beta-carotene and peroxynitric-acid

Interaction of peroxynitrite, the product of the reaction between nitric oxide and superoxide, with carotenes (lycopene, alpha-carotene, and beta-carotene) and oxocarotenoids (beta-cryptoxanthin, zeaxanthin, and lutein) was studied both in homogeneous solution and in human low-density lipoproteins (LDL). All carotenoids prevented the formation of rhodamine 123 from dihydrorhodamine 123 caused by peroxynitrite, suggesting that the carotenoids react with peroxynitrite. Oxocarotenoids were as effective as biothiols, known scavengers of peroxynitrite, whereas lycopene, alpha-carotene, and beta-carotene exhibited a considerably more pronounced effect. Moreover, peroxynitrite caused a loss of carotenoids in LDL as was revealed by HPLC. The concentration of peroxynitrite causing half-maximal loss of carotenoids in LDL ranged from 13 +/- 3 to 68 +/- 3 microM for lycopene and lutein, respectively. Again, oxocarotenoids were less reactive in this system. A correlation between efficiency of carotenoids in the competitive assay with dihydrorhodamine 123 and the concentration of peroxynitrite causing half-maximal loss of carotenoids in LDL was observed (r(2) = 0.91). These findings suggest that carotenoids can efficiently react with peroxynitrite and perform the role of scavengers of peroxynitrite in vivo.

Topics: Arteriosclerosis; beta Carotene; Carotenoids; Cryptoxanthins; Fluorescent Dyes; Free Radical Scavengers; Humans; In Vitro Techniques; Lipoproteins, LDL; Lutein; Lycopene; Nitrates; Rhodamine 123; Spectrometry, Fluorescence; Xanthophylls; Zeaxanthins

Peroxynitrite is a powerful oxidising and nitrating agent generated in vivo by the combination of nitric oxide and superoxide. Previous studies have shown that on exposure to peroxynitrite, low density lipoprotein (LDL) is modified resulting in both a time- and concentration-dependent change to lipid and protein components. The present investigation highlights the reaction between carotenoids and tocopherols, present within the lipophilic phase of LDL, and peroxynitrite at varying concentrations. It was observed that the carotenoids were consumed by a significantly greater proportion than that of the tocopherols with lycopene (87.2 +/- 11%) being more reactive than beta-carotene (68.2 +/- 5.8%) when exposed to peroxynitrite (50 microM) for 1 min. Among the tocopherols, alpha-tocopherol (54.9 +/- 20.2%) was more extensively depleted than gamma-tocopherol (14.7 +/- 1.09%) at peroxynitrite concentration of 500 microM. It was also observed that peroxynitrite, unlike copper ions, does not lead to significant peroxidation of LDL as determined by the formation of conjugated dienes and thiobarbituric acid-reactive substances.

Topics: beta Carotene; Carotenoids; Copper; Lipid Peroxidation; Lipoproteins, LDL; Lycopene; Molecular Structure; Nitrates; Oxidation-Reduction; Quinones; Vitamin E

The oxygenated carotenoids zeaxanthin and lutein, found in the macular area of the retina, may offer protection against or repair of oxidative damage associated with the degenerative diseases of aging. Since both superoxide and nitrogen monoxide, which react to form peroxynitrite, are found in the retina, we studied the reaction of peroxynitrite with zeaxanthin in liposomes. Zeaxanthin was easily incorporated into liposomes constructed from the fully saturated lipid L-alpha-dimyristoyl-phosphatidylcholine (C14:0) and from egg lecithin, and its absorbance spectrum in liposomes strongly resembles in shape and amplitude that of zeaxanthin dissolved in methanol. The reaction between peroxynitrite and zeaxanthin is first-order in both substrates. The pH profile indicates that the reaction with zeaxanthin involves peroxynitrous acid and not the conjugate anion. We hypothesize that zeaxanthin plays a major role in protection of macular tissue from oxidative damage.

Topics: beta Carotene; Dimyristoylphosphatidylcholine; Freeze Fracturing; Hydrogen-Ion Concentration; Kinetics; Liposomes; Microscopy, Electron; Nitrates; Phosphatidylcholines; Spectrophotometry, Atomic; Xanthophylls; Zeaxanthins

The peroxynitrite anion and the nitrogen dioxide (radical) are important toxic species which can arise in vivo from nitric oxide. Both in vivo and in vitro cell protection is demonstrated for beta-carotene in the presence of vitamin E and vitamin C. A synergistic protection is observed compared to the individual anti-oxidants and this is explained in terms of an electron transfer reaction in which the beta-carotene radical is repaired by vitamin C.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cell Survival; Drug Synergism; Free Radicals; Humans; Jurkat Cells; Lymphocytes; Nitrates; Nitrogen Dioxide; Oxidants; Vitamin E

beta-Carotene absorbed 2 equimolar amounts of NO2 accompanying the complete destruction of beta-carotene. Electron spin resonance study using 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl revealed that no significant amounts of NO were released by the interaction. Nitrogen atoms derived from NO2 were tightly bound to the beta-carotene molecules. Destruction of beta-carotene was inhibited little by alpha-tocopherol and polyunsaturated fatty esters, and slightly by ascorbyl palmitate, indicating that beta-carotene was a more effective scavenger of NO2. ONOOH/ONOO- and 3-morpholinosydononimine similarly destroyed beta-carotene. The results suggest that beta-carotene contributes to the prevention of cytotoxicity and genotoxicity of NO2 and ONOOH/ONOO- derived from NO.

Topics: Amiloride; Ascorbic Acid; beta Carotene; Docosahexaenoic Acids; Electron Spin Resonance Spectroscopy; Free Radical Scavengers; Nitrates; Nitrogen Dioxide; Vitamin E