Lycopene effects on rat normal prostate and prostate tumor tissue.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
Volker Spitzer
Publications and source records attributed to Volker Spitzer.
Lycopene reduced gene expression of steroid targets and inflammatory markers in normal rat prostate.
Epidemiological evidence links consumption of lycopene, the red carotenoid of tomato, to reduced prostate cancer risk. We investigated the effect of lycopene in normal prostate tissue to gain insight into the mechanisms, by which lycopene can contribute to primary prostate cancer prevention. We supplemented young rats with 200 ppm lycopene for up to 8 wk, measured the uptake into individual prostate lobes, and analyzed lycopene-induced gene regulations in dorsal and lateral lobes after 8 wk of supplementation. Lycopene accumulated in all four prostate lobes over time, with all-trans lycopene being the predominant isoform. The lateral lobe showed a significantly higher total lycopene content than the other prostate lobes. Transcriptomics analysis revealed that lycopene treatment mildly but significantly reduced gene expression of androgen-metabolizing enzymes and androgen targets. Moreover, local expression of IGF-I was decreased in the lateral lobe. Lycopene also consistently reduced transcript levels of proinflammatory cytokines, immunoglobulins, and immunoglobulin receptors in the lateral lobe. This indicates that lycopene reduced inflammatory signals in the lateral prostate lobe. In summary, we show for the first time that lycopene reduced local prostatic androgen signaling, IGF-I expression, and basal inflammatory signals in normal prostate tissue. All of these mechanisms can contribute to the epidemiologically observed prostate cancer risk reduction by lycopene.
Androgens↗
Identification of hepatic molecular mechanisms of action of alpha-tocopherol using global gene expression profile analysis in rats.
The recent discovery that vitamin E (VE) regulates gene activity at the transcriptional level indicates that VE may exert part of its biological effects by mechanisms which may be independent of its well-recognised antioxidant function. The objective of this study was the identification of hepatic vitamin E-sensitive genes and examination of the effects of VE on their corresponding biological endpoints. Two groups of male rats were randomly assigned to either a VE-sufficient diet or to a control diet deficient in VE for 290 days. High-density oligonucleotide microarrays comprising over 7000 genes were used to assess the transcriptional response of the liver. Differential gene expression was monitored over a period of 9 months, at four different time-points, and rats were individually profiled. This experimental strategy identified several VE-sensitive genes, which were chronically altered by dietary VE. VE supplementation down-regulated scavenger receptor CD36, coagulation factor IX and 5-alpha-steroid reductase type 1 mRNA levels while hepatic gamma glutamyl-cysteinyl synthetase was significantly up-regulated. Measurement of the corresponding biological endpoints such as activated partial thromboplastin time, plasma dihydrotestosterone and hepatic glutathione substantiated the gene chip data which indicated that dietary VE plays an important role in a range of metabolic processes within the liver.
Animal Feed↗
Lycopene and vitamin E interfere with autocrine/paracrine loops in the Dunning prostate cancer model.
Epidemiological studies have consistently associated high intakes of lycopene or vitamin E with a reduced prostate cancer risk. Both compounds were tested in the MatLyLu Dunning prostate cancer model to gain insight into the in vivo action of lycopene and vitamin E. Supplementation for 4 weeks with 200 ppm lycopene, 540 ppm vitamin E, or both led to plasma levels comparable with those in humans. Both compounds also accumulated in tumor tissue. Macroscopic evaluation of the tumors by magnetic resonance imaging showed a significant increase in necrotic area in the vitamin E and the lycopene treatment groups. Microarray analysis of tumor tissues revealed that both compounds regulated local gene expression. Vitamin E reduced androgen signaling without affecting androgen metabolism. Lycopene interfered with local testosterone activation by down-regulating 5-alpha-reductase and consequently reduced steroid target genes expression (cystatin-related protein 1 and 2, prostatic spermine binding protein, prostatic steroid binding protein C1, C2 and C3 chain, probasin). In addition, lycopene down-regulated prostatic IGF-I and IL-6 expression. Based on these findings, we suggest that lycopene and vitamin E contribute to the reduction of prostate cancer by interfering with internal autocrine or paracrine loops of sex steroid hormone and growth factor activation/synthesis and signaling in the prostate.
Androgens↗
Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin.
BACKGROUND: Zeaxanthin is hypothesized to reduce the risk of age-related macular degeneration; however, kinetic information is limited. OBJECTIVES: The objective was to investigate the plasma kinetics of synthetic zeaxanthin after repeated oral doses and to assess the possible influence of other carotenoids on plasma zeaxanthin concentrations. DESIGN: After a run-in of 3 d, 20 healthy volunteers assigned to 2 parallel dose groups received once daily oral doses of either 1 mg (1.76 micro mol) or 10 mg (17.6 micro mol) zeaxanthin for 42 d. Plasma concentration-time profiles on days 1 and 42, concentrations immediately before zeaxanthin intake during the dosing period, and concentrations after the last dose until day 76 were monitored. RESULTS: all-E-Zeaxanthin concentrations increased from 0.048 +/- 0.026 micro mol/L at baseline to 0.20 +/- 0.07 and 0.92 +/- 0.28 micro mol/L with 1 and 10 mg zeaxanthin, respectively. The dose-normalized bioavailability of all-E-zeaxanthin after the10-mg dose was 40% lower (P < 0.001) than after the 1-mg dose. Other kinetic parameters did not differ significantly between groups. After 17 d of dosing, >90% of steady state concentrations were reached, which was compatible with an effective half-life for accumulation of 5 d. The terminal elimination half-life was 12 +/- 7 d (n = 20). The time course of plasma all-E-3-'dehydro-lutein concentrations resembled that of all-E-zeaxanthin. The data provided evidence that all-E-3-'dehydro-lutein was derived from all-E-zeaxanthin. Concentrations of other carotenoids were not affected. Zeaxanthin was well tolerated. CONCLUSION: Long-term oral intake of 1 and 10 mg zeaxanthin as beadlets increases plasma zeaxanthin concentrations approximately 4- and 20-fold, respectively. Evidence that all-E-3-dehydro-lutein is formed from zeaxanthin was strong.
