Kati Fröhlich

Lycopene prevents 7-ketocholesterol-induced oxidative stress, cell cycle arrest and apoptosis in human macrophages.

The present study was undertaken to examine whether lycopene is able to counteract 7-ketocholesterol (7-KC)-induced oxidative stress and apoptosis in human macrophages. Human THP-1 macrophages were exposed to 7-KC (10-25 microM) alone and in combination with lycopene (0.5-2 microM), and we monitored changes in cell oxidative status [reactive oxygen species (ROS) production, NOX-4, hsp70 and hsp90 expressions, 8-OHdG formation] and in cell proliferation and apoptosis. After 24 h of treatment, lycopene significantly reduced the increase in ROS production and in 8-OHdG formation induced by the oxysterol in a dose-dependent manner. Moreover, the carotenoid strongly prevented the increase of NOX-4, hsp70 and hsp90 expressions as well as the phosphorylation of the redox-sensitive p38, JNK and ERK1/2 induced by the oxysterol. The attenuation of 7-KC-induced oxidative stress by lycopene coincided with a normalization of cell growth in human macrophages. Lycopene prevented the arrest in G0/G1 phase of cell cycle induced by the oxysterol and counteracted the increased expression of p53 and p21. Concomitantly, it inhibited 7-KC-induced apoptosis, by limiting caspase-3 activation and the modulatory effects of 7-KC on AKT, Bcl-2, Bcl-xL and Bax. Comparing the effects of lycopene, beta-carotene and (5Z)-lycopene on ROS production, cell growth and apoptosis show that lycopene and its isomer were more effective than beta-carotene in counteracting the dangerous effects of 7-KC in human macrophages. Our study suggests that lycopene may act as a potential antiatherogenic agent by preventing 7-KC-induced oxidative stress and apoptosis in human macrophages.

Rosehip -- a "new" source of lycopene?

Lycopene, an efficient antioxidant and singlet oxygen quencher, is mainly delivered within the human diet out of tomatoes and tomato products. Processing liberates this carotenoid from complexes with proteins and thus makes it more bioavailable. Rosehip, a wild fruit which is used more often recently to produce mark, jams and juices, showed remarkable contents of lycopene (12.9-35.2 mg/100 g) with an unexpected isomer pattern.

Effects of ingestion of tomatoes, tomato juice and tomato puree on contents of lycopene isomers, tocopherols and ascorbic acid in human plasma as well as on lycopene isomer pattern

Tomatoes are an important part of the diet. Lycopene, the predominant carotenoid in tomatoes, is hypothesised to mainly mediate the health benefits of tomato products. Anticancer activity of tomato products and lycopene has been suggested by numerous studies. The aim of the present study was to investigate the effect of ingestion of three different tomato-based foodstuffs on plasma contents of lycopene, tocopherols and ascorbic acid. Because isomers of lycopene may have different biological activities, a special interest was to look how the lycopene isomer pattern is changed depending on the matrix of tomato products. Following a 2-week depletion phase volunteers ingested 12.5 mg lycopene/d for 4 weeks comprising tomatoes, tomato juice or tomato purée. The basal levels of lycopene in plasma were comparable for all groups and decreased significantly during the 2 weeks of depletion to approximately half of the basal values. Following intervention, plasma lycopene concentration increased significantly. Conversely, supplementation did not significantly affect levels of tocopherols and ascorbic acid in plasma. Regarding isomers of lycopene, the (Z)-lycopene:(all-E)-lycopene plasma isomer ratio was significantly changed during the study for all groups. A remarkable enrichment of the relative contents of (5Z)-lycopene was observed during the depletion period, which supports the hypothesis that lycopene (Z)-isomers are formed within the human body after ingestion of (all-E)-lycopene. After dietary intervention with lycopene-rich products the isomer ratios returned to those observed at the start of the study. Further investigations will clarify the process of isomerisation in more detail.

