Age-dependent sensitization to oxidative stress by dietary fatty acids

Experiments were designed to test the hypothesis that short-term feeding of a high polyunsaturated fatty acid (PUFA) diet would increase susceptibility to lipid peroxidation in an agedependent manner. Young (6 month) and old (24 month) male B6C3F1 mice were fed modified AIN-76 diets containing either 5% corn oil (CO, N=5 per age group) or 19% fish oil plus 1% corn oil (FO, N=20 per age group) for two weeks. Five CO and five FO diet mice per age received an intraperitoneal injection of normal saline and were sacrificed one hour later; the remaining FO diet mice (N=15 per age) were challenged with an acute systemic oxidative stress by intraperitoneal injection of 125 mg iron/kg body weight as iron dextran, and were sacrificed 1, 5, and 24 hours post-injection. Microsomal membrane fatty acid analysis revealed that increased age and a FO diet significantly increased membrane PUFA content. Serum iron levels increased significantly following iron treatment, peaking at 5 hours in both age groups. Formation of microsomal malondialdehyde (MDA), a product of lipid peroxidation, was significantly greater in the livers of the young mice. The temporal patterns of serum iron and microsomal MDA concentrations were significantly correlated in young mice, but not in old mice. Histochemical examination showed that liver iron accumulation following iron injection was similar in both age groups, but was associated with a significant temporal increase in liver apoptotic cells in young mice, but not in old mice. Thus, both age groups had similar iron exposure and iron accumulation, and the liver microsomal membranes of old mice were more unsaturated, yet there was significantly greater peroxidative damage (MDA formation) and cell death (apoptosis) in the young mouse livers. These findings suggest that the older animals have upregulated antioxidant defenses.