Administration, Oral↗
Age-related changes of vitamin A status.
Ageing is an independent risk factor for the development of cardiovascular disease. The ageing process is known to be associated with increased oxidative stress and an increased risk for cardiovascular and other diseases, such as cancer. To delay this process, therapeutic strategies involving the use of naturally occurring antioxidants, such as vitamin A, have gained considerable interest. Therefore, we wanted to investigate in a model of mammalian ageing whether changes in tissue and plasma levels of vitamin A occur with increasing age. This would constitute a prime rationale for its dietary supplementation. Experiments were performed in three different age groups (4-6 months old, 19 months old, 32-35 months old) of F1 (F344 x BN) healthy male rats that were fed a normal diet without any additional supplementation. Vitamin A and carotenoids in plasma and major organs were measured by reverse-phase high-performance liquid chromatography. In 3-year-old rats, vitamin A levels were found to be decreased in plasma (P < 0.0001) as compared with young and middle-aged animals. However, they were markedly increased in the main storage organ (ie, the liver) (P < 0.01-0.0001), and also in the aortic vessel wall. They were undetectable in the heart, irrespective of age. Increased tissue levels of vitamin A, especially in the vasculature, may be part of an age-associated self-regulatory process of adaptation, possibly as a counter-regulation against oxidative tissue damage. Based upon the assumption that in elderly humans, as in our animal model, a similar demand-regulated mechanism may work independently of additional dietary vitamin A supplementation, one may question the strategy of large clinical interventional trials using vitamin A or its derivatives beyond normal dietary intake.
Aging↗
Decreased plasma and tissue levels of vitamin C in a rat model of aging: implications for antioxidative defense.
Aging is an independent risk factor for the development of cardiovascular and many other diseases. The aging process is known to be associated with increased oxidative stress, possibly related to an age-inherent loss of antioxidant capacity. Vitamin C is a major naturally occurring antioxidant. Thus, we investigated its role in a rat model of aging. Vitamin C in plasma and tissues as well as malondialdehyde in the heart were measured in young (6 months old) and old (27-30 months old) F1 (F344 x BN) healthy male rats fed a normal diet. In old rats, vitamin C plasma levels were found to be decreased (p<0.02) as compared with young animals. Furthermore, there was a tissue-specific distribution: in the heart, liver, kidney, lungs, and skeletal muscle, vitamin C decreased with age (p<0.005 to p<0.05), while no significant differences could be observed in the aortic wall and in the brain. Organs of the digestive tract rather showed an increase of vitamin C levels with age. Oxidative stress, determined representatively in the heart by measuring malondialdehyde tissue levels, exhibited an age-dependent increase (p<0.05). A distinct pattern of specific tissue distribution of vitamin C suggests a differential age-associated regulation. As vitamin C decreased concomitantly to an increase in cardiac lipid peroxidation, its supplementation may be useful to prevent age-related oxidative stress and tissue aging.
Aging↗
Microwave-assisted rapid determination of vitamins a and e in beverages.
A new rapid procedure for the determination of vitamins A and E in beverages has been developed and validated. Key steps include a microwave-assisted saponification of the sample and a single-step extraction of the vitamins prior to HPLC analysis. All sample preparation steps are carried out consecutively in the same vial. The vitamins are determined using normal-phase (Si-60) HPLC with fluorescence detection. The method is applicable to beverages with a content of all-trans-retinol >0.14 mg/L and/or a content of alpha-tocopherol >1 mg/L. Recoveries determined by spiking experiments ranged from 91.3 to 106.3%. The precision of the method is characterized by relative standard deviations of <2% for alpha-tocopherol and <5% for all-trans-retinol.
Beverages↗
Automated determination of selected water-soluble vitamins in tablets using a bench-top robotic system coupled to reversed-phase (RP-18) HPLC with UV detection.
The determination of folic acid, nicotinamide, nicotinic acid, riboflavin, riboflavin-5'-phosphate, pyridoxine and thiamine in tablets has been successfully automated using a bench-top robotic system (Zymark Tablet Processing Workstation II) coupled to reversed-phase (RP-18) HPLC with UV-detection. The new automated methods have been validated and were found to be applicable in routine analysis for all common types of multivitamin tablets. The precision is exemplified by relative standard deviations of 5.4% for folic acid, 2.1% for nicotinamide, 1.6% for pyridoxine, 0.7% for riboflavin and 1.1% for thiamine using film-coated tablets as sample. Mean recoveries obtained during spiking experiments were in the range of 95.2-103.9%.
Autoanalysis↗
Cardiovascular aging is associated with vitamin E increase.
BACKGROUND: Aging is an independent risk factor for the development of cardiovascular disease. Therefore, therapies to delay vascular aging may have enormous medical consequences. In this context, vitamin E is of particular interest, mainly because of its antioxidative properties. METHODS AND RESULTS: In 3-year-old rats, which are not susceptible to atherosclerosis, vitamin E levels, as measured by reversed-phase high-performance liquid chromatography, were markedly increased both in plasma and in major organs (P<0.01 to P<0.0001). The highest increase (at least 70-fold) was found in the aortic wall. CONCLUSIONS: This unexpected accumulation of vitamin E appears to be a compensatory mechanism that attempts to counterbalance age-associated oxidative stress and that may represent a self-regulatory protective adaptation.
Adaptation, Physiological↗