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Serum vitamins and the subsequent risk of bladder cancer.

PURPOSE: We determined whether serum vitamins are inversely related to bladder cancer risk. MATERIALS AND METHODS: A cohort of 9,345 Japanese-American men was examined from 1971 to 1977. At examination a blood specimen was obtained and the serum was frozen. After a surveillance period of more than 20 years 111 tissue confirmed incident cases of bladder cancer were identified. Stored serum and that of 111 age matched controls were tested by high pressure liquid chromatography for certain micronutrients, including lutein, zeaxanthin, anhydrolutein, alpha-cryptoxanthin, beta-cryptoxanthin, lycopene, dihydrolycopene, alpha-carotene, beta-carotene, total carotenoids, retinol, alpha-tocopherol, beta-tocopherol, gamma-tocopherol, delta-tocopherol and total tocopherols. RESULTS: Based on quartiles of serum micronutrient levels the ORs for bladder cancer were determined using the general estimating equations approach. There were statistically significant inverse linear trends in risk for alpha-carotene (p <0.01), beta-carotene (p = 0.03), lutein plus zeaxanthin (p = 0.03), beta-cryptoxanthin (p = 0.04) and total carotenoids (p = 0.02). However, after adjustment for pack-years of cigarette smoking none of the inverse trends remained significant. CONCLUSIONS: These results suggest that cigarette smoking, which is a strong risk factor for bladder cancer, may explain the apparent protective effect of individual and total carotenoids against this common cancer.

Aged↗

The relationship between smoking habits and serum levels of 8-OHdG, oxidized LDL antibodies, Mn-SOD and carotenoids in rural Japanese residents.

This study investigated the relationship between smoking habits and serum levels of 8-OHdG, oxidized LDL antibodies (oLAB), Mn-SOD, and carotenoids. Subjects were 79 males (mean age +/- standard deviation; 62.1 +/- 10.0 years) and 79 females (60.3 +/- 10.3 y) who attended a health examination screening in the town of Hokkaido, Japan. Serum 8-OHdG, Mn-SOD, and oLAB levels were measured by ELISA and serum carotenoids levels were measured by HPLC. Smoking habits were assessed by public health nurses using a questionnaire. Serum 8-OHdG levels were significantly higher in males than in females. On the other hand, serum levels of beta-carotene, alpha-carotene, beta-cryptoxanthin, and zeaxanthin and lutein were significantly lower in males than in females. Serum beta-carotene, beta-cryptoxanthin, and zeaxanthin and lutein were significantly lower in males who were current smokers, compared to non-smokers. Serum 8-OHdG levels were also significantly higher in current smokers. Furthermore, in males, serum oLAB and beta-carotene levels were significantly and negatively correlated with the number of cigarettes smoked per day. Serum Mn-SOD levels were unrelated to smoking habits in males. In conclusion, this preliminary study suggests that cigarette smoking increases serum 8-OHdG levels and reduces serum levels of oLAB and carotenoids, such as beta-carotene, beta-cryptoxanthin, and zeaxanthin and lutein in healthy male subjects. Serum levels of 8-OHdG, oLAB, and carotenoids may be useful biomarkers of oxidative conditions affected by smoking.

8-Hydroxy-2'-Deoxyguanosine↗

[Comparison of carotenoid components between GM and non-GM papaya].

We compared the carotenoid profile in GM papaya (Sunup) line to that of a non-GM one (Sunset). First, to identify major carotenoids in papaya, large-scale extraction was carried out with methanol. HPLC analyses of the methanol extracts revealed that both papayas mainly contained 5 pigments and no apparent difference was observed in the HPLC profiles. On the basis of LC/MS data and photodiode-array spectra, beta-carotene (3), lycopene (2), beta-cryptoxanthin (1), and beta-cryptoxanthin myristoyl and lauroyl esters (4 and 5) were identified as major carotenoids. It is well known that most carotenoids are labile, so a rapid analysis with precautions to avoid decomposition was developed to quantify their contents in the original fruits. Frozen samples of the fruits were sliced and a piece (about 2 g) of fruit was cut out and lyophilized. After extraction of the piece with methanol containing an anti-oxidant, BHT, the extract was further partitioned with hexane and methanol. Finally the contents of the main carotenoids in the hexane fraction were analyzed by HPLC. The contents of total carotenoids (sum of 1-5) and beta-cryptoxanthin (1, 4 and 5) in GM papaya fruit were estimated to be 0.764 +/- 0.056 and 0.604 +/- 0.051 (mumol/g), respectively and those in non-GM fruit were 0.883 +/- 0.145 and 0.705 +/- 0.098 (mumol/g), respectively. These differences are not statistically significant.

