Oxidative stress and antioxidant status in older adults with early cataract.

PURPOSE: Oxidative stress and antioxidant status were determined in forty healthy men and postmenopausal women aged 50-70 years (F25, M15), who underwent concurrent eye examinations. METHODS: Blood samples were collected for analysing major well-known antioxidants by HPLC systems with UV and ECD detectors, total antioxidant performance using a fluorometry, lipid peroxidation determined by malondialdehyde using a HPLC system with a fluorescent detector and by total hydroxyoctadecadienoic acid (HODE) and F2-isoprotanes (8-iso-PGF(2alpha)) using GC-MS. RESULTS: Twenty-seven (F17, M10) of the 40 subjects were diagnosed to have early cataracts at the onset of the study, which were regarded as age appropriate lens opacities. There was no significant difference in plasma major antioxidants, total antioxidant performance, and lipid peroxidation determined by malondialdehyde as well as 8-iso-PGF(2alpha) between the groups with and without early cataract. However, isomers of 9- and 13-(Z,E)-HODE levels were significantly higher in subjects with early cataract as compared with those of non-cataract subjects (P<0.05). CONCLUSION: Our data suggest that subjects with early cataract are under increased systemic oxidative stress, which can be identified by a sensitive biomarker of lipid peroxidation, such as isomers of HODE.

Tracing developing pathways in the brain: a comparison of carbocyanine dyes and cholera toxin b subunit.

The present study examined the efficiency of fluorescent carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylinodocarbocyanine perchlorate and cholera toxin B subunit in tracing the crossed tectal projection to the nucleus rotundus of the thalamus (tectorotundal pathways) of paraformaldehyde-fixed and living chick embryos. The tracers were injected into the optic tectum under three experimental conditions (carbocyanine postfix, carbocyanine in vivo, and cholera toxin B subunit in vivo) and the anterograde transport of the nucleus rotundus was monitored and compared. In the carbocyanine postfix method, small crystals of carbocyanine dye were inserted into the tectum of paraformaldehyde-fixed embryos. A 6-month post-insertion period was required to label the crossed tectorotundal pathway. Results showed that tectal neurons did not begin to innervate the ipsilateral nucleus rotundus until embryonic day 9 and the contralateral nucleus rotundus until embryonic day 17. This slow progression of labeling through the crossed tectal projection resulted in significant contrast of the labeling between the ipsilateral and contralateral nuclei rotundus. In the carbocyanine in vivo method, a small volume of carbocyanine dye solution was injected into the tectum of living embryos. A 8- to 12-h survival period was sufficient enough to label the tectorotundal pathway. By embryonic day 8, the labeled axons terminated in the ipsilateral nucleus rotundus and the crossed tectorotundal projection was first detected by embryonic day 10. Similarly, in the cholera toxin B subunit in vivo method, a small volume of cholera toxin B subunit solution was injected into the tectum of living embryos. After a 6- to 10-h survival period, heavily labeled axons were found to innervate bilaterally the nucleus rotundus by embryonic day 8. This appeared to be the earliest schedule for detecting the crossed tectorotundal projection, compared with that of both the postfix and in vivo methods of carbocyanine dye. Based on the differences in the detectability of the crossed tectorotundal projection between the postfix and in vivo methods, the present data suggest that the former method is of limited purpose for labeling tectal collaterals during embryogenesis. Moreover, given the rapid transport rate and absence of photobleaching, which is often seen when using carbocyanine dye, the cholera toxin B subunit in vivo method appears to be the tracer of choice for investigating embryonic pathways.

A method to measure the oxidizability of both the aqueous and lipid compartments of plasma.

