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Apo-8'-lycopenal and apo-12'-lycopenal are metabolic products of lycopene in rat liver.

The health benefits of lycopene as an anticarcinogenic compound have been widely studied but little is known about the metabolic products of lycopene produced in vivo. We investigated lycopene metabolites in the liver of F344 male rats that had been prefed a lycopene-containing diet (0.25 g lycopene/kg diet). After 30 d of feeding, they were given a single oral dose of 14C-labeled lycopene (421.8 kBq). The metabolic products of both nonradioactive and 14C-labeled lycopene in rat liver were extracted and separated using HPLC and analyzed by UV/VIS spectrometry, online radioactive detection, and off-line and in-line positive ion electrospray ionization MS. Among a number of metabolite products formed, we identified apo-8'-lycopenal (lambdamax = 473 nm and m/z = 417). The putative compound, apo-12'-lycopenal, was detected but no apo-10'-lycopenal was present. A number of other very polar, short-chain and/or short chromophore compounds with UV/VIS absorption <300 nm were present but were not characterized. These data show that lycopene is cleaved in vivo by rats at different positions to produce apo-12'-lycopenal, and other unidentified metabolites in addition to apo-8'-lycopenal. Apo-8'-lycopenal and the putative apo-12'-lycopenal are identified as lycopene metabolites in rat liver in vivo.

Aldehydes↗

Chronic ingestion of lycopene-rich tomato juice or lycopene supplements significantly increases plasma concentrations of lycopene and related tomato carotenoids in humans.

The bioavailability of lycopene from tomato juice and 2 dietary supplements, each containing 70-75 mg lycopene, was studied in 15 healthy volunteers in a randomized, crossover design. Subjects ingested lycopene-rich tomato juice, tomato oleoresin, lycopene beadlets, and a placebo for 4 wk each while consuming self-selected diets. Treatment periods were separated by 6-wk washout periods. Plasma lycopene concentrations, assessed at baseline and weekly throughout the treatment periods, were significantly higher during tomato juice, oleoresin, and lycopene beadlet ingestion than during placebo ingestion. Mean (+/-SEM) increases in plasma lycopene at week 4 of tomato juice, oleoresin, and lycopene beadlet ingestion were not significantly different: 0.24 +/- 0.07, 0.23 +/- 0.05, and 0.24 +/- 0.06 micromol/L, respectively. Plasma concentrations of phytofluene and phytoene, which were present in small amounts in tomato juice, oleoresin, and lycopene beadlets, increased significantly with ingestion of these 3 products. Beta-carotene, zeta-carotene, and 2,6-cyclolycopene-1,5-diol (a metabolite of lycopene)--also present in tomato juice and supplements--were significantly increased with consumption of the tomato juice and lycopene beadlets, but not with oleoresin consumption. A marked increase in plasma concentrations of an unknown compound was observed; it was detected in trace amounts in tomato juice, oleoresin, and lycopene beadlets, and had a maximum absorbance at 448 nm and a molecular weight of 556. Concentrations of plasma lycopene and other carotenoids with potential for enhancing human health can be increased by ingestion of realistic amounts of tomato juice. Lycopene appears to be equally bioavailable from tomato juice and the supplements used in this study.

Adult↗

Tissue lycopene concentrations and isomer patterns are affected by androgen status and dietary lycopene concentration in male F344 rats.

