Chemistry Reference
In-Depth Information
Altogether, studies in cultured RPE indicate that lutein and zeaxanthin may provide antioxidant
protection in the RPE but more research is required to determine the exact mechanisms responsible
for the observed protective effects or the lack thereof.
15.6 PRO-OXIDANT EFFECTS OF CAROTENOIDS
It has been shown that carotenoids can act as a pro-oxidant at high oxygen tensions (Burton and
Ingold, 1984). These observations can be explained considering the mechanism of the antioxidant
action of carotenoids. When lipid-derived peroxyl radicals (LOO
•
) react with carotenoids, the
radical adduct formed, [LOO-Car]
•
, is less reactive than the LOO
•
and so carotenoids act as chain
breaking antioxidants in lipid peroxidation (Equation 15.6). However, in the presence of high
concentrations of oxygen, the oxygen molecule can add to [LOO-Car]
•
generating another peroxyl
radical, LOO-Car-OO
•
, which readily propagates lipid peroxidation (Equation 15.7):
•
•
Car
+
LOO
→−
[LOO
Car]
(15.6)
•
•
⎡
LOO
−
Car
⎤
+
O
→−
LOO
Car
−
OO
(15.7)
⎣
⎦
2
This mechanism explains the pro-oxidant behavior of carotenoids observed when oxygen partial
pressures are higher than 150 mmHg (Burton and Ingold, 1984; Palozza et al., 1995, 1997). It is
believed that oxygen tensions encountered under physiological conditions are not high enough to
induce this pro-oxidant action of carotenoids.
It has been shown in many studies that protective effects of carotenoids can be observed only
at small carotenoid concentrations, whereas at high concentrations carotenoids exert pro-oxidant
effects via propagation of free radical damage (Chucair et al., 2007; Lowe et al., 1999; Palozza,
1998, 2001; Young and Lowe, 2001). For example, supplementation of rat retinal photoreceptors
with small concentrations of lutein and zeaxanthin reduces apoptosis in photoreceptors, preserves
mitochondrial potential, and prevents cytochrome
c
release from mitochondria subjected to oxida-
tive stress induced by paraquat or hydrogen peroxide (Chucair et al., 2007). However, this protective
effect has been observed only at low concentrations of xanthophylls, of 0.14 and 0.17 mM for lutein
and zeaxanthin, respectively. Higher concentrations of carotenoids have led to deleterious effects
(Chucair et al., 2007).
Carotenoid-radical adducts, such as LOO-Car-OO
•
, are not the only products of carotenoid-free
radical interactions which may exhibit pro-oxidant properties. Carotenoid cation radicals can be
damaging to biomolecules. It has been shown by pulse radiolysis that Car
•+
can oxidize amino acids
such as tyrosine and cysteine (Burke et al., 2001; Edge et al., 2000a). Carotenoid cation radicals may
be generated as a result of interaction with the nitrogen dioxide radical, NO
2
•
, a product of interac-
tion of nitric oxide with oxygen, both molecules being highly abundant in the retina (Bohm et al.,
1995; Everett et al., 1996) (Equation 15.8):
•
•+
−
(15.8)
Car
+
NO
→ +
Car
NO
2
2
Moreover, carotenoid cation radicals can be formed as a result of oxidation of carotenoids by iron
ions, Fe(III) (Equation 15.9) (Polyakov et al., 2001):
•+
Car
+
Fe(III)
→−
R
Car
+
Fe(II)
(15.9)
It should be stressed that in the RPE transport of iron ions between the photoreceptors and choroidal
blood supply is constantly occurring (He et al., 2007; Wong et al., 2007). Iron is essential for the
proper function and survival of every cell as it serves as a co-factor for vital mitochondrial enzymes.
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