The lipophilic radical initiator (MeO-AMVN) and the fluorescent probe C11BODIPY581/591 (BODIPY) were used to measure the lipid compartment oxidizability of human plasma. Aqueous plasma oxidizability was initiated by the aqueous peroxyl radical generator, AAPH, and 2',7'-dichlorodihydrofluorescein (DCFH) was employed as the marker of the oxidative reaction. The distribution in aqueous and lipid compartments of the two radical initiators was determined by measuring the rate of consumption of the plasma hydrophilic and lipophilic endogenous antioxidants. In the presence of AAPH (20 mM), the order of consumption was: ascorbic acid > alpha-tocopherol > uric acid > beta-carotene, indicating a gradient of peroxyl radicals from the aqueous to the lipid phase. When MeO-AMVN was used (2mM), beta-carotene was consumed earlier than uric acid and almost at the same time as alpha-tocopherol, reflecting the diffusion and activation of MeO-AMVN in the lipophilic phase. The rate of BODIPY oxidation (increase in green fluorescence) significantly increased after the depletion of endogenous alpha-tocopherol and beta-carotene, whereas it was delayed for 180 min when AAPH was used instead of MeO-AMVN. The measurement of lipid oxidation in plasma was validated by adding to plasma the two lipophilic antioxidants, alpha-tocopherol and beta-carotene, whose inhibitory effects on BODIPY oxidation were dependent on the duration of the preincubation period and hence to their lipid diffusion. DCFH oxidation induced by AAPH only began after uric acid, the main hydrophilic plasma antioxidant, was consumed. In contrast, when MeO-AMVN was used, DCFH oxidation was delayed for 120 min, indicating its localization in the aqueous domain. In summary, the selective fluorescence method reported here is capable of distinguishing the lipophilic and hydrophilic components of the total antioxidant capacity of plasma.

Age and bioavailability of alcohol.

UNLABELLED: It has been shown that advanced age results in a decreased first pass metabolism (FPM) of ethanol with elevated serum ethanol concentrations (SECs). It is still unknown if this is due to age by itself or to other factors like for example atrophic gastritis with decreased activity of alcohol dehydrogenase (ADH). To study the effect of age on SECs and on bioavailability of ethanol, 15 volunteers with a mean age of 71 +/- 1 year (8males and 7 females) and 16 volunteers with a mean age of 37 +/- 2 years (8males and 8 females) showing normal gastric histology received ethanol (0.225 g/kg b. w.) intravenously (iv.) and orally. RESULTS: The difference between the SEC time curves after iv. and oral ethanol administration (so called FPM of ethanol) was significantly increased in elderly subjects (54 +/- 6 vs. 12 +/- 9 %, p < 0.001). The SEC time curves after iv. ethanol application were significantly increased in the elderly (p < 0.001), whereas SECs following oral alcohol administration were significantly lower in elderly as compared to younger individuals (p < 0.02). Peak SECs following iv. application was also significantly elevated with age (52 +/- 4 vs. 31 +/- 1 mg/100 ml, p < 0.001) and occurrence of peak SECs following oral ethanol intake was significantly delayed (47 +/- 4 vs. 28 +/- 4 min, p < 0.001). No gender effect at all was observed. CONCLUSION: FPM of ethanol is inexpectedly increased in elderly with normal gastric morphology compared to young people. The elevation of SECs after iv. ethanol administration in the elderly could be explained by the reduction of the water distribution space with age, whereas the increased FPM of ethanol in elderly subjects with normal gastric morphology is probably due to a deceleration of the speed of gastric emptying leading to an increased contact time of alcohol with gastric alcohol dehydrogenase (ADH). Our data do not confirm results from other research groups showing increased SECs in the elderly after alcohol consumption. Increased SECs are therefore not due to age by itself, but are probably caused by other factors as for example atrophic gastritis which is frequently found in the elderly people and which decreases FPM of ethanol.

Restoration of retinoic acid concentration suppresses ethanol-enhanced c-Jun expression and hepatocyte proliferation in rat liver.

Chronic and excessive ethanol intake decreases hepatic retinoic acid (RA) concentrations, which may play a critical role in ethanol-induced hyperproliferation in hepatocytes. The present study was conducted to determine whether RA supplementation in chronic ethanol-fed rats could restore hepatic RA concentrations to normal levels and modulate hepatocyte hyperproliferation. Male Sprague-Dawley rats were divided into four groups: control, ethanol-fed, ethanol-fed + 50 microg all-trans-RA/kg body wt and ethanol-fed + 100 microg all-trans-RA/kg body wt. Ethanol was given to rats at 6.2% (v/v) in a liquid diet to provide 36% of total caloric intake. Control animals received the same amount of liquid diet with isocaloric maltodextrin in place of ethanol. Results show that the ethanol treatment in rats for a month significantly increased the mean number of proliferating cell nuclear antigen (PCNA)-positive hepatocytes [4.96 +/- 1.36% (ethanol-fed) versus 0.29 +/- 0.08% (control), P < 0.05]. This increase was associated with the induction of hepatic c-Jun protein (6.5-fold increase) and cyclin D1 protein (3-fold increase) in ethanol-fed animals as compared with controls. Furthermore, activator protein 1 (AP-1) DNA-binding activity was significantly higher in hepatic nuclear extracts from ethanol-fed rats than those from controls. In contrast, RA supplementation in ethanol-fed rats raised hepatic RA concentration to normal levels and almost completely abolished the ethanol-enhanced c-Jun, cyclin D and AP-1 DNA-binding activities. Moreover, RA supplementation at both doses markedly suppressed the ethanol-induced PCNA-positive hepatocytes by approximately 80%. These results demonstrate that the restoration of hepatic RA concentrations by dietary RA supplementation suppresses ethanol-induced hepatocyte proliferation via inhibiting c-Jun overexpression, and suggest that RA may play a role in preventing or reversing certain types of ethanol-induced liver injury.

