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Mechanisms and Biomarkers (WG 4) page 32
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the current methodologies for analysing oxidative protein damage in vivo have not reached a
sufficient degree of sophistication for universal use (Dean et al., 1998).
In this report we wish to make the distinction between biomarkers of cellular insult/protection
measured as simple chemical end points (8-oxoG, o-OH Tyr, MDA, HNE etc.) and the more
complex biochemical, genetic and histological changes associated with oxidative stress and
injury. Chemical biomarkers will be affected to a greater extent than biological end points by
the often complex multi-step work up procedures. Biological end points usually involve direct
measurement of relevant parameters (gene expression, chromosome damage, tumour
regression and ultra-sound plaque measurement etc.) and are perhaps less subject to artifactual
variation, and may be more relevant indicators of disease progression. An ideal biomarker
should possess the following properties:
1. Highly specific for the process under scrutiny.
2. Identifiable at an early stage in the investigation.
3. Simple and reproducible method(s) of analysis.
4. Obtainable by non or minimally invasive procedures (urine, blood).
5. Low background contamination.
6. Unequivocal response of biomarker to exposure.
7. Proven relationship between the biomarker and modulation in damage/protection.
Chemical Biomarkers
Biomarkers of Lipid Peroxidation.
Development of accurate methods for measuring in vivo lipid peroxidation has been even
more difficult than developing optimum methods for detection of oxidative DNA damage.
The major reason for this is that LDL peroxidation that contributes to atherosclerosis occurs
within the vessel wall not in the peripheral circulation (Steinberg and Lewis, 1997). However,
since minimally oxidised LDL can escape recognition by the macrophages, and re-enter the
circulation, the measurement of ex-vivo LDL peroxidation may be a potentially useful
biomarker. It should also be noted that ex-vivo LDL peroxidation studies will not reflect the
potential protective role of other antioxidant substances such as vitamin C that may be lost
during the LDL isolation procedure. Lipid peroxidation is commonly initiated using Cu 2+ ion.
Although there is evidence to suggest that copper plays a role in lipid peroxidation (Ferns et
al., 1997) there is also data indicating that RS can also be involved (Luoma et al., 1998), and
the oxidative mechanism may differ between lesions. The demonstration of antioxidant