Astaxanthin and peridinin, two typical carotenoids of marine microalgae, and lycopene were incorporated in phosphatidylcholine multilamellar liposomes and tested as inhibitors of lipid oxidation. Contrarily to peridinin results, astaxanthin strongly reduced lipid damage when the lipoperoxidation promoters-H(2)O(2), tert-butyl hydroperoxide (t-ButOOH) or ascorbate-and Fe(2+):EDTA were added simultaneously to the liposomes. In order to check if the antioxidant activity of carotenoids was also related to their effect on membrane permeability, the peroxidation processes were initiated by adding the promoters to Fe(2+)-loaded liposomes (encapsulated in the inner aqueous solution). Despite that the rigidifying effect of carotenoids in membranes was not directly measured here, peridinin probably has decreased membrane permeability to initiators (t-ButOOH>ascorbate>H(2)O(2)) since its incorporation limited oxidative damage on iron-liposomes. On the other hand, the antioxidant activity of astaxanthin in iron-containing vesicles might be derived from its known rigidifying effect and the inherent scavenging ability.

Helicobacter pylori infection in humans is associated with chronic type B gastritis, peptic ulcer disease, and gastric carcinoma. A high intake of carotenoids and vitamin C has been proposed to prevent development of gastric malignancies. The aim of this study was to explore if the microalga Haematococcus pluvialis rich in the carotenoid astaxanthin and vitamin C can inhibit experimental H. pylori infection in a BALB/cA mouse model. Six-week-old BALB/cA mice were infected with the mouse-passaged H. pylori strain 119/95. At 2 weeks postinoculation mice were treated orally once daily for 10 days (i) with different doses of algal meal rich in astaxanthin (0.4, 2, and 4 g/kg of body weight, with the astaxanthin content at 10, 50, and 100 mg/kg, respectively), (ii) with a control meal (algal meal without astaxanthin, 4 g/kg), or (iii) with vitamin C (400 mg/kg). Five mice from each group were sacrificed 1 day after the cessation of treatment, and the other five animals were sacrificed 10 days after the cessation of treatment. Culture of H. pylori and determination of the inflammation score of the gastric mucosae were used to determine the outcome of the treatment. Mice treated with astaxanthin-rich algal meal or vitamin C showed significantly lower colonization levels and lower inflammation scores than those of untreated or control-meal-treated animals at 1 day and 10 days after the cessation of treatment. Lipid peroxidation was significantly decreased in mice treated with the astaxanthin-rich algal meal and vitamin C compared with that of animals not treated or treated with the control meal. Both astaxanthin-rich algal meal and vitamin C showed an inhibitory effect on H. pylori growth in vitro. In conclusion, antioxidants may be a new strategy for treating H. pylori infection in humans.

The purpose of the present study was to find out whether co-treatment of human neutrophils with high glucose and methylglyoxal (MGO) can alter the biochemical parameters of human neutrophils. We also examined if astaxanthin associated with vitamin C can improve those biochemical parameters. Neutrophils from healthy subjects were treated with 20 mM of glucose and 30μM MGO followed or not by the addition of the antioxidants astaxanthin (2 μM) and vitamin C (100 μM). MGO/high glucose treatment reduced the phagocytic capacity and the G6PDH, total/SOD and GR activities. Additionally, there was an increase in the activity of myeloperoxidase (MPO) with consequentincrease in the hypochlorous acid production, CAT activity and in the release of IL-6 cytokine without changes in intracellular calcium mobilization. Our study also shows that the association of astaxanthin with vitamin C greatly improved neutrophil phagocytic capacity, decreasing all reactive oxygen species measured, pro-inflammatory IL-1β and TNF-α release, MPO activity and HClO production. The combination of astaxanthin with vitamin C alone has more antioxidant and anti-inflammatory effects than when they were in the presence of MGO/high glucose. Injury to the function of neutrophils dueto high glucose and methylglyoxal appears not to involve oxidative stress or calcium release. The association of antioxidants astaxanthin and vitamin C promoted a significant improvement in the function of neutrophils and in the redox status.

OBJECTIVE:To evaluate the influence of short-term carotenoid and antioxidant supplementation on retinal function in nonadvanced age-related macular degeneration (AMD).

DESIGN:Randomized controlled trial.

PARTICIPANTS:Twenty-seven patients with nonadvanced AMD and visual acuity>or =0.2 logarithm of the minimum angle of resolution were enrolled and randomly divided into 2 age-similar groups: 15 patients had oral supplementation of vitamin C (180 mg), vitamin E (30 mg), zinc (22.5 mg), copper (1 mg), lutein (10 mg), zeaxanthin (1 mg), and astaxanthin (4 mg) (AZYR SIFI, Catania, Italy) daily for 12 months (treated AMD [T-AMD] group; mean age, 69.4+/-4.31 years; 15 eyes); 12 patients had no dietary supplementation during the same period (nontreated AMD [NT-AMD] group; mean age, 69.7+/-6.23 years; 12 eyes). At baseline, they were compared with 15 age-similar healthy controls.

METHODS:Multifocal electroretinograms in response to 61 M-stimuli presented to the central 20 degrees of the visual field were assessed in pretreatment (baseline) conditions and, in nonadvanced AMD patients, after 6 and 12 months.

MAIN OUTCOME MEASURES:Multifocal electroretinogram response amplitude densities (RAD, nanovolt/deg(2)) of the N1-P1 component of first-order binary kernels measured from 5 retinal eccentricity areas between the fovea and midperiphery: 0 degrees to 2.5 degrees (R1), 2.5 degrees to 5 degrees (R2), 5 degrees to 10 degrees (R3), 10 degrees to 15 degrees (R4), and 15 degrees to 20 degrees (R5).

