Protective Effects of Carotenoids Related with Their Antioxidant Activity

Reactive molecules (free radicals and singlet oxygen) are generated in the body under normal conditions or as a consequence of external factors. These radicals are highly reactive chemical species that contain one or more unpaired electrons. When the amount of these reactive species exceeds the normal levels in the body, they may

16 Absorption of Carotenoids and Mechanisms Involved in Their Health. . . 419

exert harmful effects, damaging important molecules, such as proteins, DNA, lipids, and carbohydrates, causing an abnormal cell operation and various pathologies (Bramley et al.2000; Stahl and Sies2003). The antioxidant activity of carotenoids has been extensively studied and associated with the conjugate double bonds in the carotenoid structure since it constitutes a reactive electron-rich system susceptible to react with electrophilic compounds (van den Berg et al. 2000). In animal systems, the carotenoid capacity to quench singlet oxygen and peroxyl radicals, deactivate electronically excited sensitizer molecules and filter blue light are of major importance. The three primary chemical reactions to scavenge oxidizing free radicals by carotenoids are electron transfer (CARCROO^•!ROO^!CCAR^•C or ROO^C C CAR^•–), adduct formation (CARCROO^•!ROOCAR^•) and hydrogen atom transfer (CARCROO^•!ROOHCCAR^•) (Böhm et al. 2012; Edge and Truscott, 2010; van den Berg et al. 2000). The physical capacity of carotenoids to inactivate singlet oxygen depends on the number of double bonds in their backbone because of at triplet energy level they are able to receive the excitation energy from the singlet oxygen and then dissipating the energy as heat to the surrounding media, returning to their ground state. The “-carotene, zeaxanthin, cryptoxanthin, and’-carotene are highly active quenchers of singlet oxygen (Edge and Truscott2010; Stahl and Sies2003). Carotenoids can interrupt the production of peroxyl radicals generated during the lipid oxidation. Some harmful carotenoid radicals may be generated as intermediates in peroxidation systems; however, the involved chemical mechanism depends, among other factors, on the reactivity of peroxyl radicals (Edge and Truscott 2010; El-Agamey et al. 2004; van den Berg et al. 2000). The scavenging of peroxyl radicals protects cellular membranes and lipoproteins from oxidative damage (Stahl and Sies2003). The carotenoids protect the long-chain polyunsaturated fatty acids of the retina from the reactive oxygen species generated by the high-energy short wavelength visible light and reduce the formation of lipofuscin (Ma and Lin2010). The carotenoids can be oxidized under some conditions, such as oxidative stress, deficiency of antioxidants or high levels of carotenoids. The “-carotene autooxidation produces epoxy-carotenoids, “-apo- carotenones and“-apo-carotenals, with some of them being precursors of vitamin A (Stahl and Sies2003; van den Berg et al.2000).

Lutein and zeaxanthin are accumulated in the retina and lens within the eye (Ma and Lin2010). They act as filters for the blue light, attenuating in about 40 % the light that reaches photoreceptors, retinal pigment epithelium and choriocapillaris, reducing their damage (Krinsky et al. 2003). Additionally, zeaxanthin and lutein provide protection against photooxidation. High amounts of reactive oxygen species are generated in the retina by the simultaneous exposure to both light and oxygen.

The high content of long-chain polyunsaturated fatty acids in the retina increases their vulnerability to oxidative damage. Thus, xanthophylls inhibit the peroxi- dation of membrane phospholipids and reduce the photooxidation of lipofuscin fluorophores (Schalch et al 2010; Ma and Lin 2010). The lipofuscin is a potent photoinducible generator of reactive oxygen species that has been highly related to the pathogenesis of AMD (Age-related Macula Degeneration). Epidemiological studies have associated the high consumption of lutein and zeaxanthin with reduced

420 B. Cervantes-Paz et al.

risk of AMD (Seddon et al. 1994; Snellen et al. 2002). The intake of lutein has also been associated with a reduced risk for cataracts (Lyle et al. 1999). Gale et al. (2001) reported that the plasma concentration of ’-carotene and “-carotene was negatively correlated with the risk of nuclear cataract, whereas high plasma concentrations of lycopene and lutein reduced the risk of cortical and subcapsular cataract, respectively.

Epidemiological studies have shown that the consumption of carotenoid-rich fruits and vegetables is associated with a lower risk of cardiovascular diseases;

however, other dietary components from fruits and vegetables, like vitamin C, might be responsible of this protective effect (Koh et al. 2011; Ito et al. 2006; Sesso et al. 2004). The main action mechanism of carotenoids in this regard has been associated with their antioxidant activity. Carotenoids scavenge reactive oxygen species (ROS), protecting the low-density lipoproteins from oxidation, a key process in the pathogenesis of atherosclerosis. After the daily consumption of tomato juice (40 mg lycopene), carrot juice (22.3 mg “-carotene) or a liquid spinach powder preparation (11.3 mg lutein) for two weeks, only the tomato juice reduced the lipid peroxidation in LDL of healthy men (Bub et al.2000). Contrarily, in another study the oxidation of LDL was inhibited by “-carotene (15 mg) but not by lycopene supplementation (34 mg) (Dugas et al.1999). Further work is required to evaluate the effect of carotenoids in cardiovascular diseases.

The etiology of rheumatoid arthritis has been strongly associated with a chronic inflammation state, in which the active function of macrophages, monocytes and granulocytes induce the formation of free radicals, which has been found in synovial fluids of patients with rheumatoid arthritis (Cerhan et al.2003; Costenbader et al.

2010; Merry et al. 1989). Thus, dietary antioxidants have been considered in the prevention and treatment of this disease. An epidemiological study reported an inverse relationship between the high intake of “-cryptoxanthin and the risk of rheumatoid arthritis, but any relation was found for other carotenoids such as “- carotene, lycopene or lutein/zeaxanthin (Cerhan et al.2003). Other studies neither could relate the consumption of carotenoids with the prevention of rheumatoid arthritis (Costenbader et al.2010; Heliövaara et al.1994).

The pathogenesis of Alzheimer Disease (AD) has been related with oxidative stress. The brain is particularly susceptible to the oxidation due to its high metabolic activity and demand of oxygen and because it contains abundant amounts of polyunsaturated fatty acids (Mecocci et al. 2002). Jiménez-Jimenéz et al. (1999) reported that AD patients showed low levels of“-carotene and vitamin A. Mecocci et al. (2002) also reported high plasmatic levels of the oxidative indicator 8-hydroxy- 2⁰-deoxyguanosine and low levels of antioxidants (zeaxanthin, “-cryptoxanthin, lycopene, and’-carotene and “-carotene) in AD patients. High levels of phospho- lipid hydroperoxides and amyloid “-peptide (A“) have been reported in the red blood cells of AD patients (Nakagawa et al.2011). Somein vitroandin vivostudies have demonstrated that lutein, astaxanthin and“-carotene decreased the interaction between erythrocytes and A“in cells from human and mice (Nakagawa et al.2011).

The retinoic acid may regulate genes involved in the A“ expression, such as the

“-secretase enzyme, AbPP, and presenilin (Obulesu et al.2011).

16 Absorption of Carotenoids and Mechanisms Involved in Their Health. . . 421