Effects of Lycopene on the Initial State of Atherosclerosis in New Zealand White (NZW) Rabbits

Background Lycopene is the main carotenoid in tomatoes, where it is found in high concentrations. Strong epidemiological evidence suggests that lycopene may provide protection against cardiovascular diseases. We therefore studied the effects of lycopene on diet-induced increase in serum lipid levels and the initiation of atherosclerosis in New Zealand White (NZW) rabbits. Methodology/Principal Findings The animals, divided into four groups of 9 animals each, were fed either a standard diet, a high-cholesterol diet containing 0.5% cholesterol, a high-cholesterol diet containing placebo beadlets, or a high-cholesterol diet plus 5 mg/kg body weight/day of lycopene (in the form of lycopene beadlets), for a period of 4 weeks. We found significantly elevated lycopene plasma levels in the animal group treated with lycopene beadlets. Compared to the high-cholesterol and the placebo group, this was associated with a significant reduction of 50% in total cholesterol and LDL cholesterol serum levels in the lycopene group. The amount of cholesteryl ester in the aorta was significantly decreased by lycopene. However, we did not observe a significant decrease in the extent of aortic surface lipid accumulation in the lycopene group. In addition, no differences in the intima-media thickness among groups were observed. Endothelial-dependent and endothelial-independent vasodilation in isolated rabbit aortic and carotid rings did not differ among any of the animal groups. Conclusions Lycopene supplementation for 4 weeks increased lycopene plasma levels in the animals. Although we found strongly reduced total and LDL cholesterol serum levels as well as significantly lower amounts of cholesteryl ester in the aortae in the lycopene-treated group, no significant differences in initial lesions in the aortae were detected.

Lack of effects of tomato products on endothelial function in human subjects: results of a randomised, placebo-controlled cross-over study.

Epidemiological studies suggest that consumption of tomato products reduces the risk of CVD via antioxidant, hypocholesterolaemic and anti-inflammatory mechanisms. Although experimental data also describe beneficial effects on endothelial function, clinical data in human subjects are lacking. To test the hypothesis that tomato ingestion ameliorates endothelial function, we randomised healthy non-smoking postmenopausal women to consume a buttered roll with and without tomato purée (70 g) in a cross-over design. Endothelial-dependent flow-mediated dilation (FMD) and endothelial-independent nitro-mediated dilation of the brachial artery were assessed with high-resolution ultrasound (13 MHz linear array transducer). Acute (24 h) and long-term (7 d) effects were examined after daily consumption of the described meal. Nineteen volunteers completed the protocol and provided technically suitable ultrasound measurement data. Plasma lycopene levels increased from 0·30 (sem 0·04) (baseline) to 0·42 (sem 0·04) and to 0·74 (sem 0·06) μm after 24 h and 7 d, respectively, with tomato purée consumption. These data indicated an effective absorption of the tomato product. However, both acute and long-term tomato purée consumption had no effects on endothelium-dependent or -independent dilation of the brachial artery. In addition, we found no correlation between lycopene plasma levels and FMD. In conclusion, consumption of tomato products associated with a significant increase in plasma lycopene levels had no effects on endothelial function in healthy postmenopausal women.

Macular Xanthophylls and ω-3 Long-Chain Polyunsaturated Fatty Acids in Age-Related Macular Degeneration: A Randomized Trial

