Carotenoid Uptake and Protection in Cultured RPE - Carotenoids: Physical, Chemical, and Biological Functions and Properties - page 330

Thus it may be suggested that, particularly in AMD, retinal carotenoids are at risk of oxidative
damage. The free radical pathways leading to carotenoid oxidation have been already discussed.
Markedly, while overall singlet oxygen quenching by carotenoids occurs mainly via a physical route
of energy transfer followed by a thermal deactivation of the excited state of carotenoid molecule, a
small fraction of interactions with singlet oxygen do lead to oxidation of carotenoids (Fiedor et al.,
2005; Stratton et al., 1993). Moreover, hypochlorite a potent oxidant, produced under physiological
conditions by activated neutrophils and macrophages, also leads to rapid carotenoid degradation
(Sommerburg et al., 2003).
The degradation of b-carotene has become the subject of extensive studies especially after two
large clinical trials indicated that b-carotene supplementation substantially increased the risk of
lung cancer in smokers and asbestos workers (Albanes et al., 1995; Omenn, 1996; Omenn et al.,
1996). Oxidative degradation of b-carotene induced by free radicals or singlet oxygen leads to the
formation of several different endoperoxides, epoxides, and apo-carotenals, including all- trans -
retinal (Fiedor et al., 2005; Handelman et al., 1991b; Kennedy and Liebler, 1991; McClure and
Liebler, 1995; Mordi et al., 1991, 1993; Sommerburg et al., 2003; Stratton et al., 1993). All- trans -
retinal is a potent photosensitizer that upon photoexcitation with blue light photogenerates singlet
oxygen and free radicals (Rozanowska and Sarna, 2005). These properties indicate that all- trans -
retinal may exert damaging effects upon the retina as a consequence of irradiation with blue light,
an action opposite to protective action of its precursor, b-carotene.
It has been also shown in numerous studies that degradation products of b-carotene can exert
an action opposite to their parent compound and induce damage to biomolecules independent on
light (Klamt et al., 2003; Marques et al., 2004; Murata and Kawanishi, 2000; Siems et al., 2002).
For instance, incubation of retinal, b-apo-8 -deoxyguanosine for

72 h under aerobic conditions leads to the formation of a mutagenic adduct, 1, N 2 -entheno-2

′ -carotenal or b-carotene with 2 ′

-
deoxyguanosine (Marques et al., 2004), and the yields of those adducts are up to 12-fold increased
when hydrogen peroxide is included in the incubation mixture. While b-carotene also leads to the
adduct formation in this assay, it may be argued that under the conditions employed, b-carotene
becomes at least partly degraded to apo-carotenoids by the end of the incubation period.
Nucleic acids are not the only biomolecules susceptible to damage by carotenoid degradation
products. Degradation products of b-carotene have been shown to induce damage to mitochondrial
proteins and lipids (Siems et al., 2002), to inhibit mitochondrial respiration in isolated rat liver mito-
chondria, and to induce uncoupling of oxidative phosphorylation (Siems et al., 2005). Moreover, it
has been demonstrated that the degradation products of b-carotene, which include various alde-
hydes, are more potent inhibitors of Na-K ATPase than 4-hydroxynonenal, an aldehydic product of
lipid peroxidaton (Siems et al., 2000).
Numerous studies have demonstrated that degradation products of b-carotene exhibit deleteri-
ous effects in cellular systems (Alija et al., 2004, 2006; Hurst et al., 2005; Salerno et al., 2005;
Siems et al., 2003). A mixture of b-carotene degradation products exerts pro-apoptotic effects and
cytotoxicity to human neutrophils (Salerno et al., 2005; Siems et al., 2003), and enhances the geno-
toxic effects of oxidative stress in primary rat hepatocytes (Alija et al., 2004, 2006), as well as
dramatically reduces mitochondrial activity in a human leukaemic cell line, K562, and RPE 28
SV4 cell line derived from stably transformed fetal human retinal pigmented epithelial cells (Hurst
et al., 2005). As a result of degradation or enzymatic cleavage of b-carotene, retinoids are formed,
which are powerful modulators of cell proliferation, differentiation, and apoptosis (Blomhoff and
Blomhoff, 2006).
In some studies it was shown that b-carotene decomposes more rapidly than lutein and zeaxan-
thin when exposed to oxidants or light in the presence and absence of rose bengal as a photosensi-
tizer (Hurst et al., 2004; Ojima et al., 1993; Siems et al., 1999). However, it is not a rule, as lutein and
zeaxanthin are depleted faster than b-carotene during methylene blue photosensitized oxidation of
human plasma (Ojima et al., 1993).

′