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Free radicals – what are they?
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Background
The generation of first organic free radical [Triarylmethyl radical] was reported by Moses Gomberg. Research has revealed that free radicals are present in the atmosphere, in our bodies and in some very important chemical reactions. The radical was formed by reacting triarylmethyl chloride with silver metal in benzene (Tidwell, 2001).
Free Radicals
Free radicals are organic molecules responsible for ageing, tissue damage and possibly some diseases. Free radicals are chemical species with one or more unpaired electrons in an outer orbital. Most of the free radicals are unstable, short lived and highly reactive. It is represented by a superscript dot next to the chemical structure (Karlsson, 1997).
In order to appreciate the role of free radicals in biology it is firstly necessary to understand their chemical structure. When a conventional molecular bond is broken, the two composite electrons usually split heterolytically or it is also possible for bonds to break homolytically. In non-biological systems, free radicals can be produced via the effects of ionising radiation, temperature and various photochemical events (Sun, 1990). Free radicals contain an odd number of electrons, which makes them unstable, short lived and highly reactive. As they combine with other atoms that contain unpaired electrons, new radicals are created, and a chain reaction begins. Once the process is started, it can continue, finally resulting in the disruption of a living cell (Goldfarb, 1999). There are many types of free radicals that can be formed within the body. The most important free radicals in biological systems are derived from oxygen, known as Reactive oxygen species or ROS, which includes the superoxide anion, the hydroxyl radical, singlet oxygen and hydrogen peroxide radicals. Reactive oxygen species have been implicated in the pathogenesis of several human diseases (Vallyathan et al., 1998). Hydroxyl radical is highly reactive and one of the most oxidising species in living systems. Hydroxyl radicals have the ability to react with cellular bio molecules, including DNA, lipids and protein (Breen and Murphy, 1995). This cellular damage can result in a number of modifications, the consequences of which may include cell death, apoptosis and mutagenesis. The pathogenesis of several human diseases such as brain ischemia, Parkinson’s disease, rheumatoid arthritis, respiratory distress syndrome, cardiovascular disease and carcinogenesis have been directly linked to hydroxyl radicals (Halliwell, 2001). Free radicals are produced in cells by electron transfer reactions, which can be enzymatically mediated or non-enzymatically mediated. The production of free radicals in cells can happen both accidentally and deliberately. An example of deliberate reactions is the superoxide generated by active phagocytes and in catalytic reactions e.g. Ribonucleotide reductase. An example of accidental generation free radicals are produced only at the interface of phagocyte plasma membrane and bacterium, some leakage of superoxide, hydrogen peroxide and reactive oxygen species is inevitable. Under normal circumstances, the major source of free radicals in cells is the electron leakage that happens from electron transport chains, such as those in the mitochondria and endoplasmic reticulum, to molecular oxygen generating superoxide (Latha and Babu, 2001). The studies that have looked into the involvement of these species in such diseases have generated a significant amount of interest in this area. There is a great deal of interest in the detection and generation of free radicals and their by-products in vitro and in clinical situations.
Measurement of Free Radicals
Measurement of free radicals is very difficult and the increasing interest in the role of Hydroxyl radicals in the pathogenesis of disease has lead to an increased need for techniques to measure the effect of its damage upon cells both in vitro and in vivo. Electron spin resonance spectrometry is the only analytical technique that directly measures the free radicals. However, it is relatively insensitive to detect directly. In order to detect unstable free radicals spin trapping technique was introduced. Spin trapping involves the addition of a compound known as spin trap, that react rapidly with free radicals to form radical adducts that are very much more stable and longer lived than original species (Pou et al., 1989).
Benefits of Free Radicals
The many chemical reactions that occur in the body inevitably produce free radicals. The body can, however, usually keep these free radicals under control. Moreover, despite the long list of problems they cause, free radicals are not at all bad. They play an essential role in a healthy human body. The immune system is the main body system that utilises free radicals. Foreign invaders or damaged tissue is marked with free radicals by the immune system. This allows for the determination of which tissues need to be removed from the body. Because of this some question the need for antioxidant supplementation, as they believe supplementation can actually decrease the effectiveness of the immune system. Free radicals play an important function in biological process, such as intracellular killing of bacteria by neutrophil granulocytes. Free radicals have also implicated in cell signalling processes. The two most important radicals which are derived from molecular oxygen are superoxide [O2.-] and hydroxyl radical [OH.]. However, because of their reactivity, these same free radicals can participate in unwanted side reactions resulting in cell damage. Many forms of cancer are thought to be the result of reactions between free radicals and DNA, resulting in mutations that can adversely affect cell cycle and potentially lead to malignancy (Breen and Murphy, 1995). Some of the symptoms of ageing such as atherosclerosis are also attributed to free radical induced oxidation of many of the chemicals making up the body. In addition free radicals contribute to alcohol-induced liver damage, perhaps more than alcohol itself (Cederbaum, 1989)
REFERENCES
BREEN, A. P. & MURPHY, J. A. 1995. Reactions of oxyl radicals with DNA. Free Radic Biol Med, 18, 1033-77.
CEDERBAUM, A. I. 1989. Oxygen radical generation by microsomes: role of iron and implications for alcohol metabolism and toxicity. Free Radic Biol Med, 7, 559-67.
GOLDFARB, A. H. 1999. Nutritional antioxidants as therapeutic and preventive modalities in exercise-induced muscle damage. Can J Appl Physiol, 24, 249-66.
HALLIWELL, B. 2001. Role of Free Radicals in the Neurodegenerative Diseases: Therapeutic Implications for Antioxidant Treatment. Drugs & Aging, 18, 685-716.
KARLSSON, J. 1997. Introduction to Nutralogy and Radical formation. In: Antioxidants and Excercise. Ilinois: Human Kinetic Press
LATHA, B. & BABU, M. 2001. The involvement of free radicals in burn injury: a review. Burns, 27, 309-317.
POU, S., HASSETT, D. J., BRITIGAN, B. E., COHEN, M. S. & ROSEN, G. M. 1989. Problems associated with spin trapping oxygen-centered free radicals in biological systems. Anal Biochem, 177, 1-6.
SUN, Y. 1990. Free radicals, antioxidant enzymes, and carcinogenesis. Free Radical Biology and Medicine, 8, 583-599.
TIDWELL, T. T. 2001. The Gomberg century: Free radicals 1900-2000. Advances in Physical Organic Chemistry. Academic Press.
VALLYATHAN, V., SHI, X. & CASTRANOVA, V. 1998. Reactive Oxygen Species: Their Relation to Pneumoconiosis and Carcinogenesis. Environmental Health Perspectives, 106, 1151-1155.
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