Diets rich in lycopene from tomato products as well as greater concentrations of blood lycopene have been associated with a decreased risk for prostate cancer in epidemiologic studies. However, little is known about factors modulating lycopene absorption, metabolism and tissue distribution in humans and animal models of prostate cancer. A 2 x 4 factorial design was used to measure the effects of androgen status (castrated vs. intact), dietary lycopene concentration (0.00-5.00 g/kg lycopene) and their interaction on tissue lycopene accumulation and isomer patterns in male F344 rats. Male F344 rats ( 14 wk old; 44 castrated, 44 intact) were randomly assigned to one of four diets containing total lycopene concentrations of 0.00, 0.05, 0.50 or 5.00 g/kg as beadlets and fed for 8 wk. Tissue total lycopene and cis/trans lycopene profiles were determined by HPLC. Tissue and serum lycopene concentrations increased significantly (P < 0.01) as dietary lycopene levels increased between 0.00 and 0.50 g/kg. No further increases in serum or tissue concentrations were seen in rats fed dietary lycopene between 0.50 and 5.00 g/kg. As dietary lycopene increased, so did the percentage of cis lycopene in the liver (P < 0.05), due primarily to an increase in the 5-cis isomer. Castrated rats accumulated twice (P < 0.01) the liver lycopene as compared to intact controls, with no effect of castration on serum lycopene or adrenal, kidney, adipose, or lung tissue concentration. Livers from castrated rats had a greater proportion of cis-lycopene than those of intact rats (P < 0.05). A significant interaction between dietary lycopene concentration and androgen status was seen for liver lycopene concentration (P < 0.01). We conclude that serum and tissue lycopene reaches a plateau between 0.05 and 0.50 g/kg dietary lycopene, the tissue cis/trans lycopene ratio increases with greater dietary lycopene and androgens modulate hepatic lycopene metabolism.

Analysis of Variance↗

Comparative multiple dose plasma kinetics of lycopene administered in tomato juice, tomato soup or lycopene tablets.

BACKGROUND: Lycopene is mainly provided in tomato and tomato products in Western diet. Among other factors the systemic availability of lycopene from natural sources is dependent on release from the cell matrix as achieved by food processing. AIMS OF THE STUDY: The purpose of this study was to compare plasma concentration responses of total lycopene and its major isomers to dosing of the carotenoid as tomato juice, tomato soup or tablets containing synthetic lycopene. METHODS: Intake of lycopene rich food products was restricted throughout this randomized, parallel group study, including 6 volunteers per group. Following a 14 day lycopene depletion phase subjects ingested 20 mg of lycopene daily for 8 days as tomato juice, soup prepared from tomato paste or lycopene tablets. Lycopene plasma concentrations were monitored throughout the depletion and dosing phases and for 22 days post-dosing and kinetics were evaluated using both empirical and compartmental modelling. RESULTS: Irrespective of the lycopene treatment all-E lycopene was the predominant lycopene isomer, whereas 5-Z lycopene was the most abundant Z isomer. Plasma concentration response of total and all-E lycopene to dosing of the carotenoid in tablets and tomato soup was comparable but exceeded that of intake in tomato juice. No differences were noted in dose normalized 5-Z lycopene concentrations between groups. The estimates of efficient half-life were approximately 5 and 9 days for all-E and 5-Z lycopene, respectively. CONCLUSIONS: The systemic availability of synthetic lycopene from a tablet formulation is comparable to that observed from processed tomatoes (soup from tomato paste) and superior to that from tomato juice. No differences were observed in disposition kinetics of natural and synthetic lycopene. The synthetic lycopene tablet formulation used in this investigation may be of value for future clinical investigations.

Adolescent↗

Cis-lycopene is more bioavailable than trans-lycopene in vitro and in vivo in lymph-cannulated ferrets.

