Vitamin C suppresses oxidative lipid damage in vivo, even in the presence of iron overload

Ascorbate is a strong antioxidant; however, it can also act as a prooxidant in vitro by reducing transition metals. To investigate the in vivo relevan ce of this prooxidant activity, we performed a study using guinea pigs fed high or low ascorbate doses with or without prior loading with iron dextran . Iron-loaded animals gained less weight and exhibited increased plasma bet a -N-acetyl-D-glucosaminidase activity, a marker of tissue lysosomal membra ne damage, compared with control animals. The iron-loaded animals fed the l ow ascorbate dose had decreased plasma alpha -tocopherol levels and increas ed plasma levels of triglycerides and F-2-isoprostanes, specific and sensit ive markers of in vivo lipid peroxidation. In contrast, the two groups of a nimals fed the high ascorbate dose had significantly lower hepatic F-2-isop rostane levels than the groups fed the low ascorbate dose, irrespective of iron load. These data indicate that 1) ascorbate acts as an antioxidant tow ard lipids in vivo, even in the presence of iron overload; 2) iron loading per se does not cause oxidative lipid damage but is associated with growth retardation and tissue damage, both of which are not affected by vitamin C; and 3) the combination of iron loading with a low ascorbate status causes additional pathophysiological changes, in particular, increased plasma trig lycerides.