Handbook of Vitamin C Research

156Borut Poljsak and John G. IonescuBasic intracellular reaction in which ascorbic acid and ROS are involved (McKersie1996):2O 2-˙+ 2H + + ascorbate2 H 2 O 2 + dehydroascorbate˙H 2 O 2 + 2 ascorbate2H 2 O + 2 monodehydroascorbate˙The indirect role of the ascorbate as an antioxidant is to regenerate membrane-boundantioxidants, such as alpha-tocopherol that scavenge peroxyl radicals and singlet oxygen,respectively:Tocopheroxyl radical + ascorbatetocopherol + monodehydroascorbateThe above reactions indicate that there are two different products of ascorbate oxidation:monodehydroascorbate and dehydroascorbate which represent one and two electron transfers,respectively. The monodehydroascorbate can either dismutate spontaneously, or is reduced toascorbate by NAD(P)H monodehydroascorbate reductase:2 monodehydroascorbate ascorbate + dehydroascorbatemonodehydroascorbate + NAD(P)Hascorbate + NAD(P)The dehydroascorbate is unstable at pH greater than 6 and decomposes to tartrate andoxalate (McKersie 1996). To prevent this, dehydroascorbate is rapidly reduced to ascorbateby dehydroascorbate reductase, using reducing equivalents from glutathione:2 GSH + dehydroascorbate GSSG + ascorbate (Figure 1)In vitro tests performed under physiological conditions show a better viability of ascorbicacid pretreated cells, which might be the consequence of ascorbic acid prevention of oxidantinducedapoptosis (Deutsch 1998). In the absence of added metal ions, however, vitamin Cinhibits the formation of 8-oxodG in purified DNA exposed to peroxynitrite or UV light (Huand Shih 1997¸ Fiala et al. 1996). Also the study of Panayiotidis et al. (1997) has shownreduced strand breakage, as determined by the comet assay in lymphocytes .Results ofcytotoxicity tests in S. cerevisiae cells pretreated with ascorbic acid and subsequently treatedwith Cr(VI) indicate a preventive effect of ascorbic acid (Poljsak et al. 2005) regardingintracellular oxidation. These results are in agreement with those of Blankenship et al. (1997)on CHO cells.When sufficient exogenous iron (as ferrous ammonium sulfate) is added to plasma tosaturate transferrin and result in nonprotein-bound, bleomycin- detectable iron (BDI),endogenous and exogenous vitamin C inhibits rather than promotes lipid peroxidation(Berger et al. 1997).