Carica↗

Plasma xanthophyll carotenoids correlate inversely with indices of oxidative DNA damage and lipid peroxidation.

Post hoc analysis of data obtained from a study designed to modulate oxidative damage by dietary intervention revealed consistently strong inverse correlations between plasma xanthophyll carotenoids and oxidative damage indices. Thirty-seven women participated in a 14-day dietary intervention that increased mean vegetable and fruit (VF) consumption to approximately 12 servings/day. An additional 10 subjects participated in an intervention that limited VF consumption to less than four servings per day. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) in DNA isolated from peripheral lymphocytes and 8-OHdG excreted in urine were measured as indices of oxidative DNA damage. Lipid peroxidation was assessed by measuring 8-epiprostaglandin F2alpha (8-EPG) in urine. Plasma levels of selected carotenoids were also determined, with the intention of using a-carotene as a biochemical index of VF consumption. Urinary 8-OHdG and 8-EPG were measured by ELISA, and plasma carotenoids were measured by high performance liquid chromatography. Lymphocyte 8-OHdG was measured by reverse phase high performance liquid chromatography with electrochemical detection. We observed that the structurally related xanthophyll carotenoids, lutein and beta-cryptoxanthin, which occur in dissimilar botanical families, were consistently inversely associated with these oxidative indices. Statistically significant inverse correlations were observed between plasma lutein and/or beta-cryptoxanthin levels and lymphocyte 8-OHdG and urinary 8-EPG. Moreover, an inverse correlation was observed between change in plasma xanthophylls and change in lymphocyte 8-OHdG concentration that occurred during the course of the study. These data lead us to hypothesize that lutein and beta-cryptoxanthin serve as markers for the antioxidant milieu provided by plants from which they are derived. Whether these carotenoids are directly responsible for the observed antioxidant phenomena merits further investigation.

8-Hydroxy-2'-Deoxyguanosine↗

Serum carotenoids and risk of cervical intraepithelial neoplasia in Southwestern American Indian women.

The objective of this research was to evaluate the association between serum carotenoids and cervical intraepithelial neoplasia (CIN) among Southwestern American Indian women. Cases were American Indian women with biopsy-proven CIN II/III cervical lesions (n = 81) diagnosed between November 1994 and October 1997. Controls were American Indian women from the same clinics with normal cervical epithelium (n = 160). All of the subjects underwent interviews and laboratory evaluations. Interviews evaluated demographic information, sexual history, and cigarette smoking. Serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were measured by high performance liquid chromatography. Cervical human papillomavirus infection was detected using a PCR-based test. Increasing levels of alpha-carotene, beta-cryptoxanthin, and lutein/zeaxanthin were associated with decreasing risk of CIN II/III. In addition, the highest tertiles of beta-cryptoxanthin (odds ratio = 0.39, 95% confidence interval = 0.17-0.91) and lutein/zeaxanthin (odds ratio = 0.40, 95% confidence interval = 0.17-0.95) were associated with the lowest risk of CIN. In conclusion, specially targeted intervention efforts to increase consumption of fruits and vegetables may protect Southwestern American Indian women from developing CIN.

Adult↗

Carotenoid composition and vitamin A value of Brazilian loquat (Eriobotrya japonica Lindl.).

Six sample lots of loquat commercialized in Campinas, Brazil were analyzed for their carotenoid composition beta-carotene (7.8 micrograms/g), zeta-carotene (0.1 micrograms/g), neurosporene (1.1 micrograms/g), beta-cryptoxanthin (4.8 micrograms/g), 5,6-monoepoxy-beta-cryptoxanthin (0.6 micrograms/g), violaxanthin (1.6 micrograms/g), (0.8 micrograms/g) and auroxanthin (0.9 micrograms/g) were identified beta-Carotene and beta-cryptoxanthin were the principal pigments, being responsible for 44% and 27%, respectively, of the total carotenoid content (17.6 micrograms/g). Both were also the principal contributors to the vitamin A value of 175 RE/100g. The carotenoid composition of the Brazilian loquat resembles that of the Japanese loquat variety Tanaka.

Brazil↗

Serum micronutrients and upper aerodigestive tract cancer.

