Age-independent, gray matter-localized, brain-enhanced oxidative stress in male fischer 344 rats: brain levels of F2-isoprostanes and F4-neuroprostanes

While studies showed that aging is accompanied by increased exposure of the brain to oxidative stress, others have not detected any age-correlated differences in levels of markers of oxidative stress. Use of conventional markers of oxidative damage in vivo, which may be formed ex vivo and/or eliminated by endogenous metabolism, may explain these conflicting results. Recently, F2-isoprostanes and F4-neuroprostanes, peroxidation products of arachidonic acid and docosahexaenoic acid, respectively, have been identified as sensitive and reliable markers of oxidative injury. Therefore, this study was designed to quantify brain levels of F2-isoprostanes and F4-neuroprostanes and their precursors in 4, 10, 50, and 100 week old male Fischer 344 rats. Data show that levels of F2-isoprostanes and F4-neuroprostanes were comparable in all animal age groups. However, levels of F4-neuroprostanes were approximately 20-fold higher than those of F2-isoprostanes in all age groups, despite the fact that brain levels of docosahexaenoic acid were only twice as high as those of arachidonic acid. Based on our findings, it is concluded that aging is not accompanied by enhanced brain susceptibility to oxidative stress. Furthermore, the metabolically active gray matter of the brain, where docosahexaenoic acid is abundant, appears more susceptible to oxidative stress than the white matter.