Oxidation products, carotenoids

KHACHiK F BEECHER G R and GOLi M B (1992) Separation and identification of carotenoids and their oxidation products in the extracts of human plasma. Anal Chem. 64(18) 2111-22. 

Antioxidant and Prooxidant Actions and Stabilities of Carotenoids In Vitro and In Vivo and Carotenoid Oxidation Products... 

Interestingly, early examples of carotenoid autoxidation in the literature described the influence of lipids and other antioxidants on the autoxidation of carotenoids." " In a stndy by Budowski et al.," the influence of fat was fonnd to be prooxidant. The oxidation of carotenoids was probably not only cansed by molecnlar oxygen bnt also by lipid oxidation products. This now well-known phenomenon called co-oxidation has been stndied in lipid solntions, in aqueons solntions catalyzed by enzymes," and even in food systems in relation to carotenoid oxida-tion." The inflnence of a-tocopherol on the antoxidation of carotenoids was also stndied by Takahashi et al. ° who showed that carotene oxidation was snppressed as... 

As described in the preceding paragraphs, oxidation products of carotenoids can be formed in vitro as a result of their antioxidant or prooxidant actions or after their autoxidation by molecular oxygen. They can also be found in nature, possibly as metabolites of carotenoids. Frequently encountered products are the monoepoxide in 5,6- or 5, 6 -positions and the diepoxide in 5,6 5, 6 positions or rearrangement products creating furanoid cycles in the 5,8 or 5, 8 positions and 5,8 5, 8 positions, respectively. Products like apo-carotenals and apo-carotenones issued from oxidative cleavages are also common oxidation products of carotenoids also found in nature. When the fission occurs on a cyclic bond, the C-40 carbon skeleton is retained and the products are called seco-carotenoids. 

Seventy naturally occurring carotenoid epoxides have been referenced and 43 of them have been fully characterized. These compounds can be formally considered oxidation products as defined above, but they first have the status of carotenoids. They are indeed found in vivo and are possibly biosynthesized from the corresponding non-oxidized carotenoids. If carotenoids containing epoxide functions have been found in humans, the epoxidation reaction has not yet been proven to occur in humans. 

FIGURE 3.3.1 Chemical structures of carotenoid oxidation products occurring in nature. The compound numbers correspond to those cited in Britton, G. et al., Carotenoids Handbook ... 

There are few naturally occurring oxidation products that do not belong to the families of epoxides or apo-carotenoids. One of those is the metabolite of lycopene known as 2,6-cyclo-lycopene-1,5 diol found in human plasma and at lower levels in tomato products. ... 

Carotenoid oxidation products were not only formed from the parent molecules in order to elucidate structure, they were also obtained by partial or total synthesis or by direct oxidation of carotenoid precursors. Thus, apo-8 -lycopenal was synthesized in 1966 more recently, the ozonide of canthaxanthin was obtained by chemical oxidation of canthaxanthin. ... 

The ready availability of carotenoid oxidation products through chemical methods will facilitate their use as standard identification tools in complex media such as biological fluids, and enable in vitro investigation of their biological activity. Moreover, these studies can help reveal the mechanisms by which they can be chemically or biochemically cleaved in vivo. 

In the natural world, carotenoid oxidation products are important mediators presenting different properties. Volatile carotenoid-derived compounds such as noriso-prenoids are well known for their aroma properties. Examples include the cyclic norisoprenoid P-ionone and the non-cyclic pseudoionone or Neral. Carotenoid oxidation products are also important bioactive mediators for plant development, the best-known example being abscisic acid. Apo-carotenoids act as visual and volatile signals to attract pollination and seed dispersal agents in the same way as carotenoids do, but they are also plant defense factors and signaling molecules for the regulation of plant architecture. 

Vitamin A (retinol) and retinoic acid are carotenoid oxidation compounds that are very important for human health. The main functions of retinoids relate to vision and cellular differentiation. With the exception of retinoids, it was only about 10 years ago that other carotenoid oxidation products were first thought to possibly exert biological effects in humans and were implicated in the prevention - or promotion of degenerative diseases. A review on this subject was recently published. ... 