Numerous dietary studies have found that vegetables and fruits protect against upper aerodigestive tract cancer. To evaluate the role of beta-carotene and other specific carotenoids, a nested case-control study using prediagnostic serum was conducted among 6832 American men of Japanese ancestry examined from 1971 to 1975. During a surveillance period of 20 years, the study identified 28 esophageal, 23 laryngeal, and 16 oral-pharyngeal cancer cases in this cohort. The 69 cases were matched to 138 controls. A liquid chromatography technique, designed to optimize recovery and separation of the individual carotenoids, was used to measure serum levels of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, retinol, retinyl palmitate, and alpha-, delta-, and gamma-tocopherol. With adjustment for cigarette smoking and alcohol intake, we found that alpha-carotene, beta-carotene, beta-cryptoxanthin, total carotenoids and gamma-tocopherol levels were significantly lower in the 69 upper aerodigestive tract cancer patients than in their controls. Trends in risk by tertile of serum level were significant for these five micronutrients. These significant trends persisted in cases diagnosed 10 or more years after phlebotomy for the three individual carotenoids and total carotenoid measurements. The odds ratios for the highest tertile were 0.19 (95% confidence interval, 0.05-0.75) for alpha-carotene, 0.10 (0.02-0.46) for beta-carotene, 0.25 (0.06-1.04) for beta-cryptoxanthin, and 0.22 (0.05-0.88) for total carotenoids. When the cases were separated into esophageal, laryngeal, and oral-pharyngeal cancer, both alpha-carotene and beta-carotene were consistently and strongly associated with reduced risk at each site. The findings suggest that alpha-carotene and other carotenoids, as well as beta-carotene, may be involved in the etiology of upper aerodigestive tract cancer.

Aged↗

Reference values for retinol, tocopherol, and main carotenoids in serum of control and insulin-dependent diabetic Spanish subjects.

To establish reference ranges for use in clinical and epidemiological studies, we determined concentrations of retinol, alpha-tocopherol, beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene in 450 Spanish control subjects and 123 Spanish patients with insulin-dependent diabetes mellitus (IDDM). Results were grouped according to sex, and samples were collected throughout the year. Concentrations of retinol were significantly lower and beta-carotene and alpha-carotene were higher in women than in men, both in controls and IDDM subjects, whereas beta-cryptoxanthin concentrations were higher only in control women. Conditional logistic regression analysis showed that retinol, beta-carotene, and lycopene were the variables associated with diabetes. In comparison with other populations, our controls showed, in general, ordinary concentrations of retinol, comparatively low beta-carotene and high beta-cryptoxanthin concentrations, and a relatively high alpha-tocopherol/ cholesterol ratio.

Adolescent↗

The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acid, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity.

Lung cancer cases diagnosed during the period 1975 through 1993 and matched controls were identified in the rosters of Washington County, Maryland residents who had donated blood for a serum bank in 1974 or 1989. Plasma from participants in the 1989 project was assayed for ascorbic acid; serum or plasma was assayed for participants in either project for alpha- and beta-carotene, cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Among the total group of 258 cases and 515 controls, serum/plasma concentrations were significantly lower among cases than controls for cryptoxanthin, beta-carotene, and lutein/zeaxanthin with case-control differences of -25.5, -17.1, and -10.1%, respectively. Modest nonsignificant case-control differences in a protective direction were noted for alpha-carotene and ascorbic acid. There were only trivial differences for lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Findings are reported for males and females and for persons who had never smoked cigarettes, former smokers, and current smokers at baseline. These results and those from previous studies suggest that beta-carotene is a marker for some protective factor(s) against lung cancer; that cryptoxanthin, alpha-carotene, and ascorbic acid need to be investigated further as potentially protective factors or associates of a protective factor; and that lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity are unlikely to be associated with lung cancer risk. Until specific preventive factors are identified, the best protection against lung cancer is still the avoidance of airborne carcinogens, especially tobacco smoke; second best is the consumption of a diet rich in fruits and vegetables.

Adult↗

Hypochlorite destroys carotenoids in low density lipoproteins thus decreasing their resistance to peroxidative modification.

