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 relevance 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 beta-N-acetyl-D-glucosaminidase activity, a marker of tissue lysosomal membrane damage, compared with control animals. The iron-loaded animals fed the low ascorbate dose had decreased plasma alpha-tocopherol levels and increased plasma levels of triglycerides and F(2)-isoprostanes, specific and sensitive markers of in vivo lipid peroxidation. In contrast, the two groups of animals fed the high ascorbate dose had significantly lower hepatic F(2)-isoprostane levels than the groups fed the low ascorbate dose, irrespective of iron load. These data indicate that 1) ascorbate acts as an antioxidant toward 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 triglycerides.
Chen
K
K
The Evans Memorial Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston 02118, USA.
Suh
J
J
Carr
A C
AC
Morrow
J D
JD
Zeind
J
J
Frei
B
B
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D028441:F2-Isoprostanes; D005260:Female; D006168:Guinea Pigs; D019190:Iron Overload / Q000139:chemically induced / Q000378:metabolism*; D007505:Iron-Dextran Complex; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
D000975:Antioxidants; D028441:F2-Isoprostanes; D007505:Iron-Dextran Complex; D015237:Dinoprost; D001205:Ascorbic Acid