Handbook of Vitamin C Research

Impact of Vitamin C on Exercise-Induced Oxidative Stress 13ProteinProteins are major targets for RONS because of their high overall abundance inbiological systems and it has been estimated that proteins interact with the majority (50-75%)of radical species generated [77]. Oxidative damage to proteins can occur directly byinteraction of the protein with a radical species or indirectly by interaction of the protein witha secondary product (resulting from interaction of radical with lipid or sugar molecule) [28].Modifications of a proteins under conditions of oxidative stress can occur via peptidebackbone cleavage, cross-linking, and/or modification of the side chain of virtually everyamino acid. Moreover, most protein damage is irreparable and oxidative modification of theprotein structure can lead to loss of enzymatic, contractile, or structural function in theaffected proteins, thus making them increasingly susceptible to proteolytic degradation [78].The formation and accumulation of protein carbonyls (PC) is one of the most commonly usedmethods for assessing overall protein oxidation.DNAPotential oxidative damage to DNA by free radicals can occur in a variety of ways,including: modification of all bases, production of base-free sites, base deletions, frameshifts, strand breaks, DNA-protein cross-links, and chromosomal rearrangement [79].Hydroxyl radical is considered one of the primary radicals involved in DNA damage, as itpossesses the ability to react with all components of the DNA molecule. This formation ofhydroxyl radical in close proximity to the DNA molecule, likely occurs via the Fentonreaction, as hydrogen peroxide (produced via the dismutation of superoxide) passes throughthe nuclear membrane and comes into contact with transition metals (likely copper bound toDNA chromosomes), thus generating the highly reactive hydroxyl radical [80].DNA subjected to attack by radical species results in the formation of a variety of baseand sugar modification products. The presence of these modified products is used to indicateoxidative stress, as they are not present during normal nucleotide metabolism. Theseproducts can be measured via HPLC, HPLC-CL, GC-MS, and antibody-based techniques[79]. Typically the product, 8-hydroxy-2-deoxyguanosine (8-OHdG) is measured as an indexof oxidative damage to DNA. Levels of 8-OHdG can be assessed in muscle and organ tissue,as well as in serum, urine and isolated leukocytes. 8-OHdG has been shown to inducemutation, is found frequently in tumor-related genes, and has been correlated to the incidenceof some cancers [81].Antioxidant CapacityThe body‘s antioxidant capacity (AOC) serves to protect the cells from excess RONSproduction. The AOC is comprised of both endogenous (bilirubin, uric acid, superoxidedismutases, catalase, glutathione peroxidase etc.) and exogenous (carotenoids, tocopherols,vitamin C, bioflavonoids, etc.) compounds [21]. In response to conditions of oxidative stress