Reactive oxygen species

Free radicals are highly reactive molecules containing one or more unpaired electrons. Examples of free radicals are the superoxide anion (O-0 and the hydroxyl radical (OH-). The term 'reactive oxygen species' is a collective one that includes not only oxygen-centred radicals but also some non-radical derivatives of oxygen, such as hydrogen peroxide (H2O2), singlet oxygen and hypochlorous acid (HOCl). Hydrogen peroxide can very easily break down, particularly in the presence of transition-metal ions (e.g. ferrous (Fe2+) iron), to produce the hydroxyl radical, the most reactive and damaging of the oxygen free radicals:

H2O2 + Fe2+ ^ OH- + OH- + Fe3+

  • CAB International 2002. Nutrition and Immune Function
  • eds P.C. Calder, C.J. Field and H.S. Gill) 171

Exogenous sources of free radicals include ozone, UV radiation and cigarette smoke. Free radicals are also generated endogenously, mainly from two sources. The first is by leakage from the mitochondrial electron-transfer chain, as part of normal cellular metabolism. The second is as part of the respiratory-burst activity of leucocytes, which is involved in microbial killing.

ROS can cause damage to all of the major classes of macromolecules. They cause strand breaks in DNA (Halliwell and Aruoma, 1991), which can potentially lead to subsequent misrepair, mutation and tumour-cell formation. An example of free-radical-mediated damage to proteins is the formation of cataracts, resulting from the damage to the crystallins in the lens of the eye. However, lipids are probably most susceptible to free radical attack, particularly long chain polyunsaturated fatty acids (PUFA) that contain several double bonds. The oxidative destruction of PUFA, known as lipid peroxidation, can be extremely damaging, since it proceeds as a self-perpetuating chain reaction.

Generation of ROS in excess of the amounts that can be dealt with by the body's antioxidant protective mechanisms is thought to be a major contributor to several degenerative disorders, such as cancer and cardiovascular diseases (Table 9.1), and to the ageing process. Strong associations between diets rich in antioxidant nutrients and a reduced incidence of cancer have been observed in several epidemiological studies (Block et al., 1992; Giovannucci, 1999), and it has been suggested that a boost to the body's immune system by antioxidants might, at least in part, account for this (Bendich and Olson, 1989). Indeed, it is probably crucial to attempt to balance the production of ROS and the antioxi-dant defence system, ideally by dietary means rather than by taking supplements, from as early an age as possible, in order to delay the onset of, if not prevent, many age-related disorders.

The immune system appears to be particularly sensitive to oxidative stress. Immune cells rely heavily on cell-cell communication, particularly via membrane-bound receptors, to work effectively. Cell membranes are rich in PUFA, which, if peroxidized, can lead to a loss of membrane integrity, altered membrane fluidity (Baker and Meydani, 1994) and alterations in intracellular signalling and cell function. It has been shown that exposure to ROS can lead to a reduction in cell-membrane-receptor expression (Gruner et al., 1986). In addition, the production of ROS by phagocytic immune cells can damage the cells themselves if they are not sufficiently protected by antioxidants.

Table 9.1. Degenerative disorders associated with oxidative damage.

Cancer

Cardiovascular disease

Stroke

Cataract

Degeneration of the macula region of the retina

Immunosenescence

Ageing

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