Reactive oxygen species: relation to aging and neurotoxic damage.
The inherent biochemical, anatomical and physiological characteristics of the brain make it especially vulnerable to oxidative insult. Some of the features which account for a susceptibility to free radical induced insult, include a high lipid content, a major requirement for oxidative energy metabolism, and a paucity of enzymes dissipating reactive oxygen species. Recently it has become increasingly apparent that many drug and chemical-induced toxicities may be evoked by way of oxidative stress. Major points addressed in this presentation relate to xenobiotic-induced disruption of cerebral redox status, specific examples of neurotoxic agent-induced alterations in free radical production, as measured by the fluorescent probe dichlorofluorescein, and the regulation of neural free-radical generation by antioxidants and protective enzymes. Recent attempts to unify the diffuse discipline of neurotoxicology, have led to the concept of "final common pathways" that characterize frequently occurring cellular responses to disruption of homeostasis resulting from exposure to xenobiotic agents. The present work considers the thesis that oxygen radicals may be mediators of such a "final common pathway". Free radical mechanisms may thus contribute significantly to the expression of the harmful properties of diverse, unrelated neurotoxic agents. Studies with aged animals suggest that, while excess levels of oxidative species are not apparent in the aged central nervous system, prolonged exposure to such species may adversely modify proteins, and this may be a contributing factor to senescence. The extent to which normal physiologic aging and neurotoxic events interact, remains to be determined.
Bondy
S C
SC
Department of Community and Environmental Medicine, University of California, Irvine 92717.
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D005609:Free Radicals; D009420:Nervous System / Q000187:drug effects*; D010100:Oxygen / Q000502:physiology*
D005609:Free Radicals; D010100:Oxygen