Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/18/2006
Publication Date: 5/25/2006
Citation: Premkumar, K., Min, K., Alkan, Z., Hawkes, W.C., Ebeler, S., Bowlus, C.L. 2006. POTENTIATING AND PROTECTIVE EFFECTS OF ASCORBATE ON OXIDATIVE STRESS DEPENDS UPON DIETARY IRON CONCENTRATION FED TO C3H MICE . Journal of Nutritional Biochemistry. 18 (2007) 272-278. Interpretive Summary: From the results of the present study, we concluded that long term supplementation of AA in the setting of dietary iron loading inhibits lipid peroxidation and oxidative modification of DNA. In the absence of excess iron, AA was associated with a small increase in lipid peroxidation and decreased activity of SOD suggesting that AA can have mild prooxidant properties under certain conditions in vivo. The present observations together with our previous findings demonstrate that AA, has potent antioxidant properties against oxidative damage induced by dietary iron loading. However the exact mechanisms of this protection and whether they are operative in other forms of iron overload remain to be elucidated.
Technical Abstract: Ascorbic acid (AA) is an antioxidant that in the presence of iron and hydrogen peroxide increases the production of hydroxyl radicals in vitro. Whether AA has similar pro-oxidant properties in vivo may depend upon the relative balance of iron and ascorbic acid concentrations. In this study, C3H mice were fed diets supplemented with 100 mg iron/kg or 300 mg iron/kg with or without AA (15 g/kg) for 12 months. Liver AA concentrations were greater in mice fed AA supplemented diets with either low or high iron (P = 0.0001), while the high iron diet was associated with a significantly lower liver AA concentratin regardless of AA supplementation (P = 0.0001). Only mice fed the high iron diet with AA had a significantly greater liver iron concentration (P = 0.05). In the high iron group, AA reduced oxidative stress as measured by greater activities ofglutathione peroxidase, superoxide dismutase and catalase and significantly lower concentrations of 4-hydroxylalkenals (HAE) and malondialdehyde (MDA). In mice fed the low iron diet, AA was associated with greater concentrations of HAE and MDA and lower activities of superoxide dismutase. However, AA did not increase concentrations of modified DNA bases with the iron diet but was associated with significantly lower concentrations of modified DNA bases in mice fed the high iron diet. In conclusion, dietary AA appears to have mild pro-oxidant properties at low iron concentrations but has a strong anti-oxidant effect against oxidative stress and DNA damage induced by dietary iron in mouse liver.