Lycopene is the predominant carotenoid in tomatoes and tomato-based foods and is also a predominant carotenoid in human serum and tissues. Intake of lycopene-rich foods was recently associated with decreased risk for several chronic diseases. The observation that serum and tissue lycopene is more than 50% cis-lycopene, whereas tomatoes and tomato-based foods contain mainly all-trans-lycopene, has led to the hypothesis that cis-isomers of lycopene are more bioavailable. We tested this hypothesis both in vitro (study 1) and in vivo (study 2). In study 1, bile acid micelles containing crystalline lycopene were prepared. The crystalline lycopene used for these analyses was 54.4% cis-lycopene. The optically clear micelle preparation contained 75.9% cis-lycopene in repeated analyses. In study 2, mesenteric lymph duct cannulated ferrets were used to study the in vivo absorption of lycopene from LycoredTM (an ethyl acetate extract of tomatoes containing 5% lycopene by weight; of which 91% was all-trans lycopene). Before being anesthetized, male ferrets (n = 7) were dosed orally with 40 mg lycopene per kg body weight in soybean oil. Lymph secretions were collected, on ice, for 2 h. The residual stomach and small intestinal contents, mucosa lining, lymph secretion and serum were analyzed by HPLC. Whereas the dose, stomach and intestinal contents contained 6.2-17.5% cis-lycopene, the mesenteric lymph secretions contained significantly more, 77.4%, cis-lycopene (P < 0.01). These studies demonstrate that in ferrets, cis-isomers of lycopene are more bioavailable than trans-lycopene probably because cis-isomers are more soluble in bile acid micelles and may be preferentially incorporated into chylomicrons.

Animals↗

Plasma lycopene concentrations in humans are determined by lycopene intake, plasma cholesterol concentrations and selected demographic factors.

Higher plasma lycopene concentrations have been associated with a reduced risk of several chronic diseases. Determinants of lycopene concentrations in humans have received limited attention. We had blood lycopene concentrations and lycopene consumption data available from 111 participants in a two-center cancer prevention trial involving beta-carotene and examined determinants of plasma lycopene levels cross-sectionally. The median plasma lycopene level was 0.59 micromol/L (range 0.07-1.79). Low plasma concentrations of lycopene were associated with the following variables in univariate analyses: study site (Florida lower than Connecticut, P = 0.001), being nonmarried (P = 0.02), having lower income (P = 0.003), being nonwhite race/ethnicity (P = 0.03), having lower dietary lycopene intake (r = 0.29, P = 0.002), having lower plasma cholesterol (r = 0. 43, P = 0.0001) and triglyceride levels (r = 0.26, P = 0.005), and consuming less vitamin C (r = 0.20, P = 0.03). Women had slightly higher plasma lycopene levels than men (0.65 vs. 0.58 micromol/L; P = 0.31), despite lower dietary intake of lycopene (1,040 vs. 1,320 microg/d; P = 0.50). Plasma lycopene levels did not differ in smokers and nonsmokers. In stepwise regression analyses, the determinants of plasma lycopene were plasma cholesterol, dietary lycopene, and marital status; these three variables explained 26% of the variance in plasma lycopene. Relatively few lifestyle and demographic factors were important determinants of plasma lycopene levels, with plasma cholesterol, marital status, and lycopene intake being of greatest importance.

Adult↗

Effects of ingestion of tomatoes, tomato juice and tomato purée 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.

Adult↗

Lycopene and beta-carotene are bioavailable from lycopene 'red' carrots in humans.

OBJECTIVE: The purpose of this study was to determine if lycopene and beta-carotene are bioavailable from lycopene red carrots and if lycopene absorption is affected by carrot fiber. DESIGN: Two crossover studies in humans attempted to compare the relative bioavailability of lycopene and beta-carotene from tomato paste to a genetically selected lycopene red carrot during chronic feeding. Each study contained three treatment groups. The vehicle of administration was muffins. INTERVENTION AND METHODS: Study 1 (n=9) used white carrots (0 mg lycopene/day), red carrots (5 mg/day), and tomato paste (20 mg/day). Study 2 (n=10) used red carrots (2.6 mg/day), tomato paste (5 mg/day), and tomato paste plus white carrots (5 mg/day). Each intervention lasted 11 days with a 10-day washout period between treatments. Serum lycopene and beta-carotene were measured by HPLC. RESULTS: Statistical analysis indicated a significant effect of muffin type in study 1 (P<0.001), and a significant treatment by sequence interaction in study 2 (P=0.04). The response to increasing amounts of lycopene is linear at the levels fed in these studies (r=0.94). The data suggest that maintenance of serum lycopene concentrations at 0.3 micromol/l occurs at about 2 mg/day of lycopene from mixed dietary sources and a serum plateau occurs at >/=20 mg/day. CONCLUSIONS: These results show that lycopene and beta-carotene are bioavailable from red carrots and lycopene absorption seems to be affected by carrot fiber. Making inferences from both studies, the lycopene in the red carrot is about 44% as bioavailable as that from tomato paste. Red carrots provide an alternative to tomato paste as a good dietary source of lycopene and also provide bioavailable beta-carotene.

