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Mechanisms and Biomarkers (WG 4) page 33
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protection against lipid peroxidation in vitro suggests but does not prove the capacity to
protect in vivo. As a measurement of lipid peroxidation in humans the much used TBARS
assay is now largely discredited due to the confounding influence of diet, (Brown et al., 1995)
and formation of arachidonic acid metabolic products can be misinterpreted (Stocker, 1999) .
Also lipid peroxides and their decomposition products including MDA can be absorbed from
the diet and aldehydes re-excreted in the urine (Grooveld et al., 1998; Aw, 1998). A more
reliable biological biomarker for LDL oxidation in vivo may be an assay of circulating antibodies
against oxidised LDL (Yla-Herttualla, 1998).
Isoprostanes - The F2 isoprostanes are specific peroxidation products arising from arachidonic
acid residues in lipids (Pratico et al., 1997) and offer promise as specific biomarkers of lipid
peroxidation in the human body. Mean levels are raised in conditions associated with
oxidative stress (Mallat et al., 1998) and steady state levels in human plasma can be readily
detected by sensitive mass spectrometric techniques. Urinary detection of isoprostanes may be
a useful non invasive biomarker for whole body lipid peroxidation (Basu, 1998). However,
the primary source from which the unmetabolised F2 isoprostanes in urine originate is not
known. They may originate from plasma via filtration in the kidney from formation in the
kidney or from a combination of both. Further, a lack of validated assays for isoprostanes
other than those based on mass spectrometry has still reduced its general applicability as a
potential biomarker. However, several immunological assays have been developed to detect
non cyclo-oxygenase derived isoprostane F2 (Wang et al., 1995).
Breath Alkanes - As common end-products of lipid peroxidation the alkanes present
superficially attractive candidates as non-invasive biomarkers for the process and its
involvement in disease states.
Ethane and pentane have been commonly used to assess lipid peroxidation in both in vivo and
in vitro studies following the pioneering studies of Riely et al. (1974). Improvements in
analytical procedures enabled the measurement of other volatile alkanes such as ethane,
propane, n-butane, iso-pentane and iso-butane (Frank et al., 1980). Feeding studies with rats
yielded a relationship between the mono and poly unsaturated fatty acids (PUFA) ingested
and the alkanes identified in the breath samples. Oxidation of ω-3 PUFA increased ethane
excretion, while ω-4 PUFA, ω-6 PUFA, and ω-7 PUFA oxidation yielded increased excretion
of propane, pentane, and hexane respectively (Kivits et al., 1981). The PUFA content of liver
depends closely on the nature and quantity of PUFA in the diet, and in turn the exhaled
alkanes in rats subject to oxidative stress corresponded well with the composition of the liver
phospholipids in terms of the fatty acid profile. ω-3 and ω-6 PUFAs are the most abundant