RESULTS:At baseline, we observed highly significant reductions of N1-P1 RADs of R1 and R2 in T-AMD and NT-AMD patients when compared with healthy controls (1-way analysis of variance P<0.01). N1-P1 RADs of R3-R5 observed in T-AMD and NT-AMD were not significantly different (P>0.05) from controls. No significant differences (P>0.05) were observed in N1-P1 RADs of R1-R5 between T-AMD and NT-AMD at baseline. After 6 and 12 months of treatment, T-AMD eyes showed highly significant increases in N1-P1 RADs of R1 and R2 (P<0.01), whereas no significant (P>0.05) change was observed in N1-P1 RADs of R3-R5. No significant (P>0.05) changes were found in N1-P1 RADs of R1-R5 in NT-AMD eyes.

CONCLUSIONS:In nonadvanced AMD eyes, a selective dysfunction in the central retina (0 degrees -5 degrees ) can be improved by the supplementation with carotenoids and antioxidants. No functional changes are present in the more peripheral (5 degrees -20 degrees ) retinal areas.

Astaxanthin (Asx), one of the carotenoids, is a red pigment in fish and Crustaceans, and possesses stronger reduction properties than conventional carotenoids, like beta-carotene. However, little is known about the biochemical properties and physiological functions of astaxanthin. The effects of astaxanthin and vitamin C on stressed rats were studied physiologically and biochemically. beta-Carotene and three kinds of astaxanthins, which were extracted from Haematococcus and Phaffia, and synthesized chemically, were used in these experiments. These rats given astaxanthins or beta-carotene had stress induced on the 12th day by immersing the rats in chest-level water at 20 degrees C for 24 h after fasting for 24 h. Rats given astaxanthins or beta-carotene prior to stressing were appreciably protected against the evolution of gastric ulcerations in relation to control rats. Ulcer indexes in particular were smaller with the rat group fed astaxanthin extracted from Haematococcus than the other groups. Next, the effects of Asx and/or vitamin C on the protection of evolution of gastric ulcer in stressed rats were persued by the same methods as described above. The results showed that rats given Asx or vitamin C were appreciably protected against the evolution of gastric ulcerations in relation to control rats. The effects were more intense, especially in rats simultaneously supplied Asx and vitamin C than in rats taking either Asx or vitamin C. It was suggested that the simultaneous supplementation of food substances with astaxanthin and vitamin C would supply enough antioxidants to offset stress-related injuries.

The chemopreventive action of carotenoids on proteinuria and lymphadenopathy were examined in autoimmune-prone MRL-lpr/lpr (MRL/l) mice. They were fed a synthetic full-fed diet (16-18 kcal/mouse/day) with supplementation of beta-carotene or astaxanthin (0.19 mumoles/mouse, 3 times a week), and the development of lymphadenopathy and proteinuria were examined. MRL/l mice fed a full-fed diet without the supplementation of carotenoids or those fed a calorie-restricted (CR) diet (10-11 kcal/mouse/day, 60% calorie intake of full-fed mice) were employed as controls. CR dramatically delayed the development of proteinuria and lymphadenopathy, as reported previously. Carotenoids also significantly delayed the onset of these symptoms in MRL/l mice fed a full-fed diet. Carotenoids were half as effective as CR and astaxanthin, a carotenoid without provitamin A activity, which appeared to exert more significant preventive actions than beta-carotene in delaying the development of these symptoms. Similar chemopreventive actions of carotenoids were also demonstrated in MRL/l mice fed a regular diet (Lab Chow). CR has been shown to augment IL-2 production and to decrease serum prolactin levels in this strain, which may be related to its dramatic preventive action of autoimmunity. However, carotenoids did not affect IL-2 production nor prolactin levels in full-fed MRL/l mice. The chemopreventive actions of carotenoids observed in autoimmune-prone MRL/l mice may be attributed to yet unknown mechanisms, apart from their provitamin A activity or oxygen-quenching activity.

In this study, combinations of Ginkgo biloba leaf extract (EGb761) plus the carotenoid antioxidant astaxanthin (ASX) and vitamin C were evaluated for a summative dose effect in the inhibition of asthma-associated inflammation in asthmatic guinea-pigs. Ovalbumin-sensitized Hartley guinea-pigs challenged with ovalbumin aerosol to induce asthma, were administered EGb761, ASX, vitamin C or ibuprofen. Following killing, bronchoalveolar lavage (BAL) fluid was evaluated for inflammatory cell infiltrates and lung tissue cyclic nucleotide content. Each parameter measured was significantly altered to a greater degree by drug combinations, than by each component acting independently. An optimal combination was identified that included astaxanthin (10 mg/kg), vitamin C (200 mg/kg) and EGb761 (10 mg/kg), resulting in counts of eosinophils and neutrophils each 1.6-fold lower; macrophages 1.8-fold lower, cAMP 1.4-fold higher; and cGMP 2.04-fold higher than levels in untreated, asthmatic animals (p<0.05). In conclusion, EGb761, ASX and vitamin C are shown here to interact summatively to suppress inflammation with efficacy equal to or better than ibuprofen, a widely used non-steroidal antiinflammatory drug (NSAID). Such combinations of non-toxic phytochemicals constitute powerful tools for the prevention of onset of acute and chronic inflammatory disease if consumed regularly by healthy individuals; and may also augment the effectiveness of therapy for those with established illness.