Carotenoid Uptake and Protection in Cultured RPE - Carotenoids: Physical, Chemical, and Biological Functions and Properties - page 331

While degradation products of carotenoids often exhibit completely different properties from
their parent compounds, they are often similar in their abilities to reduce Fe(III) and undergo
subsequent oxidative degradation (Panzella et al., 2004).
Relatively little is known about metabolic pathways of carotenoids other than b-carotene and
the cellular effects they (and their degradation products) may be responsible for. Several studies
have been performed on lycopene, an acyclic carotenoid, which is believed to protect against pros-
tate cancer. It has been demonstrated that rats fed with a lycopene-enriched diet accumulated a
number of different metabolites in their livers, including the aldehydic products, apo-8 ′ -lycopenal

and apo-12 -lycopenal (Gajic et al., 2006). In two other studies it was shown that lycopene easily

undergoes oxidative cleavage and its oxidation products induce apoptosis in several cancer cell lines
(Kotake-Nara et al., 2002; Nagao, 2004).
However, the metabolic pathways of lutein and zeaxanthin are only beginning to be discovered.
Several derivatives of dietary xanthophylls have been identii ed in the retina, such as 3

′

′ -epilutein,

meso-zeaxanthin, 3 -oxolutein, and 3-methoxyzeaxanthin, and it has been suggested that they

may be formed as a result of nonenzymatic oxidative modii cations (Bernstein et al., 2001, 2002b;
Bhosale et al., 2007b; Khachik et al., 1997). The macula lutea contains predominantly meso-
zeaxanthin (Figure 15.1), which is believed to originate from either oxidative modii cation or
double bond isomerization of dietary lutein (Khachik et al., 1997, 2002).
Because of structural similarities between b-carotene and lutein and zeaxanthin, it may be
expected that as a consequence of the oxidative degradation of these xanthophylls, products analo-
gous to oxidation products of b-carotene will be formed. Indeed, in post mortem of human retinas
two aldehydic products were identii ed, 3-hydroxy-b-ionone and 3-hydroxy-14

′

-apocarotenal, both
are likely derived from oxidative cleavage of lutein or zeaxanthin (Prasain et al., 2005). We have
recently shown that the degradation of lutein in vitro during iron ion-mediated lipid peroxidation in
liposomes yields numerous products that include potent photosensitizers, which, upon absorption
of blue light, photosensitize the generation of singlet oxygen, superoxide, and hydroxyl radicals
(Rozanowski and Rozanowska, 2005). Interestingly, the quantum yield of singlet oxygen generation
by the degradation products of lutein is similar to that of all- trans -retinal.
The susceptibility of carotenoids to degradation is also important with regard to production
and storage of carotenoids in dietary supplements. It needs to be noted that there is often a great
discrepancy between the declared and real content of lutein in commercially available supplements
(Breithaupt and Schlatterer, 2005). In a study of 14 products from local supermarkets and pharma-
cies, seven contained smaller amounts of lutein than specii ed, and varied from 11% to 93% of the
stated values (Breithaupt and Schlatterer, 2005). It may be suspected that part of the xanthophylls
degraded during storage. Carotenoids do not require any special oxidants to undergo degradation.
It is enough to leave carotenoids exposed to air to induce their autooxidative degradation to apo-
carotenals and short-chain carbonyl compounds (Kim, 2004; Kim et al., 2001; Mordi et al., 1991,
1993). It is not clear whether the degradation products of carotenoids are absorbed from the gas-
trointestinal track and, if so, whether they can accumulate in toxic levels in human tissues, such
as the retina. Clearly, this is another area demanding experimental investigation. In particular, it
is of interest to determine the role of RPE in carotenoid protection, the metabolism of carotenoid
oxidation products and the possible ways of their removal from the retina.

′

15.8 PRO-OXIDANT AND CYTOTOXIC EFFECTS OF CAROTENOIDS AND
THEIR DEGRADATION PRODUCTS IN CULTURED RPE CELLS
As mentioned previously, b-carotene oxidation products substantially reduce mitochondrial activ-
ity in an RPE cell line, 28 SV4, derived from fetal human RPE cells (Hurst et al., 2005). In these
experiments b-carotene was degraded in dichloromethane/methanol/water solution by hypochlo-
rite, NaOCl. Exposure of the 28 SV4 cells to a mixture of the degradation products corresponding