Exercise as an antioxidant: it up-regulates important enzymes for cell adaptations to exercise

Aims. - To assess the role of the reactive oxygen species (ROS) in cell signalling and in the regulation of gene expression. Methods. - Exercise causes oxidative stress only when exhaustive. Strenuous exercise causes oxidation of glutathione, release of cytosolic enzymes, and other signs of cell damage. We have tested this hypothesis by studying the effect of inhibition of ROS production by allopurinol (an inhibitor of xanthine oxidase, a free radical generating enzyme) on cell signalling pathways in marathon runners and in rats submitted to exhaustive exercise by running on a treadmill. Results. - Exercise caused an activation of NF-κB in lymphocytes from marathon runners which was completely prevented by allopurinol. In the rat model exercise caused an activation of MAP kinases in gastrocnemius muscle. This in turn activated the NF-κB pathway and consequently the expression of important enzymes associated with defence against ROS (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when ROS production was prevented by allopurinol. Conclusion. - Thus we report evidence that ROS act as signals in exercise because decreasing their formation prevents activation of important signalling pathways which cause useful adaptations in cells. Because these signals result in an up-regulation of powerful antioxidant enzymes, exercise itself can be considered as an antioxidant.