IMPORTANCE It has been shown that the functionality of the macula lutea depends on the nutritional uptake of lutein and zeaxanthin and that it is inversely associated with the risk of age-related macular degeneration (AMD). Additionally, ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) may also be protective. OBJECTIVE To investigate the effect of a 12-month intervention with macular xanthophylls and ω-3 LC-PUFAs on xanthophylls and fatty acids in plasma, antioxidant capacity, and optical density of the macular pigment of patients with nonexudative AMD. DESIGN The LUTEGA study was a randomized, double-blind, placebo-controlled, parallel clinical trial that was conducted for 12 months. SETTING University Eye Hospital and Institute of Nutrition, Friedrich Schiller University Jena, Germany. PARTICIPANTS A total of 172 individuals with nonexudative AMD. INTERVENTION Individuals were enrolled and randomly divided as follows: placebo group, group 1 (a capsule containing 10 mg of lutein, 1 mg of zeaxanthin, 100 mg of docosahexaenoic acid, and 30 mg of eicosapentaenoic acid administered each day), and group 2 (same substances but twice the dose used in group 1). One hundred forty-five participants completed the study successfully. MAIN OUTCOME MEASURES Plasma xanthophyll concentrations and fatty acid profiles, optical density of the macular pigment, and antioxidant capacity in plasma (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid [Trolox] equivalent antioxidant capacity and photochemiluminescence). RESULTS The concentrations of the administered carotenoids in plasma as well as the optical density of the macular pigment increased significantly in the groups randomized to receive supplementary macular xanthophylls and ω-3 LC-PUFAs after 1 month of intervention and remained at this level through the end of the study. Use of the double dose resulted in a beneficial alteration of the fatty acid profile in the plasma of patients with AMD in comparison with the dose in group 1. The lipophilic antioxidant capacity in plasma was significantly elevated with the intervention. CONCLUSIONS AND RELEVANCE A supplement containing a fixed combination of lutein, zeaxanthin, and ω-3 LC-PUFAs during 12 months significantly improved plasma antioxidant capacity, circulating macular xanthophyll levels, and the optical density of the macular pigment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00763659.

Lycopene supplementation restores vitamin A deficiency in mice and possesses thereby partial pro-vitamin A activity transmitted via RAR signaling.

SCOPE The aim of this study was to compare if lycopene also possesses pro-vitamin A (VA) activity comparable to known VA derivatives. MATERIALS AND METHODS We used a transgenic retinoic acid response element reporter mouse model (n = 8, per group) for this study, and after the initial wash out of VA using a vitamin A deficient diet (VAD) for 18 weeks, the animals were supplemented further with (a) VAD-fed mice, (b) VAD-fed mice plus retinol (20 mg/kg bw), (c) VAD-fed mice plus β-carotene (40 mg/kg bw), and (d) VAD-fed mice plus lycopene (40 mg/kg bw). Using ex vivo scanning and gene expression analysis of retinoid target and VA marker gene analysis in various organs of these supplemented mice (b, c, d), we found increased luciferase activity and normalized marker and target gene analysis compared to group a. CONCLUSIONS Lycopene can restore VA deficiency and compensate VA for retinoic acid receptor (RAR)-mediated signaling as the major function of VA in the mammalian organism. Lycopene administration can initiate upregulation of RAR-mediated signaling in various organs in VAD-fed animals via potential novel bioactive lycopene metabolites. This indicates that lycopene possesses partial pro-VA activity in mice transmitted via RAR-mediated signaling.

Antioxidant capacity of tomato seed oil in solution and its redox properties in cultured macrophages

The health benefits of tomato seed oil (TSO) have been suggested to be related to its antioxidant activity, although at the moment not much information is available on the antioxidant effects of TSO in biological systems. In this paper, we evaluated the antioxidant capacity of TSO using different spectrophotometrical antioxidant assays (LPSC, FRAP, αTEAC, DPPH). Moreover, we determined the ability of TSO in inhibiting oxidative stress in human cultured macrophages. The peroxyl radical scavenging LPSC assay was the most sensitive assay to detect the antioxidant capacity of the TSO, followed by the DPPH, FRAP, and αTEAC assay. TSO was able to counteract spontaneous and H₂O₂-induced oxidative stress in human macrophages, limiting intracellular ROS production and controlling oxidative stress signaling. In particular, TSO was able to decrease the phosphorylation of the MAPK ERK1/2, JNK, and p-38, activation of the redox-sensitive NF-kB, and expression of the heat shock proteins 70 and 90. When the antioxidant capacity of TSO was compared with that of purified lycopene, inhibition of ROS production by TSO was remarkably higher. This was due to the high content of other antioxidants in TSO, including (5Z)-, (9Z)-, (13Z)-, and (15Z)-lycopene isomers, β-carotene, lutein, γ-tocopherol, and α-tocopherol.