The carotenoid group of pigments are ubiquitous in nature and more than 600 different
carotenoids have been identified and characterized [1]. They are responsible for pigmentation
in animals, plants, and microorganisms, but crucially also serve important, often
critical, roles in biological systems. Indeed, in recent years most attention focused
on this group of pigments has concerned understanding their function, especially as
antioxidants. The “core” structural element of carotenoids is a polyene backbone consisting
of a series of conjugated C=C bonds. This particular feature is primarily responsible
for both their pigmenting properties and the ability of many of these compounds to
interact with free radicals and singlet oxygen and therefore act as effective antioxidants.
Modifications to this polyene backbone, altering the number of conjugated double bonds
together with the addition of oxygen functional groups, in turn, alter the reactivity
of carotenoids. Importantly, the function of carotenoids is also substantially affected
by their immediate environment, which, in turn, is dependent on their structure (e.g.,
[2]). This is arguably most evident in photosynthetic systems in higher plants and
algae where xanthophylls are restricted to light-harvesting complexes (performing
both light-capture and photoprotective roles), whilst β-carotene is found in reaction
centers (a protective role) (e.g., [3,4]).
Whilst carotenoids are widely distributed across natural systems, research has largely
concentrated on just a few compounds that are involved in aspects of human health
(notably the dietary compounds β-carotene, lutein, and lycopene) or in photosynthetic
processes in plants and photosynthetic bacteria (e.g., β-carotene, spheroidene, lutein,
violaxanthin, and zeaxanthin). In human health, large-scale epidemiological studies
have demonstrated a strong association between diets rich in fruit and vegetables
(including the “Mediterranean” diet) and reductions in certain diseases, including
some cancers and heart disease [5]. This in turn led to large dietary intervention
studies, some of which explored the use of high doses of β-carotene in smokers and
asbestos workers. Two of the most influential studies were the Beta-Carotene and Retinol
Efficacy Trial (CARET [6]) and the Alpha-Tocopherol Beta-Carotene Cancer Prevention
Trial (ATBC [7]). However, the results from such studies appeared to contradict the
dietary studies that preceded them, highlighting the need to better understand how
carotenoids behave in biological, especially human, systems and, indeed, whether carotenoids
can act as both antioxidants and pro-oxidants under different conditions.
This special issue consists of a set of articles which highlight some of these recent
advances concerning the antioxidant properties of carotenoids, reflecting the wide
range of studies on this fascinating group of natural products. Edge and Truscott
[8] review the most recent work on the interaction between singlet oxygen, free radicals,
and carotenoids and retinoids. Whilst the antioxidant properties of these compounds
are well-known, the article highlights some important, often less well-studied, issues.
Recent research by the authors demonstrates that carotenoids can switch from antioxidant
to pro-oxidant behavior as a function of oxygen concentration. Employing a cell-based
model system, they observed total protection from exposure to high energy γ-radiation
by lycopene at 0% oxygen, but zero protection at 100% oxygen. This may have implications
for the behavour of carotenoids in tissues where different partial pressures of oxygen
are present. The physical “organization” (e.g., the tendency for carotenoids to aggregate
in different solvents) of the carotenoid is an important consideration that affects
its antioxidant abilities, through its interactions with reactive oxygen species themselves
as well as with other antioxidants such as α-tocopherol and vitamin C. The antioxidant
properties of the carotenoid astaxanthin are studied by Focsan et al. [9]. This pigment
is bound to the white muscle of salmonids, imparting the characteristic pink coloration
of the fish, and is found in the pigment-protein complexes of the carapace of a number
of crustacea. Astaxanthin also accumulates in the freshwater microalga Haematococcus
pluvialis under stress conditions (e.g., nutrient deprivation, exposure to high irradiances,
or in the presence of reactive oxygen species). Using a range of techniques including
electron paramagnetic resonance, Foscan and colleagues [9] indicate that a range of
factors influence the antioxidant activity of astaxanthin. These include: the formation
of chelate complexes with metals; esterification and its inability to aggregate in
the ester form; a high oxidation potential; and the formation of neutral radicals
under high irradiation in the presence of metal ions.
