Regulation of physiological systems by nutrientsFree radicals, antioxidants, and nutrition
Introduction
Radiation hazards in outer space, such as the Earth’s radiation belt (primarily protons and electrons captured by the geomagnetic field), solar space radiation (primarily protons and α-particles), and galactic space radiation (primarily protons, α-particles, and heavier nuclei), present an enormous challenge for the biological safety of manned space missions.1 A deleterious effect of radiation is the production of reactive oxygen species (ROS), which include superoxide anion (O2−, a free radical), hydroxyl radical (•OH), and hydrogen peroxide (H2O2).2 These reactive species may contribute to radiation-induced cytotoxicity (e.g., chromosome aberrations, protein oxidation, and muscle injury) and to metabolic and morphologic changes (e.g., increased muscle proteolysis and changes in the central nervous system) in animals and humans during space flight.3, 4, 5 Although space radiation hazard can be reduced primarily by radiation shielding,1 dietary antioxidants may be useful radioprotectors to protect astronauts against radiation-induced tissue lethality and other deleterious effects.6, 7, 8
For designing an optimal nutritional countermeasure against space radiation, it is necessary to fully understand the mechanisms responsible for the production and removal of free radicals and other reactive species. Since the discoveries of the catalytic function of superoxide dismutase (SOD) in 19699 and the arginine-dependent synthesis of nitric oxide (•NO), a nitrogen free radical, in 1988,10 there has been rapid progress in the field of free radical biology.11, 12, 13 Over the past three decades, the free radical theory has greatly stimulated interest in the role of dietary antioxidants in preventing many human diseases including cancer, atherosclerosis, stroke, rheumatoid arthritis, neurodegeneration, and diabetes.12, 13, 14, 15, 16 The knowledge of enzymatic and non-enzymatic oxidative defense mechanisms will serve as a guiding principle for establishing the most effective nutrition support to ensure the biological safety of manned space missions. With this proposition, the major objective of this article is to review recent advances in free radical biology and antioxidant nutrients, with emphasis on oxidative defense systems against radiation-induced radical damage.
Section snippets
What are free radicals?
Free radicals are defined as molecules having an unpaired electron in the outer orbit.12 They are generally unstable and very reactive. Examples of oxygen free radicals are superoxide, hydroxyl, peroxyl (RO2•), alkoxyl (RO•), and hydroperoxyl (HO2•) radicals. Nitric oxide and nitrogen dioxide (•NO2) are two nitrogen free radicals. Oxygen and nitrogen free radicals can be converted to other non-radical reactive species, such as hydrogen peroxide, hypochlorous acid (HOCl), hypobromous acid
Protein
The net loss of body protein, in particular skeletal muscle protein, is likely a major factor responsible for protein malnutrition7, 8 and possibly deficiencies of some amino acids (e.g., glutamine, arginine, and cysteine) during space flight. Interestingly, radiation directly contributes to the increased muscle proteolysis and muscle atrophy under space flight conditions.3 Amino acids are building blocks for the synthesis of proteins, including antioxidant enzymes. Some amino acids (e.g.,
Perspectives and future directions
With the development of long-term manned space missions and permanent space habitats, the protection of astronauts from radiation injury has emerged as a crucial issue of biological safety in space travel.4, 8, 86 The adverse effects of long-term exposure to the space environment such as the very intense random solar energetic particles and the low-density heavy-ion flux of the galactic cosmic rays, which increase the risk of tissue injury, DNA damage, and cancer induction,3, 5 are a major
Acknowledgements
The authors thank Tony Haynes for assistance in manuscript preparation and Frances Mutscher for office support. The excellent comments of Drs. Xin-Gen Lei, Joanne R. Lupton, Wilson G. Pond, and Nancy D. Turner on this manuscript are gratefully appreciated. Work in G. Wu’s laboratory is supported, in part, by grants from United States Department of Agriculture, American Heart Association, and Juvenile Diabetes Research Foundation. G. Wu is an Established Investigator of the American Heart
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