Oxygen Toxicity in Exercise
Oxygen, as a metabolic fuel, allows an attractive yield of energy-rich phosphates
per unit substrate, and oxidative metabolism avoids the formation of lactic acid
--a significant factor in the development of muscle fatigue during exercise.
Recent advances in free radical biochemistry have made it clear that not all
of the oxygen consumed by live cells is completely (tetravalently) reduced. An
estimated 2-8 percent of the total oxygen consumed may escape from the metabolic
path after being partly reduced. Such incompletely reduced forms of oxygen and
their byproducts, collectively referred to as reactive oxygen species, are
implicated in a wide variety of reactions that may adversely affect our state of
health and longevity. During physical exercise O2 flux through the body is
remarkably enhanced. The rate of oxygen uptake by the body increases by tenfold
to fifteenfold and is accompanied by more than a hundredfold increase in O2 flux
in the active skeletal muscles.
A considerable body of experimental evidence has accumulated in recent years suggesting
that physical exercise, under certain circumstances, induces oxidative stress.1,2
This is an area of critical concern because exercising is not only a
recreational activity but also has well-established therapeutic value. For
patients suffering from disorders that are known to have an oxidative
stress-related etiology, exercise-induced oxidative stress should be treated
with particular concern. For example, oxidative modification of low density
lipoprotein is known to play a major role in the pathogenesis of
atherosclerosis. Recently, Shern et al.3 reported that the susceptibility
of low density lipoprotein to oxidation was higher in exercising humans (n = 22 per group) than in their relatively sedentary counterparts. This suggests that we should consider the exercise-induced oxidative stress factor when designing exercise regimes for such patient groups.
Physical training enhances tissue antioxidant defenses, but such added protection may not be sufficient to defend against oxidative stress during long, strenuous exercise. Habitual physical exercise is a precious therapeutic tool in preventive medicine. A thorough understanding of the complications associated with exercise-induced oxidative stress is necessary for effective handling of this undesired effect. Such knowledge will help in designing exercise and nutrition protocols that will better serve our interests.
Defense Against Oxidative Stress
In biological systems, an imbalance in the pro- and anti-oxidant forces in favor of the former is referred to as oxidative stress. Processing of the one-electron reduction product of molecular oxygen, superoxides, to hydrogen peroxide is catalyzed by the enzyme family superoxide dismutases. Decomposition of tissue hydrogen peroxide can be catalyzed by the enzymes catalase or glutathione peroxidase. Glutathione peroxidase activity requires glutathione as a substrate and selenium as a cofactor. Vitamin E serves as a major lipid phase antioxidant that protects against oxidative lipid damage. Vitamin C, in the absence of free transition metal ions, may serve as an effective antioxidant.
Oxidant-antioxidant interaction involves electron transfer from the antioxidant to the electron-seeking oxygen-free radical. As a result, during such radical neutralization interaction, antioxidants are transformed to an oxidized state that is no longer able to detoxify reactive oxygen. In this situation, it becomes necessary to recycle this oxidized antioxidant to its potent reduced form. In tissues, several antioxidants may act in concert to let such recycling happen. Thus, the strength of antioxidant defense is not dependent on a single antioxidant but on the efficacy with which several antioxidants cooperate to let the antioxidant chain reaction function.2,4