As these papers illustrate, there is no doubt that the interaction of carotenoids
with reactive oxidizing species is highly complex. The fate of these carotenoids and
the properties of the resulting reaction products, including geometric isomers, adducts,
and breakdown or cleavage compounds are still relatively poorly understood. In this
special issue, two papers consider separate aspects of this. First, Haider and colleagues
[10] explore the potential genotoxic and cytotoxic roles of oxidative breakdown products
of carotenoids. The pro-oxidant effects resulting from exposure to high doses of carotenoids
seen in vivo (as in the CARET and ATBC trials [6,7]), or enhanced DNA damage seen
in in vitro studies (e.g., [11]) are often associated with the accumulation and subsequent
deleterious actions of a range of putative breakdown products. Haider et al. [10]
found that low doses (1 µM) of cleavage products of β-carotene (generated by hypochlorite
treatment) induced significant levels of DNA strand breaks in primary pneumocyte type
II cells that were subjected to oxidative stress. By contrast, β-carotene itself acted
as an effective antioxidant and cytotoxic effects were only seen at much higher concentrations
(50 μM). The in vivo oxidative generation of geometric isomers of another major dietary
carotenoid, lycopene, is considered by Graham et al. [12]. In vitro studies have demonstrated
that exposure to the complex mixture of free radicals found in cigarette smoke induces
the bleaching of carotenoids, such as lycopene and β-carotene, via a series of reactions
including cleavage and isomerization [13,14]. The detection of such reaction products
in vivo is especially challenging due to their (often) transient nature and trace
levels. Graham et al. [12] found that the plasma of smokers contained elevated proportions
of (13Z)-lycopene relative to the other geometric isomers of this carotenoid. This
finding is consistent with in vitro observations that this particular, energetically-unfavored,
geometric form was preferentially generated in the presence of cigarette smoke [13].
Further work is needed to determine the full range of reaction products of dietary
carotenoids when exposed to reactive oxygen species, elucidate the pathways by which
such degradation occurs, and better understand their possible function.
The role of carotenoids in the human macula is discussed by Gong et al. [15]. The
xanthophylls lutein and zeaxanthin are accumulated within and protect the macula.
This study examined the behavour of three dietary carotenoids, namely, β-carotene,
lycopene, and lutein, in retinal pigment epithelial cells. Lutein and lycopene, but
not β-carotene, inhibited the growth of undifferentiated ARPE-19 cells. Moreover,
cell viability was decreased under hypoxic conditions. It is worthwhile noting that
the macula carotenoids (lutein and zeaxanthin) also have well-defined functional roles
in higher plant photosynthesis, in both light-capture and energy-quenching [3]. The
ability of these molecules to function in plants and humans alike is dependent upon
the same chemical and physical properties.
Carotenoids are widely distributed across the natural world and to reflect this, Galasso
et al. [16] review the occurrence and diversity of carotenoids in the marine environment
as well as their potential for economic exploitation (e.g., as natural sources of
pigments for food and feed industries or as a source of antioxidants). Carotenoids
are recognized as the most common class of pigments in the marine environment, with
a much greater diversity of structures than that seen in the terrestrial environment
[1]. However, beyond a handful of compounds such as astaxanthin and fucoxanthin, they
remain relatively poorly studied. Continuing the economic theme, Fu et al. [17] examine
the distribution of pigments and their antioxidant activities in durum wheat milling
fractions.
In conclusion, carotenoids remain a fascinating group of natural pigments. Not only
are they responsible for a broad array of coloration in nature, but, more importantly,
they have key functional roles in biology. Studies on their function in human health
and disease have all too often focused solely on what might be regarding as a hunt
for a “magic bullet” effect, i.e., a particular carotenoid (e.g., β-carotene) is found
in “healthy” diets and, as it is an antioxidant (at least in vitro), it is assumed
that high doses must have a beneficial effect. Sadly, all too often this approach
has been shown to be far too simplistic, neglecting as it does the interaction with
other dietary components (including other antioxidants) and the fate of the antioxidants
themselves, especially when present at high doses. Whilst some researchers (e.g.,
Truscott and Edge) have always considered some of these aspects, we are now seeing
many more studies tackling these complex and technically challenging issues.