Adult↗

Ingestion by men of a combined dose of beta-carotene and lycopene does not affect the absorption of beta-carotene but improves that of lycopene.

A double-blind study was conducted in 10 healthy men to investigate serum beta-carotene and lycopene responses after ingestion of individual and combined doses of beta-carotene (BC) and lycopene. On each dosing day, a baseline blood sample was drawn, followed by an oral dose of 0.11 mmol (60 mg) of either all-trans BC or all-trans lycopene or by a combined oral dose of 0.11 mmol each. Subjects were tested with each of the three doses. The dose type was randomized. Blood (10 mL) was drawn at 1, 3, 5, 7, 9, 12 and 24 h after dosing. At 2 and 4 wk after the first dose, the protocol was repeated with the other doses. After ingestion of the BC dose, serum BC concentrations significantly decreased from baseline at 1 and 3 h followed by a continuous increase from baseline that was significant at 12 and 24 h (P < 0.01). Serum lycopene concentrations significantly increased from baseline at 5 h after the lycopene dose (P < 0.008) and returned to baseline thereafter. Ingestion of a combined dose of BC and lycopene resulted in a significant increase in serum concentrations of both BC and lycopene at 24 h (P < 0.05). The 24-h area under the curve (AUC) for BC was not different when BC was ingested alone or with lycopene, whereas the 24-h AUC for lycopene was significantly greater when lycopene was ingested with BC than when ingested alone (P < 0.05). Our data suggest that ingestion of a combined dose of BC and lycopene has little effect on the absorption of BC but improves that of lycopene in men.

Administration, Oral↗

Tissue distribution of lycopene in ferrets and rats after lycopene supplementation.

To determine lycopene uptake and tissue distribution in ferrets (Mustela putorius furo) and F344 rats, we supplemented orally 4.6 mg/(kg body wt.d) lycopene in a tomato oleoresin-corn oil mixture (experimental groups). After 9 wk of supplementation, the animals were killed and blood and organs were collected. Plasma and tissue carotenoids were extracted and measured using HPLC. Mean concentrations of lycopene (nmol/kg wet tissue) in saponified tissues of ferrets were as follows: liver 933, intestine 73, prostate 12.7 and stomach 9.3. Levels of lycopene (nmol/kg wet tissue) in saponified tissue of rats were as follows: liver 14213, intestine 3125, stomach 78.6, prostate 24 and testis 3.9. When these organs were extracted without saponification, the lycopene levels were lower, except for rat testis. All-trans-lycopene was the predominant isomer found in tomato oleoresin and in the majority of rat tissues, whereas cis-lycopenes were predominant in rat prostate and plasma. This pattern was reversed in ferrets. The results show the following: 1) lycopene from tomato oleoresin is absorbed and stored primarily in the liver of both animals; 2) saponification generally improves the extraction of lycopene from most tissues of both animals; 3) cis-lycopene and all-trans-lycopene are the predominant isomers in ferret and rat tissues, respectively; and 4) rats absorb lycopene more effectively than ferrets.

Administration, Oral↗

Novel lycopene metabolites are detectable in plasma of preruminant calves after lycopene supplementation.