The effects of hypochlorite (HOCl/OCl-) on the content of carotenoids (trans-lycopene, 5-cis-lycopene, alpha- and beta-carotene) and oxycarotenoids (lutein, zeaxanthin, trans- and cis-2',3'-anhydrolutein, alpha-and beta-cryptoxanthin) in human blood low-density lipoproteins (LDL) were compared using HPLC. Hypochlorite decreased the content of all the above-mentioned pigments in LDL. However, it was more reactive towards carotenoids rather than to their oxy derivatives. The ability of carotenoids and oxycarotenoids to scavenge HOCl/OCl- decreases in the series: trans-lycopene approximately 5-lycopene > alpha-carotene > beta-carotene > zeaxanthin > alpha-cryptoxanthin > cis-2',3'-anhydrolutein > beta-cryptoxanthin > trans-2',3'-anhydrolutein > lutein. Preincubation of LDL with hypochlorite decreased their resistance to CU(2+)-induced accumulation of dienic conjugates that are produced in the course of lipid peroxidation. The data suggest that hypochlorite-induced destruction of carotenoids in LDL decreases their resistance to oxidative modification, thus promoting the development of early stages of atherosclerosis.

Arteriosclerosis↗

Selected indices of micronutrient status in adult patients with sickle cell anemia (SCA).

In 24 adults with hemoglobin SS followed at the Duke University Comprehensive Sickle Cell Center, we have studied the following nutritional parameters: reduced ascorbic acid; dehydroascorbic acid; alpha and beta carotenes; cryptoxanthin; and alpha and gamma tocopherols in whole blood, washed red blood cells, plasma, or serum. In the same population we also examined reduced glutathione (GSH) and oxidized glutathione (GSSG). Fifteen of these 24 patients also were interviewed for usual dietary intakes using a 28-day dietary history. Data obtained from patients with hemoglobin SS, sickle cell anemia (SCA) were compared to those found for seven healthy normal black adults of similar age. Plasma alpha tocopherol levels were significantly lower in SCA individuals than those of the controls (P less than 0.004). Alpha and gamma tocopherol levels in sickle RBCs were significantly higher than those from RBC suspensions of control subjects (P less than 0.007, and P less than 0.001, respectively). All serum values for carotenoids examined, specifically, beta carotene, alpha carotene, and cryptoxanthin were also markedly depressed when compared to those of healthy controls (P less than 0.001, P less than 0.002, and P less than 0.001, respectively). No other statistically significant differences were found between the two groups for any of the remaining variables, including dietary estimates. Dietary analyses suggest that dietary intakes of SCA individuals exceeded the recommended daily allowances (RDA) of all macro- and micronutrients measured, and intakes of most nutrients exceeded those of black controls interviewed. These results suggest that in individuals with SCA, several micronutrients vital to maintaining reducing capacity are present in diminished quantities in plasma/serum. These anomalies exist in SCA patients even though their intake of these micronutrients are similar to those of healthy black men and women.

Adult↗

Cancer prevention by natural carotenoids.

Various natural carotenoids were proven to have anticarcinogenic activity. Epidemiological investigations have shown that cancer risk is inversely related to the consumption of green and yellow vegetables and fruits. Since beta-carotene is present in abundance in these vegetables and fruits, it has been investigated extensively as possible cancer preventive agent. However, various carotenoids which co-exist with beta-carotene in vegetables and fruits also have anti-carcinogenic activity. And some of them, such as alpha-carotene, showed higher potency than beta-carotene to suppress experimental carcinogenesis. Thus, we have carried out more extensive studies on cancer preventive activities of natural carotenoids in foods; i.e., lutein, lycopene, zeaxanthin and beta-cryptoxanthin. Analysis of the action mechanism of these natural carotenoids is now in progress, and some interesting results have already obtained; for example, beta-cryptoxanthin was suggested to stimulate the expression of RB gene, an anti-oncogene, and p73 gene, which is known as one of the p53-related genes. Based on these results, multi-carotenoids (mixture of natural carotenoids) seems to be of interest to evaluate its usefulness for practice in human cancer prevention.

9,10-Dimethyl-1,2-benzanthracene↗

Dietary and serum carotenoids and cervical intraepithelial neoplasia.

