric oxygen in a
given interval of time per kilogram of body
weight, i.e. the aerobic capacity. Therefore, ath-
letes aim to boost their aerobic capacity to the
highest possible limit. Supply of more and more
oxygen to active tissues fuels oxidative metabo-
lism that produces higher amounts, compared
with anaerobic metabolism, of energy-rich phos-
phates and avoids the formation of lactate during
the energy supply process. Physical exercise may
be associated with a 10–20-fold increase in whole
body oxygen uptake (Åstrand & Rodahl 1986).
Oxygen flux in the active peripheral skeletal
muscle fibres may increase by as much as
100–200-fold during exercise (Keul et al. 1972).
Does this markedly enhanced consumption of
oxygen by the tissue at exercise contribute to
oxidative stress? This question was first
addressed in 1978 when it was observed that
strenuous physical exercise indeed induced
oxidative damage to lipids in various tissues
(Dillard et al. 1978). One of the early studies
which kindled a strong motivation for further
research in the area of exercise and oxygen toxic-
ity was reported by Davies et al. (1982). Using the
electron paramagnetic or spin resonance (EPR or
ESR) spectroscopy for the direct detection of free
radical species in tissues, it was shown that
exhaustive exercise results in a two- to threefold
increase in free radical concentrations of the
muscle and liver of rats exercised on a treadmill.
Since then, a considerable body of research has
accumulated showing that strenuous physical
exercise may be associated with oxidative stress
(Senet al. 1994c).Possible mechanisms
During exercise, several mechanisms may con-
tribute to the generation of excess ROS. Some of
the possibilities are listed below.Electron transport chain
Boveriset al. (1972) showed that mitochondria
can generate H 2 O 2. Exercise training increases
electron flux capacity of skeletal muscle mito-
chondria, and this effect is known to be a mecha-
nism by which aerobic capacity of trained
muscles is increased (Robinson et al. 1994). It is
likely that the exercise-associated increased elec-
tron flux in the mitochondria may result in
enhanced ‘leak’ of partially reduced forms of
oxygen centred radicals.Ischaemia reperfusion
During exercise, blood is shunted away from
several organs and tissues (e.g. kidneys, splanch-oxidative stress and antioxidant nutrients 293
Table 22.1Rat liver enzymes that may contribute to the generation of reactive oxygen species. From Sies (1974).
Enzyme EC LocalizationGlycolate oxidase 1.1.3.1 Peroxisome
l-a-hydroxyacid oxidase 1.1.3a Peroxisome
l-gulonolactone oxidase 1.1.3.8 Cytosol
Aldehyde oxidase 1.2.3.1 Cytosol
Xanthine oxidase 1.2.3.2 Cytosol
d-amino-acid oxidase 1.4.3.3 Peroxisome
Monoamine oxidase 1.4.3.4 Mitochondrial outer membrane
Pyridoxamine oxidase 1.4.3.5 Endoplasmic reticulum
Diamine oxidase 1.4.3.6 Endoplasmic reticulum
NADPH-cytochrome creductase 1.6.99.1 Endoplasmic reticulum
NADPH-cytochrome creductase 1.6.99.3 Peroxisome core
Urate oxidase 1.7.3.3 Peroxisome core
Superoxide dismutase 1.15.1.1 Cytosol and mitochondrial matrix