Sources of Oxidative Stress

The inabihty of the neurons to eliminate the oxidative load may result in a self-perpetuating cycle of oxidative damage that ultimately leads to neuronal death. One source of oxidative stress may be dopamine metabolism (Fig. 31.2). The excessive excitatory activity in the substantia nigra created by the loss of dopamine actions within the striatum could lead to excitotoxicity that is mediated by glutamate. 

Cigarette smoking is a major risk factor for coronary disease. It is associated with reduced levels of HDL, impairment of cholesterol retrieval, cytotoxic effects on the endothelium, increased oxidation of lipoproteins, and stimulation of thrombogenesis. Diabetes, also a major risk factor, is another source of oxidative stress. 

Therefore, this incomplete reduction may lead to redox cycling, and the presence of nitrated proteins in the cell may be a source of oxidative stress (K25). 

F19. Fu, S., Fu, M. X., Baynes, J. W., Thorpe, S. R., and Dean, R. T., Presence of dopa and amino acid hydroperoxides in proteins modified with advanced glycation end products (AGEs) Amino acid oxidation products as a possible source of oxidative stress induced by AGE proteins. Biochem. J. 330, 233-239 (1998). 

Reactive oxygen species (ROS), oxidative stress and the environment form a complex relationship with important influence on human health and disease. Environmental oxidative stress derives from different artificial and natural sources (Fig. 1) and is induced by several different mechanisms. To address the complexity of this field, this chapter will deal with the modes of action by which environmental factors can disturb the equilibrium between pro- and antioxidants favouring the former (for definition of oxidative stress see [1]). Adjacent, environmental sources of oxidative stress and their mode of action will be introduced. 

R.P. Mason, Free radical metabolites of toxic chemicals and drugs as sources of oxidative stress, in Biological Consequences of Oxidative Stress. Implications for Cardiovascular Disease and Carcinogenesis, L. Spatz and A.D. Bloom (eds.), Oxford University Press, New York, 1992, p. 23. 

Wang, Y., and Walsh, S.W., 1998, Placental mitochondria as a source of oxidative stress in pre-eclampsia. Placenta. 19 581-586. 

As for iron, differences in redox potentials are relatively small between the major oxidation states of copper, that is, Cu(I) and Cu(II). This gives copper its main function as a cofactor in enzymatic reactions involving electron-transfer processes. In the human body, most of the copper (about 40%) is present in muscle tissue with significant amounts also present in the liver, brain, and skeleton. About 5% of the copper can be found in serum, of which 80-90% is present as ceruloplasmin. Ceruloplasmin in serum and hephaestin at the basolateral side of the mucosa ensure oxidation of circulating Fe to Fe for iron binding to transferrin. Unbound Fe is a major source of oxidative stress through Fenton/Haber-Weiss chemistry. Copper together with zinc is also a cofactor for superoxide dismutase, a key molecule in the anti-oxidant defense system of the body ]74]. 

To identify if the inability of tocopherol to protect mitochondrial proteins is specific to the source of oxidative stress, xanthine oxidase, was also applied to the plant membranes. While proteolysis was not as severe for the mitochondrial membranes as it had been when iron-ascorbate was the initiating agent, the proteolysis in mitochondrial membranes still exceeded the proteolysis in either of the microsomal membrane fractions (Figure 5a). In addition, tocopherol loss does not precede proteolysis for the mitochondrial fraction and this was also the case for the microsomal fractions (Figure 5b). Based on these data and the preceding data for iron-ascorbate, it would appear that tocopherol is limited in its ability to... 

Nutrition is a factor gaining more and more importance in terms of oxidative stress. Besides the known protective effects of healthy nutrition (see below), it can also be responsible for arising oxidative stress. Nutrition is not strictly an environmental noxa itself but it represents a blend of several noxae (e.g. radioactive isotopes, particulate matter, nitric oxides). Pre-noxae, primarily less or not dangerous, can be modified by the organism (e.g. via cytochrome P450 systems) and represent a major factor in oxidative stress induced by nutrition. Such modification, as in the xenobiotic metabolism, might lead to potential sources for oxidative stress. 

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