The underlying mechanisms involved in the activities of carotenoid oxidation products are due either to a possible role as precursors of retinoids that would be the active species for positive effects or to their own specific activities. This latter case is illustrated by the activity of non-provitamin A carotenoid oxidation products such as those derived from lycopene. However, biological effects of carotenoid oxidation products other than retinoids are only hypothesized in vivo in humans, which hypothesis has been used as the basic principle to justify in vitro studies of these compounds. 

Different types of apparently beneficial activities have been demonstrated in vitro for carotenoid oxidation products, including induction of gap-junctional communications, " growth inhibition of leukemia and cancer cells, induction of apoptosis... 

Carotenoid oxidation products are also supposed to have detrimental effects in vivo. As mentioned earlier, they are suspected to be involved in the adverse effects of high doses of 3-carotene supplementation in smokers and asbestos workers (CARET and ATBC studies) and in smoke-exposed ferrets. The mechanisms potentially involved have been investigated in vitro. P-Apo-8 -carotenal, an eccennic cleavage oxidation product of P-carotene, was shown to be a strong inducer of CYPlAl in rats, whereas P-carotene was not active. Cytochrome P450 (CYP 450) enzymes thus induced could enhance the activation of carcinogens and the destruction of retinoic acid. ... 

Carotenoid oxidation products, as carotenoids, may exert protective or detrimental effects on human health. Efforts must be made to try to identify them in vivo where they may appear in lower quantities than carotenoids. Studies of abiotic systems can provide great support for their identification and the comprehension of their stability and reactivity. 

Zurcher, M. and Pfander, H., Oxidation of carotenoids II. Ozonides as products of the oxidation of canthaxanthin, Tetrahedron, 55, 2307, 1999. 

The origin of many of the components of black tea aroma has been studied. Aldehydes are produced by catechin quinone oxidation of amino acids. Enzymic oxidation of carotenoids during manufacture generates ionones and their secondary oxidation products such as theaspirone and dihydroactinidolide. Oxidation of linoleic acid is responsible for the formation of trans-2-hexenal.82... 

Baker, D. L. et al. (1999). Reactions of beta-carotene with cigarette smoke oxidants. Identification of carotenoid oxidation products and evaluation of the prooxidant antioxidant effect. Chem. Res. Toxicol. 12(6) 535-543. Bonnie, T. Y. P. and Y. M. Choo (1999). Oxidation and thermal degradation of carotenoids. J. Oil Palm Res. 11(1) 62-78. 

Zurcher, M. et al. (1997). Oxidation of carotenoids-I. Dihydrooxepin derivatives as products of oxidation of canthaxanthin and beta,beta-carotene. Tet. Lett. 38(45) 7853-7856. 

Moreover, carotenoids themselves are very susceptible to oxidative damage and their oxidation products include deleterious aldehydes (Failloux et al., 2003 Hurst et al., 2005 Rozanowski and Rozanowska, 2005 Siems et al., 2000, 2002 Sommerburg et al., 2003). Therefore it is of interest to find out how carotenoids can offer antioxidant protection in cellular systems, how stable the carotenoids are within cells, and what the fate of the carotenoid degradation products is. 

As already mentioned, van Kuijk and colleagues (Kalariya et al., 2008) tested the effects of oxidation products of [i-carotcnc, lutein, and zeaxanthin on the activation of redox-sensitive transcription factors, NF-kB, and AP-1 in cultured ARPE-19 cells. Degradation products of all three carotenoids induced activation of NF-kB and AP-1, and these effects were ameliorated by pretreatment of cells with 1 mM NAC. NF-kB is a major transcription factor that binds to promoter sites of many pro-inflammatory cytokines such as IL-1, IL-6, TNF-a, and iNOS. These results indicate that the degradation products of carotenoids can stimulate a pro-inflammatory pathway. 

Intercellular communication can be affected by different carotenoids and their oxidation products, and opposing effects can be observed depending on their concentrations (Stahl et al., 1998). Carotenoids play a role in the induction and stimulation of intercellular communication via gap junctions, which in turn play an important role in the regulation of cell growth, differentiation, and apoptosis (Tapiero et al., 2004). 

Salerno, C, Crifo, C, Capuozzo, E, Sommerburg, O, Langhans, CD, and Siems, W, 2005. Effect of carotenoid oxidation products on neutrophil viability and function. Biofactors 24, 185-192. 

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