BACKGROUND: Free radical-mediated oxidative damage has been implicated in a variety of pathological processes such as diabetes mellitus, aging and atherosclerosis. The susceptibility of a given organism to oxidative damage is influenced by the overall balance between the degree of oxidative stress and antioxidative capabilities. Nutrition plays an important role in determining the cellular antioxidative defense mechanism. Thus, the aim of this study is to investigate the effects of fetal protein malnutrition on oxidative stress and antioxidative capabilities. METHOD: Rats were fed a low-protein (8% casein) diet throughout pregnancy and lactation. Male offspring were weaned onto either a control (18% casein) diet (group 2) or a low-protein diet (group 3). Offspring from rats fed a control diet were weaned onto a control diet (group 1). The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and the concentration of thiobarbituric acid- reactive substances (TBARS) were determined at 10 and 15 wk in liver and skeletal muscle from offspring. RESULTS: SOD activities of liver in group 3 were significantly lower than those in group 1 at 10 wk (4.14+/-0.65 U/mg protein, 9.09+/-0.85 U/mg protein) and 15 wk (4.18+/-0.58 U/mg protein, 7.63+/-0.74 U/mg protein), respectively. But SOD activities of skeletal muscle were not different between groups. Whilst GPx activities of liver were not different at 10 wk, GPx activities in group 2 (1.80+/-0.16 U/mg protein) were significant higher than those in group 1 (1.24+/-0.15 U/mg protein) at 15 wk. GPx activities of skeletal muscle were not different between groups. The TBARS concentrations in liver or skeletal muscle were not different between groups at 10 and 15 wk. There was a significant negative correlation between SOD activities and TBARS concentrations in liver (r=-0.359). CONCLUSION: In offspring of rats fed a low-protein diet throughout pregnancy and lactation, the antioxidant enzyme activities were significantly decreased, compared with offspring of rats fed a control diet. These alterations were not fully restored in low-protein offspring even when weaned onto a control diet. These results suggest that fetal protein malnutrition impair the antioxidative defense system.