Handbook of Vitamin C Research

18Kelsey H. Fisher-Wellman and Richard J. BloomerIn brief, exercise-induced RONS appear to serve as the ―signal‖ needed for the activationof MAPKs (p38 and ERK1/ERK2), which in turn activate the redox sensitive transcriptionfactor NF-κB [103], via activation of IκB kinase, which then phosphorylates IκB (theinhibitoy subunit of NF-κB). IκB is then ubiquinated and subsequently degraded via thecytosolic ubiquitin-proteosome pathway, thereby releasing NF-κB to migrate into thenucleus. Several antioxidant enzymes [manganese superoxide dismutase (MnSOD), induciblenitric oxide synthetase (iNOS), glumatylcysteine synthetase (GCS)] contain NF-κB bindingsites in their gene promoter region and thus are potential targets for exercise-inducedupregulation via the NF-κB signaling pathway [29]. These findings support the idea above ofan optimal level of RONS production and suggest that complete elimination of exerciseinducedRONS would not be conducive to optimal physiological function.In summary, oxidative stress is a condition characterized by free radical mediateddamage to various biological molecules. The critical importance of further research andunderstanding in the area is illustrated by the implication of oxidative stress in thepathogenesis of a myriad of acute and chronic human illnesses/diseases. Therefore, furtheridentification of situations in which increased radical species production is promoted, as wellas additional methods to combat such a stress (either nutritional, pharmacological, or lifestyleimplementation) is essential.At present, it appears that any condition in which the consumption of molecular oxygenis increased has the potential to result in an acute state of oxidative stress. One suchcondition is the performance of physical exercise, and exercise-induced oxidative stress isbelieved to play a role in reducing performance and accelerating fatigue and muscle injuryfollowing exercise. However, at present no cause and effect data are available. In fact, asmall amount of oxidative stress may serve as a necessary stimulus for an upregulation in theantioxidant defense system, thereby enhancing protection against future oxidative attacks.Thus, whether exercise-induced RONS should be viewed as a detriment or benefit to physicalperformance/physiological function that should be attenuated and/or utilized remains a topicof debate. The following section will specifically address the current research pertaining toacute exercise, oxidative stress and tissue injury. Specific attention is given to the ability ofvitamin C to attenuate such a stress, as well as the potential consequences of suchattenuation.Exercise-Induced Oxidative Stressand Tissue InjurySince the initial reporting by Dillard and colleagues [104] of an increase in expiredpentane following acute aerobic exercise, coupled with the direct measurement of free radicalproduction following treadmill running in rats by Davies et al. [105], numerous (>300)investigations have been conducted within the field of oxidative stress and exercise. Basedon research conducted over the past 30 years it appears that acute exercise of sufficientvolume and intensity results in the increased production of RONS, in turn promotingtransient conditions of oxidative stress. Evidence for this is provided by investigations notingan increase in various oxidative stress biomarkers following both acute aerobic and anaerobic