NITRIC OXIDE: Biology and Chemistry Vol. 2, No. 1, pp. 8–16 (1998) Article No. NO970156 The Reaction of Peroxynitrite with Zeaxanthin Romeo Scheidegger, A. K. Pande, Patricia L. Bounds, and W. H. Koppenol 1 Laboratorium fu ¨ r Anorganische Chemie, Eidgeno ¨ssische Technische Hochschule, Universita ¨ tstrasse 6, CH-8092 Zu ¨ rich, Switzerland Received October 29, 1997 approach to prevention, and that dietary carotenoids The oxygenated carotenoids zeaxanthin and lu- may play a role (2). tein, found in the macular area of the retina, may Two carotenoids have been identified in the macu- offer protection against or repair of oxidative dam- lar area of the human retina, the xanthophylls zea- age associated with the degenerative diseases of xanthin and lutein (3, 4). Humans accumulate both aging. Since both superoxide and nitrogen monox- b-carotenes and xanthophylls, oxygenated carot- ide, which react to form peroxynitrite, are found in enoids, in plasma and tissues (5), but zeaxanthin the retina, we studied the reaction of peroxynitrite and lutein appear to be specifically concentrated in with zeaxanthin in liposomes. Zeaxanthin was eas- the macula (2). The biological function of xantho- ily incorporated into liposomes constructed from the fully saturated lipid L-a-dimyristoyl-phosphati- phylls has not yet been clearly established; e.g., com- dylcholine (C14:0) and from egg lecithin, and its ab- pared to b-carotene, xanthophylls have little pro- sorbance spectrum in liposomes strongly resembles vitamin A activity (6). in shape and amplitude that of zeaxanthin dissolved It has been postulated that carotenoids can pre- in methanol. The reaction between peroxynitrite vent cancer and the degenerative diseases associ- and zeaxanthin is first-order in both substrates. The ated with aging, e.g., AMD, by limiting biological pH profile indicates that the reaction with zeaxan- oxidative damage (7). b-Carotene has been shown to thin involves peroxynitrous acid and not the conju- be an effective quencher of singlet oxygen (8), to in- gate anion. We hypothesize that zeaxanthin plays hibit lipid peroxidation in vitro (9) and in vivo (10), a major role in protection of macular tissue from and to enhance the antioxidant activity of a-toco- oxidative damage.  1998 Academic Press pherol (11). While b-carotene (Fig. 1a) is the most extensively studied carotenoid, xanthophylls have also been described as chain-breaking antioxidants Age-related macular degeneration (AMD) 2 is an in peroxyl radical-mediated peroxidation of phos- important and irreversible disease of the retina, phatidylcholine liposomes (12), and zeaxanthin (Fig. leading to severe loss of vision in people over 50 1b) and b-cryptoxanthin have been shown to be more years of age (1). Because no treatment is currently efficient than b-carotene at inhibiting lipid peroxida- known for AMD, it has been suggested that limiting tion in vitro (13). photo-oxidative damage to the retina could be an Reactive oxygen-containing species have long been collectively invoked as the chemical agents responsible for initiation of lipid peroxidation. New 1 To whom correspondence should be addressed. Fax: 41-1-632- findings, however, indicate that much oxidative 1090. E-mail: koppenol@inorg.chem.ethz.ch. 2 Abbreviation used: AMD, age-related macular degeneration. damage can be ascribed to peroxynitrite [systematic 8 1089-8603/98 $25.00 Copyright  1998 by Academic Press All rights of reproduction in any form reserved. AID NO 0156 / am06h$$241 04-02-98 18:29:58 noas AP: NO