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 susceptibilit y to lipid peroxidation in an age-dependent manner. Young (6 month) and old (24 month) male B6C3F1 mice were fed modified AIN-76 diets containing eith er 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 Jive 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 w ith 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 ho urs post-injection. Microsomal membrane fatty acid analysis revealed that i ncreased age and a FO diet significantly increased membrane PUFA content. S erum 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 followi ng 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 a ccumulation, and the liver microsomal membranes of old mice were more unsat urated, yet there was significantly greater peroxidative damage (MDA format ion) and cell death (apoptosis) in the young mouse livers. These findings s uggest that the older animals have upregulated antioxidant defenses. (C) 19 98, Editrice Kurtis.