A case-control study examined the association between cervical intra-epithelial neoplasia (CIN) and serum and dietary alpha-carotene, beta-carotene, cryptoxanthin, lutein, and lycopene. Cases (n = 102) had biopsy confirmed CIN I, II or III. Controls matched for age, ethnic origin and clinic (n = 102) had normal Pap smears. Participants completed health history and food frequency questionnaires. Fasting venous blood samples were assayed for serum carotenoids. Multivariable conditional logistic regression analyses yielded odds ratios and 95% confidence intervals (CIs) for those in quartiles 3, 2, and 1 (lowest) compared to quartile 4 (highest) of serum lycopene of 3.5 (1.1-11.5), 4.7 (1.2-17.7) and 3.8 (1.1-12.4), respectively. Similar analyses yielded adjusted odds ratios (ORaS) and 95% CIs of 4.6 (1.1-19.7), 5.8 (1.6-21.3) and 5.4 (1.3-23.3) for dietary intake of lycopene. The findings for lycopene-rich foods (tomatoes) were consistent with this result. CIN was not associated with the lutein. Findings for alpha-carotene, beta-carotene and cryptoxanthin were ambiguous. Quartile of vitamin C intake was also inversely associated with CIN with ORaS and 95% CIs of 3.7 (0.9-14.6), 4.1 (1.0-17.2), and 6.4 (1.4-30.0) for those in quartiles 3, 2, and 1 compared to quartile 4.

Adult↗

Chromatographic analysis of carotenol fatty acid esters in Physalis alkekengi and Hippophae rhamnoides.

The carotenol fatty acid esters of two potentially valuable sources of plant carotenoids, sepals of Physalis alkekengi (Chinese lantern) and fruits of Hippophae rhamnoides (sea buckthorn), were separated by column chromatography and identified by HPLC-DAD and HPLC-MS. A chemical and an enzymatic hydrolysis were employed to identify the parent carotenoids and to remove the lipid components. Zeaxanthin and beta-cryptoxanthin esters represented the main fraction in P. alkekengi sepals and an important one in H. rhamnoides fruits. Beta-Cryptoxanthin palmitate and zeaxanthin dipalmitate were identified as major compounds in both plants. In P. alkekengi, the carotenoids were mainly (> 90%) esterified with palmitic acid, and a high proportion (> 80%) of saturated medium chain fatty acids was found (by GC-MS) in the total lipid extract. Although the total lipid extract of H. rhamnoides contained significant amounts of unsaturated fatty acids, especially oleic and palmitoleic acids, the xanthophylls were mainly esterified with saturated fatty acids. The oleoresins of both species represent potential sources of carotenoid esters and can be used as food additives, cosmetic ingredients or nutraceuticals.

Chromatography, High Pressure Liquid↗

Carotenoid supply in breast-fed and formula-fed neonates.

UNLABELLED: Carotenoids have various biological functions including their role as antioxidants. For humans fruits and vegetables are the only source of carotenoids. In the first months breast milk and/or formula preparations are the only nutrition for infants. To study the influence of nutrition on the plasma carotenoid profile in newborns, breast milk, different formula preparations, and the plasma of breast-fed (BF) and formula-fed (FF) newborns were analyzed by high-performance liquid chromatography. The method used allowed beta-carotene, alpha-carotene, lycopene, and beta-cryptoxanthine to be detected and all four were found in breast milk. In colostrum carotenoids were up to five times higher than in mature breast milk (P<0.05). In contrast, not all carotenoids could be found in formula preparations. Beta-carotene was detected in four out of eight, and beta-cryptoxanthine in three out of eight formula preparations. Lycopene and alpha-carotene were not detectable in any of the formula preparations. Four formula preparations did not contain any carotenoids. FF infants had different plasma carotenoid profiles compared to BF infants. beta-carotene was significantly lower in FF infants [14 (0-32) microg/l, median and interquartile ranges] than in infants after birth [24 (19-310) microg/l, P<0.05], and BF infants [32 (22-63) microg/l, P<0.05]. While newborns after birth had measurable plasma concentrations of lycopene (16 [14-18] microg/l) and of alpha-carotene [5 (0-8) microg/l), these carotenoids were no longer detectable in FF infants after day 14. CONCLUSION: FF and BF infants show significant biochemical differences in plasma carotenoid concentrations.

Antioxidants↗

The development and application of a carotenoid database for fruits, vegetables, and selected multicomponent foods.

