Handbook of Vitamin C Research

Impact of Vitamin C on Exercise-Induced Oxidative Stress 11Secondary SourcesIn addition to the primary production of RONS discussed above, in cases of exhaustive,eccentric, or prolonged exercise, secondary RONS generation can occur by way of increasedmigration of neutrophils and other phagocytic cells as a component of the immune responsefollowing tissue injury [53]. This phenomenon is referred to as respiratory burst and isprimarily mediated by NADPH oxidase bound to the plasma membrane of invadingphagocytic cells. In this respect, the reduction of oxygen to form the superoxide radical iscatalyzed by oxidizing the reduced form of nicotinamide adenine dinucleotide phosphate(NADPH), resulting in the formation of NADP + [59].Recall from above that the production of hydroxyl radical is favored in the presence offree transition metals (e.g., iron, copper). For this reason, the body possesses extensive metalsequestering proteins in an effort to prevent the deleterious effects of their unbound (i.e.,―free‖) circulation [12]. However, mechanical trauma and/or acidosis induced during intenseexercise can result in the destruction of iron containing proteins (e.g., erythrocytes,myoglobin), as well as the release of iron from transferrin, in turn promoting the formation ofRONS via metal catalyzed reactions [73].In the above ways, acute exercise possesses the ability to serve as a powerful RONSgenerating stimulus. This increased production of RONS may occur from either theincreased consumption of oxygen, as well as from a multitude of other primary or secondarymechanisms. At present, increased RONS production appears to occur in response to bothaerobic and anaerobic exercise; however the precise source of generation remains to becompletely elucidated. It is likely that the increase in RONS observed during and followingexercise results from a combination of the above pathways, which all collectively result in theincreased presence of oxidized biomolecules.Specific Cellular Damage Induced via RONSReactive oxygen/nitrogen species can react with lipids, proteins, and DNA to producestable biomarkers, which can then be measured and analyzed to yield an indication of theoverall oxidative stress experienced by the system. Precise cellular damage resulting fromRONS is related specifically to which macromolecules are being targeted by the oxidants, thefrequency and duration of attack, as well as the tissue specific antioxidant defenses present.Methods of Assessing RONS Formation and Tissue InjuryDue to the high reactivity and relatively short half lives of radical species (e.g., 10 -5 , 10 -9seconds for superoxide radical and hydroxyl radical, respectively), direct measurement isextremely difficult to employ. However, direct assessment of free radical production ispossible via electron spin resonance spectroscopy (ESR) involving spin traps, as well as twoother less common techniques such as radiolysis and laser flash photolysis [74]. ESR worksby recording the energy changes that occur as unpaired electrons align in response to a