Appropriate animal models such as preruminant calves are necessary to study the complex physiological functions of carotenoids and to relate them to possible health effects in humans. In this study, the bioavailability and metabolism of lycopene from 2 dietary supplements were compared. LycoVit containing synthetic lycopene and Lyc-O-Mato containing natural tomato oleoresin were administered to 2 groups of preruminant calves (each n = 8) for 14 d in daily doses of 15 mg of lycopene. Plasma was analyzed for carotenoids before the intervention period, directly after, and each day for 5 d after the end of the intervention. All-trans and 5-cis lycopene, and 3 lycopene metabolites not previously found in calf plasma were detected. These metabolites contributed 52% of the total lycopene content measured at the end of the intervention period. Based on spectroscopic data, they might be hydrogenation products, which are formed from all-trans and/or 5-cis lycopene. In the LycoVit group, total lycopene concentrations were approximately 300% higher (286 +/- 89 nmol/L) than in the Lyc-O-Mato group (72 +/- 33 nmol/L) (P < 0.001). This indicates that, unlike in humans, lycopene from LycoVit and Lyc-O-Mato does not have equal bioavailabilities in preruminant calves. Therefore, the preruminant calf may not be a suitable animal model with which to study the biological and physiological effects of lycopene.

Animals↗

[Factors influencing lycopene content of foods, and lycopene intake of Hungarian population].

Lycopene is an acyclic, biologically active carotenoid that constitutes foods, its preventive role in several cancerous diseases have been proved by epidemiological and experimental data. Its beneficial role in maintenance of human health is related to its significant antioxidant properties. Data of dietary lycopene intake of the Hungarian population is not available. The aims of the present complex study were 1) to measure the lycopene content of foods frequently consumed in Hungary, 2) to investigate the effect of agrotechnological procedures and food processing on lycopene content of tomatoes, 3) to estimate the lycopene intake in two groups of the Hungarian population with the use of a three-day dietary record. The best lycopene sources are the raw (5.0-16.0 mg/100 g) and processed tomatoes and tomato products (3.0-80.0 mg/100 g), and also watermelon (3.6-6.2 mg/100 g). The variety of the plants, the growing circumstances, and the weather conditions significantly influence the lycopene content of freshly consumed and processed tomato fruits. Mild technological processes can preserve a considerable amount of the original lycopene content in tomato. The estimated average dietary intakes of the Hungarian children (n=521) and adults (n=205) were 2.98 +/- 4.71 mg/day/capita, and 4.24 +/- 8.47 mg/day/capita, respectively. Optimal climate conditions of Hungary makes possible to produce tomato fruits with high dietary value including significant amount of health protective lycopene. Increased consumption of tomato and tomato products with high concentration of lycopene may improve the antioxidant capacity of human body, and the risk of several cancerous diseases may be reduced.

Antioxidants↗

Single-dose pharmacokinetic study of lycopene delivered in a well-defined food-based lycopene delivery system (tomato paste-oil mixture) in healthy adult male subjects.

This report details the findings of a single-dose Phase I pharmacokinetic and toxicity study of a food-based formulation of lycopene in healthy adult male subjects. Five dosing groups (n = 5 per group) were sequentially treated with increasing doses of lycopene ranging from 10 to 120 mg. Blood samples were collected for a total of 28 days (672 h) after administration of single doses of lycopene. The mean time (t(max)) to reach maximum total lycopene concentration (C(max)) ranged from 15.6 to 32.6 h. The C(max) for total lycopene ranged between 4.03 and 11.27 microg/dl (0.075-0.210 microm). Mean AUC(0-96) and elimination half-life for total lycopene ranged from 214 to 655 microg h/dl (3.986-12.201 micromol h/l) and 28.1 and 61.6 h, respectively. The changes observed in lycopene exposure parameters (e.g., C(max) and AUC(0-96)) were not proportional to increments in dose, with larger increases observed at the lowest end of the dosing range (10-30 mg). Chylomicron lycopene was measured during the first 12 h with the differences observed among the dosing groups not reaching statistical significance. These findings may reflect a process of absorption that is saturable at very low dosing levels or may be explained by the large interindividual variability in attained lycopene concentrations that were observed within each dosing group. Pharmacokinetic parameters for trans- and cis-lycopene isomers were calculated and are reported here. The formulation was well tolerated with minimal side effects, which were mainly of gastrointestinal nature and of very low grade.

