Oxygen free radicals and the disease process
Whitaker, Sally H
Free radicals play a key role in both normal biological function and in the pathogenesis of many disease processes. These free radicals are continuously formed in the body and are exquisitely balanced.1-4 When this balance is broken, oxidative stress occurs. During oxidative stress, cellular lipids, DNA, and proteins are attacked causing damage to the cells and resulting in a loss of function, integrity, and ultimately, cellular death.4-6
Most molecules can become free radicals by either losing or gaining an electron. During this chemical process, molecules can be either reduced or oxidized. A single electron in an orbital is said to be “unpaired”. Thus, a radical is defined as any species that contains one or more unpaired electrons capable of independent existence.7 When electrons are paired, the molecule is chemically stable in contrast to a molecule with an unpaired electron.5,6 An orbital that has only one electron will try to fill it by “stealing” another unpaired electron from the orbital of another molecule. The donation of an electron is called oxidation and the gain of an electron is called reduction.8
Most chemical reactions in the body are “balanced” through reduction and oxidation mechanisms (redox). Redox reactions primarily involve the transfer of electrons between two chemical species.
The compound that loses an electron is said to be oxidized; the one that gains an electron is said to be reduced.1,2
It is important to remember that the human body attempts to maintain a balance between the reactive oxygen species production and the levels of antioxidants. This balance is often referred to as the ‘redox potential’, and any interference of the balance may lead to cellular damage.1,4
Changing the balance toward an increase in oxidants is called Oxidative stress’, and changing the balance toward an increase in the reducing power, or antioxidants, is called ‘reductive stress’.1,2,4,6,12 When a patient has normal production of free radicals and antioxidants needed for health, the scale is balanced.
However, overproduction of free radicals or antioxidants can shift the balance to produce oxidative stress. Maintaining redox balance has two major advantages: the ability to remove or neutralize toxic levels of oxidants before cellular damage occurs, and the ability to manipulate changes at the subtoxic level by initiating redox signaling.1,6 Antioxidants, therefore, control the relationship between reducing or oxidizing (redox) in the body.
Antioxidants interrupt the chain-reaction, by either removing free oxygen radicals, preventing their formation, or by repairing the damage they cause within the cell structure.” Few well-designed studies have been conducted that clearly outline the recommended amounts of multivitamin and mineral supplements. One textbook, Herbal Therapies and Supplements: A Scientific and Traditional Approach is a good resource for clinicians.9
D-alpha-tocopherol, is the most active natural form of vitamin E. Recent evidence indicates that an intake of about 100-200 IU of vitamin E per day may lower the risk of heart disease.7 A recommended supplemental dose is 400-800 IU/day. For hot flashes, a recommended dose is 400 IU in the A.M. and 800 IU at bedtime. For vaginal dryness, some clinicians have recommended opening a vitamin E capsule and spreading the oil on the vagina daily for 5-6 weeks and then weekly thereafter.9
Vitamin C is a water-soluble antioxidant. Studies have shown vitamin C forms the first line of antioxidant defense in plasma against many types of free radicals, and may be more effective against LDL oxidation than vitamin E.11 There is strong evidence that an adequate intake of vitamin C may lower the risk of cancer, heart disease and cataract formation.12,13 A low dose is recommended (200 mg) except when a patient experiences cold symptoms, in which case the dose may be increased to 600-800 mg.9 Higher doses are excreted in the urine and not utilized by the body.
The role of oxygen-free radicals in the pathogenesis of disease processes is well accepted. Np’s need to intervene and instruct patients on the impact that this process might have on overall health.
Practitioners need to be able to discuss the various actions, uses, and potential for abuse of antioxidants with their patients to help them make knowledgeable decisions about antioxidant supplements.
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3. Wilson JN, Pierce JD, Clancy RL: Reactive oxygen species in acute respiratory distress syndrome. Heart Lung 2001;30:370-5.
4. Kohen R, Nyska A: Oxidation of biological systems: Oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Path 2002;30(6):620-650.
5. Dalton TP, Shertzer HG, Puga A: Regulation of gene expression by reactive oxygen. Annu Rev Pharmacol Toxicol 1999;39:67-101.
6. Gutteridge JMC, Mitchell, J: Redox imbalance in the critically ill. Br Med Bull 1999;55(1): 49-75.
7. Gieseg SP: Reducing free radicals – A dietary revolution. New Zealand Science Monthly 1999;8:6-8.
8. Goodyear-Bruch C, Pierce JD: Oxidative stress in critically ill patients. Am J Crit Care 2002;11:543-551.
9. Kuhn M, Winston D: Herbal therapies and supplements: A scientific and traditional approach. Philadelphia, PA, Lippincott, 2001.
10. Tribble DL: AHA Science Advisory. Antioxidant consumption and risk of coronary heart disease: Emphasis on vitamin C, vitamin E, and betacarotene: A statement for healthcare professionals from the American Heart Association. Circulation 1999;99:591-595.
11. Schoonover LL: Oxidative stress and the role of antioxidants in cardiovascular risk reduction. Prog Cardiovasc Nurs 2001;16(1): 30-32.
12. McDermott JH: Antioxidant nutrients: Current dietary recommendations and research update. J Am Pharm Assoc 2000;40(6): 785-799.
13. Yusef S, Dagenais G, Pogue J, et al.: Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:154-160.
This article was supported by grant RO1NR0531701A1 from the National Institute of Nursing Research, National Institutes of Health.
Sally H. Whitaker, RN
Janet D. Pierce, DSN, ARNP
ABOUT THE AUTHORS
At the University of Kansas School of Nursing, Kansas City, Janet Pierce is an Associate Professor and Sally H. Whitaker is a graduate student.
Copyright Springhouse Corporation Aug 2003
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