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Mechanisms and Biomarkers (WG 4) page 46
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In a recent study (Lowe, 1999) adenocarcinoma HT29 cells were supplemented with either β-
carotene or lycopene. The cells were then challenged with superoxide and hydrogen peroxide
generated by xanthine/xanthine oxidase. Cellular damage was assessed using ethidium
bromide to monitor insult to the plasma membrane, whilst the comet assay was used to assess
DNA single strand breaks. Low concentrations (1µM) of carotenoid afforded protection to the
cells. This may reflect the efficiency of the carotenoid to scavenge radicals in the depth of the
membrane and prevent the onset of lipid peroxidation. When greater concentrations were
employed (> 4µM) the membrane would be expected to become more fluidic and allow
greater oxidant damage to occur. Following free radical challenge the cells were not necrotic
nor did they release significant amounts of LDH, but ethidium bromide uptake was increased
and this indicated that the cells had indeed become permeabilised particularly when higher
doses of carotenoids were used. This would allow the uptake of small molecules in a non-
regulated manner, therefore exacerbating further ROS damage to the cell.
Another protective mechanism by which either lycopene and β-carotene may reduce the
incidence of atherosclerosis is by the reduction of circulating plasma cholesterol. Work by
Fuhrman (1997) suggests this may be acheived by the carotenoids regulating HMGCoA
reductase expression. This inhibition is believed to occur by a post transcriptional mechanism
(Moreno, 1995).
Synergy of carotenoids with xanthophylls and other antioxidants.
A healthy diet of fruit and vegetables results in approximately 19 different carotenes and
xanthophylls being present in human blood and tissues. These and other carotenoids in the
diet have quite different structures and therefore different biological properties. The structure
and properties of carotenes and xanthophylls determines their location and orientation in the
plasma membrane, so that carotenes are embedded deep in the hydrophobic core whilst the
more polar xanthophylls span the membrane (Subczynski, 1992; Gabrielska, 1996). This not
only will affect the properties of the membrane itself but also the possible interaction of these
molecules with other antioxidants and indeed different ROS. A combination of carotenes and
xanthophylls in the plasma membrane may provide optimal protection against free radicals,
for example the carotene lycopene and the xanthophyll lutein act in a synergistic manner to
protect liposomes against oxidative damage (Stahl, 1998).
There is an increasing interest in flavonoids as dietary antioxidants, but little is known of their
in vivo mechanisms or their metabolites. Work by Pietta (1998) suggests that flavonoids may