Chapter 3Biomarkers
Section snippets
Introduction – Why do we need `biomarkers?
The term `biomarker' has been adapted from molecular epidemiology by free radical biologists to describe a molecular change in a biological molecule that has arisen from attack by reactive oxygen, nitrogen or halide species (Offord et al., 2000). It is applied equally to products derived from lipids, DNA, proteins and antioxidant consumption, where the chemical nature of the reaction may be proton abstraction, electron transfer or direct addition. Rates of reaction of these molecules with the
Introduction: biochemistry of lipid peroxidation
The principal lipid-rich sites in vivo are the lipid-carrying lipoproteins and cell membranes. Increased concentrations of lipid peroxidation end products are found in most, if not all, human diseases. However, they play a significant pathological role in only some of them. For example, peroxidation appears to be important in atherosclerosis, and in worsening the initial tissue injury caused by ischemic or traumatic brain damage. Lipid peroxidation often occurs late in the injury process. Many
Biochemistry: histochemical detection of ROS
Several of the biochemical changes induced by oxidant stress can be directly detected in tissue and cells by histochemical means. The determination of such `histochemical biomarkers' has been used to discriminate areas, cellular types and, sometimes, subcellular sites affected by oxidant stress, in experimental models as well as in control tissue.
Method of measurement
The reduction of nitroblue tetrazolium to insoluble blue formazan has been widely used, especially in studies using activated phagocytes, to evaluate
Background
The critical review of the role of oxidative stress in the regulation of gene expression in Chapter 4 raises the issue that the effects of ROS/RNS are not always deleterious, but play an important role in normal cellular signalling processes. This function appears likely to be both dose- and microenvironment-dependent. However, in circumstances of elevated oxidative stress, oxidants can elicit de novo synthesis and post-transcriptional activation of enzymes involved in detoxification, where
Conclusions
Herein, we have identified strengths and weaknesses in the different methodologies available for biomarker measurement, and reviewed the use of these techniques in supplementation studies. Specifically, a set of criteria has been established that allow us to identify the validity of each methodology, and more importantly, identify areas for further study. These are defined in priority order as: (i) specificity (both biological in terms of source, and chemical in terms of analysis), (ii)
Future research needs
Key requirements arising from this work are:
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the establishment of an ESCODD-style validation study for all the favoured biomarkers described in Table 19;
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a re-examination of the kinetics of oxidative biomarker formation and their respective half-lives. This can then be superimposed on knowledge of the kinetics of antioxidant availability at the target site, as raised by Bioavailability and metabolism. Many of the discrepancies in studies to date may be explained by viewing biomarker changes in
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