Original Contribution
Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training

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Abstract

Exercise causes oxidative stress only when exhaustive. Strenuous exercise causes oxidation of glutathione, release of cytosolic enzymes, and other signs of cell damage. However, there is increasing evidence that reactive oxygen species (ROS) not only are toxic but also play an important role in cell signaling and in the regulation of gene expression. Xanthine oxidase is involved in the generation of superoxide associated with exhaustive exercise. Allopurinol (an inhibitor of this enzyme) prevents muscle damage after exhaustive exercise, but also modifies cell signaling pathways associated with both moderate and exhaustive exercise in rats and humans. In gastrocnemius muscle from rats, exercise caused an activation of MAP kinases. This in turn activated the NF-κB pathway and consequently the expression of important enzymes associated with defense against ROS (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when ROS production was prevented by allopurinol. Thus ROS act as signals in exercise because decreasing their formation prevents activation of important signaling pathways that cause useful adaptations in cells. Because these signals result in an upregulation of powerful antioxidant enzymes, exercise itself can be considered an antioxidant. We have found that interfering with free radical metabolism with antioxidants may hamper useful adaptations to training.

Section snippets

Free radicals in exhaustive physical exercise

The beneficial effects of regular, nonexhaustive physical exercise have been known for a long time. There is irrefutable evidence of the effectiveness of regular physical activity in the primary and secondary prevention of several chronic diseases (e.g., cardiovascular disease, diabetes, cancer, hypertension, obesity, depression, and osteoporosis) and premature death [1]. However, the beneficial effects of exercise are lost with exhaustion. It is well known that exhaustive exercise (especially

Sources of free radicals in exercise

In setting out to determine the mechanism by which exercise causes an increased production of ROS, we came across the generally accepted idea that, because exercise causes an increase in oxygen consumption by mitochondria, it also causes an increase in free radical formation by these organelles. This, however, is based on the misconception that the proportion of ROS formed by mitochondria is in the range of 2% of the total oxygen consumed. Very early work by the group of Britton Chance [15]

Role of free radicals in muscle adaptation to exercise

The idea of the deleterious effects of free radicals has been firmly entrenched in the minds of scientists for the past 30 years. However, there is now an appreciation that the reactive oxygen species generated during muscle contraction have a physiological role in the adaptation to exercise. In response to the free radical assault, the cell has developed a number of antioxidant defense systems such as superoxide dismutase, the peroxidases, the glutathione redox cycle with its associated

Exercise and antioxidants

As described above ROS produced in exercise act as signals that regulate molecular events important in muscle cell adaptations to exercise. The practical consequence is that antioxidant administration prevents such adaptations and, thus, the recommendation of taking antioxidant supplements before moderate exercise should be revised as they may prevent useful adaptations induced by exercise. In 1993 Michael Reid and co-workers [10] showed that in unfatigued skeletal muscle ROS have a positive

Concluding remarks

These findings clearly indicate that ROS generated during exercise act as signals to increase the production of enzymes relevant to the adaptation of muscle cells to exercise. Moreover, these findings lead us to reconsider the “wisdom” of taking antioxidant supplements during training. In all likelihood, antioxidant supplements should not be recommended before training as they interfere with muscle cell adaptation. Indeed, when rats were trained, the expression of antioxidant enzymes and of

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