Administration, Oral↗

[14C]-lycopene and [14C]-labeled polar products are differentially distributed in tissues of F344 rats prefed lycopene.

Epidemiologic evidence suggests a possible role for lycopene-rich foods in the prevention of prostate cancer and cardiovascular disease. Despite active research in disease reduction, there is a paucity of information on the absorption, biodistribution and metabolism of lycopene. The aim of this study was to evaluate the biodistribution of 14C-lycopene (specific activity, 1.83 microCi/mg) and 14C-labeled products after an oral dose of 22 microCi of 14C-lycopene in male rats that had been prefed a lycopene-containing diet (0.25 g lycopene/ kg diet) for 30 d. The percentage of 14C excreted in feces and urine over the 168 h was 68%. Quantitatively, serum 14C levels were maintained between 3 and 24 h then decreased at 72 h (P < 0.05). At all time points the majority of tissue 14C was in the liver (approximately 72%), although total hepatic 14C decreased after 24 h. In a comparison of the extrahepatic tissue at 168 h, the 14C was greatest in adipose tissue followed by spleen and then adrenal; approximately 80% of the 14C in the liver was in the cis and all-trans configuration at all time points. At 3 h, the 14C in seminal vesicles was primarily in the all-trans plus 5-cis forms (70%), but by 168 h, 55% of 14C was present as 14C-polar products. Despite the presence of unlabeled lycopene in the prostate, the primary 14C form was in 14C-polar products (67-92%), even at 3 h. The percentage and amount of 14C-polar products in the dorsolateral prostate lobe increased from 3 to 24 h and then reached a plateau. The data suggest that lycopene may be metabolized differently among tissues in rats prefed lycopene.

Adrenal Glands↗

Effects of olive oil and tomato lycopene combination on serum lycopene, lipid profile, and lipid oxidation.

OBJECTIVE: We compared the effect of two diets (a diet high in olive oil and a diet high in carbohydrate and low in olive oil) with high lycopene content and other controlled carotenoids on serum lycopene, lipids, and in vitro oxidation. METHODS: This was a randomized crossover dietary intervention study carried out in Launceston, Tasmania, Australia in healthy free-living individuals. Twenty-one healthy subjects who were 22 to 70 y old were recruited by advertisements in newspapers and a university newsletter. A randomized dietary intervention was done with two diets of 10 d each. One diet was high in olive oil and the other was high in carbohydrate and low in olive oil; the two diets contained the same basic foods and a controlled carotenoid content high in lycopene. RESULTS: Significant increases (P<0.001) in serum lycopene concentration on both diets were to similar final concentrations. Higher serum high-density lipoprotein cholesterol (P<0.01), lower ratio of total cholesterol to high-density lipoprotein (P<0.01), and lower triacylglycerols (P<0.05) occurred after the olive oil diet compared with the high-carbohydrate, low-fat diet. There was no difference in total antioxidant status and susceptibility of serum lipids to oxidation. CONCLUSIONS: Serum lycopene level changes with dietary lycopene intake irrespective of the amount of fat intake. However, a diet high in olive oil and rich in lycopene may decrease the risk of coronary heart disease by improving the serum lipid profile compared with a high-carbohydrate, low-fat, lycopene-rich diet.

Adult↗

Prevention of N-methylnitrosourea-induced colon carcinogenesis in F344 rats by lycopene and tomato juice rich in lycopene.