A carotenoid database for individual and multicomponent foods has been compiled that contains values for the five most common carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein) in 2,458 fruits, vegetables, and multicomponent foods containing fruits and vegetables. The database was used to estimate intakes of specific carotenoids for 19- to 50-year-old women (n = 1,102), using food consumption data obtained from dietary recalls in the US Department of Agriculture Continuing Survey of Food Intake by Individuals, 1986. The major contributors of alpha-carotene were carrots consumed as a single food or as an ingredient in multicomponent foods. Carrots, cantaloupe, and broccoli were the main sources of beta-carotene. Orange juices and blends, oranges, and tangerines were important contributors of beta-cryptoxanthin. Tomatoes and tomato products consumed as single foods or as ingredients in multicomponent foods provided most of the dietary lycopene. Contributors of lutein + zeaxanthin included collard, mustard, or turnip greens; spinach; and broccoli. The per capita consumption of total carotenoids (the sum of the five specific carotenoids) among these women was approximately 6 mg/day.

Adult↗

Low plasma levels of oxygenated carotenoids in patients with coronary artery disease.

BACKGROUND AND AIMS: Low circulating levels of carotenoids have been associated with cardiovascular disease. The distribution of different carotenoids in blood may have an impact on the cardioprotective capacity. The aim of the present study was to determine the plasma levels of 6 major carotenoids in patients with coronary artery disease (CAD) and relate the findings to clinical, metabolic and immune parameters. METHODS AND RESULTS: Plasma levels of oxygenated carotenoids (lutein, zeaxanthin, beta-cryptoxanthin) and hydrocarbon carotenoids (alpha-carotene, beta-carotene, lycopene) were determined in 39 patients with acute coronary syndrome, 50 patients with stable CAD and 50 controls. Serological assays for inflammatory activity and flow cytometrical analysis of lymphocyte subsets were performed. Both patient groups had significantly lower plasma levels of oxygenated carotenoids, in particular lutein+zeaxanthin, compared to controls. Low levels of oxygenated carotenoids were associated with smoking, high body mass index (BMI), low high density lipoprotein (HDL) cholesterol and, to a minor degree, inflammatory activity. Plasma levels of lutein+zeaxanthin were independently associated with the proportions of natural killer (NK) cells, but not with other lymphocytes, in blood. CONCLUSION: Among carotenoids, lutein+zeaxanthin and beta-cryptoxanthin were significantly reduced in CAD patients independent of clinical setting. The levels were correlated to a number of established cardiovascular risk factors. In addition, the relationship between NK cells and lutein+zeaxanthin may indicate a particular role for certain carotenoids in the immunological scenario of CAD.

Acute Disease↗

The effect of carotenoids on the expression of cell surface adhesion molecules and binding of monocytes to human aortic endothelial cells.

Several large epidemiological studies have shown a correlation between elevated plasma carotenoid levels and decreased risk of cardiovascular disease (CVD). One proposed mechanism for the beneficial effect of carotenoids is through functional modulation of potentially atherogenic processes associated with the vascular endothelium. To test this, we incubated confluent human aortic endothelial cell (HAEC) cultures (passages 4-8) for 24 h with each of the five most prevalent carotenoids in human plasma, which are alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and lycopene, at an approximate concentration of 1 micromol/l. Carotenoids were solubilized in 0.7% (v/v) tetrahydrofuran and incorporated into FBS before adding to cell culture medium. Due to disparate solubilities in aqueous medium, final concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and lycopene were 1.7, 1.1, 0.7, 0.9, and 0.3 micromol/l and monolayers accumulated 647, 158, 7, 113, and 9 pmol/mg protein, respectively. Monolayers were then stimulated with IL-1beta (5 ng/ml) for 6 h with subsequent determination of cell surface expression of adhesion molecules as measured by an enzyme-linked immunosorbent assay (ELISA). To assess endothelial cell adhesion to monocytes, IL-1beta-stimulated monolayers were incubated for 10 min with 51Cr-labeled U937 monocytic cells and adhesion determined by isotope counting. Pre-incubation of HAEC with beta-carotene, lutein and lycopene significantly reduced VCAM-1 expression by 29, 28, and 13%, respectively. Pre-incubation with beta-carotene and lutein significantly reduced E-selectin expression by 38 and 34%, respectively. Pre-treatment with beta-carotene, lutein and lycopene significantly reduced the expression of ICAM-1 by 11, 14, and 18%, respectively. While other carotenoids were ineffective, lycopene attenuated both IL-1beta-stimulated and spontaneous HAEC adhesion to U937 monocytic cells by 20 and 25%, respectively. Thus, among the carotenoids, lycopene appears to be most effective in reducing both HAEC adhesion to monocytes and expression of adhesion molecules on the cell surface.

Anticarcinogenic Agents↗