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1 Catholic University of Valencia, Spain
2 Department of Physiology, University of Valencia, School of Medicine, Spain
3 Department of Kinesiology and Nutritional Sciences, University of Wisconsin-Madison, USA
Reactive oxygen or nitrogen species (RONS) are produced during exercise due, at least in part, to the activation of xanthine oxidase. When exercise is exhaustive they cause tissue damage; however, they may also act as signals inducing specific cellular adaptations to exercise. We have tested this hypothesis by studying the effects of allopurinol-induced inhibition of RONS production on cell signalling pathways in rats submitted to exhaustive exercise. Exercise caused an activation of mitogen-activated protein kinases (MAPKs: p38, ERK 1 and ERK 2), which in turn activated nuclear factor 
B (NF-B) in rat gastrocnemius muscle. This up-regulated the expression of important enzymes associated with cell defence (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when RONS production was prevented by allopurinol. Thus we report, for the first time, evidence that decreasing RONS formation prevents activation of important signalling pathways, predominantly the MAPK–NF-B pathway; consequently the practice of taking antioxidants before exercise may have to be re-evaluated.
(Received 3 December 2004;
accepted after revision 26 May 2005;
first published online 2 June 2005)
Corresponding author J. Viña: Department of Physiology, Faculty of Medicine, Blasco Ibañez 15, 46010 Valencia, Spain. Email: jose.vina{at}uv.es
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