Epidemiological studies have suggested a protective effect of lycopene and lycopene-rich tomatoes against various cancers. Here, the inhibition of colon carcinogenesis by lycopene and tomato juice was investigated. Seven-week-old female F344/NSlc rats received an intrarectal dose of 2 mg (experiment I) or 4 mg (experiment II) of N-methylnitrosourea 3 times a week for 3 weeks, and had free access to one of 4 drinking fluids: plain water (control group), 17 ppm lycopene water solution (Ly group), and diluted tomato juice containing 17 ppm (Tj group) or 3.4 ppm (tj group) lycopene, throughout the experiments. The colon cancer incidence at week 35 was significantly lower in the Tj group, but not in the Ly group, than in the control group: 21% and 33% vs. 54%, in experiment I (24 rats in each group). It was significantly lower in the Tj group than in the tj and control groups, 40% vs. 72% and 84%, in experiment II (25 rats in each group). An appreciable amount of lycopene (0.02 microgram/g) was detected in the colon mucosa of rats in the Tj group, but not in the tj group. The results suggest that tomato juice rich in lycopene may have a protective effect against colon carcinogenesis.

Animals↗

Prostate cells exposed to lycopene in vitro liberate lycopene-enriched exosomes.

OBJECTIVES: To investigate whether cellular exosomes liberated by prostatic cell lines in culture might be acting as the transport vehicles for the dietary antioxidant lycopene, known to be sequestered in the prostate gland and to reduce the risk of developing benign prostatic hyperplasia (BPH) and prostate cancer; its subsequent secretion into seminal plasma also confers protection to spermatozoa against oxidative free-radical damage. MATERIALS AND METHODS: Using benign and malignant human prostatic cell culture models, we assessed the role that their exosomes (the putative in vitro analogues of prostasomes) might have in the transport of lycopene. RESULTS: Cells exposed to lycopene in vitro accumulated the molecule and secrete lycopene-enriched exosomes. This continued after the lycopene exposure was stopped. Extraction of lycopene from the exosomes, followed by high-performance liquid chromatography, confirmed nanogram quantities of lycopene per milligram of exosomal protein. Packaging into exosomes for export resulted in reduced degradation of this labile antioxidant, and therefore maximized the effectiveness of delivery to the sites of action. CONCLUSION: These results support the likelihood that these organelles act as the transport vehicles for this important lipophilic agent known to have a role in the chemoprevention of various urological pathologies such as BPH, prostate cancer and male infertility.

Anticarcinogenic Agents↗

Lycopene I--effect on osteoclasts: lycopene inhibits basal and parathyroid hormone-stimulated osteoclast formation and mineral resorption mediated by reactive oxygen species in rat bone marrow cultures.

Osteoclasts have been shown to produce reactive oxygen species (ROS) that can stimulate bone resorption. We explored the hypothesis that lycopene, the antioxidant carotenoid from tomatoes, can inhibit mineral resorption by inhibiting osteoclast formation and the production of ROS. Cells from bone marrow prepared from rat femur were plated into 16-well calcium phosphate-coated Osteologic Multi-test Slides and cultured in alpha-minimal essential medium supplemented with dexamethasone, beta-glycerophosphate, and ascorbic acid. The cells were treated with varying doses of lycopene in the absence or presence of parathyroid hormone (PTH) at the start of culture and at each medium change (i.e., every 48 hours). On day 8, mineral resorption pits were quantitated. Similar, parallel experiments were carried out in 12-well plastic dishes to assess tartrate-resistant acid phosphatase (TRAP) activity. Results showed that lycopene inhibited TRAP + formation of multinucleated cells in both vehicle- and PTH-treated cultures. Osteoclasts reduced nitroblue tetrazolium (NBT) to purple-colored formazan, indicating the presence of ROS in these cells. The formazan-staining cells were decreased by treatment with 10(-5) M lycopene, indicating that lycopene inhibited the formation of ROS-secreting osteoclasts. In conclusion, we have shown that lycopene inhibits basal and PTH-stimulated osteoclastic mineral resorption and formation of TRAP + multinucleated osteoclasts, as well as the ROS produced by osteoclasts. These findings are novel and may be important in the pathogenesis, treatment, and prevention of osteoporosis.

Acid Phosphatase↗