In vitro inhibition of proliferation of estrogen-dependent and estrogen-independent human breast cancer cells treated with carotenoids or retinoids.

Both estrogen-receptor (ER) positive MCF-7 and ER-negative Hs578T and MDA-MB-231 human breast cancer cells were treated with carotenoids (beta-carotene, canthaxanthin and lycopene) and retinoids (all-trans-, 9-cis- and 13-cis-retinoic acid and all-trans-retinol). Among carotenoids, beta-carotene significantly reduced the growth of MCF-7 and Hs578T cells, and lycopene inhibited the growth of MCF-7 and MDA-MB-231 cells. Canthaxanthin did not affect the proliferation of any of the three cell lines. All-trans- and 9-cis-retinoic acid significantly reduced the growth of both MCF-7 and Hs578T cells, whereas 13-cis-retinoic acid and all-trans-retinol had a significant effect only on MCF-7 cells. MCF-7 and Hs578T cells treated with all-trans-retinoic acid (all-t-RA) were further studied for the mechanism behind growth inhibition. Retinoic acid receptors alpha and gamma (RARalpha, gamma) in MCF-7 cells and RARalpha, beta and gamma in Hs578T cells were not induced by all-t-RA treatment at either the protein or mRNA level. Hs578T cells treated with all-t-RA had significantly more cells in the G0/G1 stage of the cell cycle, but the same was not observed for MCF-7 cells. All-t-RA induced a dose-dependent cell death in MCF-7 cells, which may be a necrotic phenomenon. These results demonstrate that ER status is an important, although not essential factor for breast cancer cell response to carotenoid and retinoid treatments, and the mode of action of all-t-RA in MCF-7 and Hs578T cells is not through the induction of RAR. Other mechanistic pathways that are either followed by or concomitant with growth inhibition are possible.

Serum retinyl esters are not associated with biochemical markers of liver dysfunction in adult participants in the third National Health and Nutrition Examination Survey (NHANES III), 1988--1994.

BACKGROUND: Serum retinyl ester concentrations are elevated in hypervitaminosis A. It was suggested that retinyl esters >10% of total serum vitamin A indicate potential hypervitaminosis, but this cutoff was derived from small clinical samples that may not be representative of the general population. OBJECTIVE: We sought to examine the distribution of serum retinyl ester concentrations and associations between retinyl ester concentrations and biochemical markers of liver dysfunction in a nationally representative sample. DESIGN: We assessed the associations between serum retinyl ester concentrations and 5 biochemical indexes of liver dysfunction by using multivariate linear and multiple logistic regression techniques and controlling for age, sex, use of supplements containing vitamin A, alcohol consumption, smoking status, and use of exogenous estrogens in 6547 adults aged > or =18 y in the third National Health and Nutrition Examination Survey (NHANES III), 1988--1994. RESULTS: Thirty-seven percent of the sample had serum retinyl ester concentrations >10% of total serum vitamin A and 10% of the sample had serum retinyl esters >15% of total vitamin A. We found no associations between serum retinyl ester concentrations and 1) concentrations of any biochemical variable (multiple linear regression) or 2) risk of having biochemical variables above the reference range (multiple logistic regression). We did not find a serum retinyl ester value with statistically significant sensitivity and specificity for predicting increases in biochemical indexes of liver dysfunction. CONCLUSIONS: The prevalence of serum retinyl ester concentrations >10% of the total vitamin A concentration in the NHANES III sample was substantially higher than expected but elevated retinyl ester concentrations were not associated with abnormal liver function.

Effect of age on the gastrointestinal-associated mucosal immune response of humans.

Age-related changes in gastrointestinal-associated mucosal immune response have not been well studied. Thus, we investigated the effect of age on this response and compared these responses to those of peripheral immune cells. Saliva, blood, and intestinal biopsies were collected from young and old healthy subjects to determine immunoglobulin (Ig) levels and to isolate peripheral blood mononuclear cells, intraepithelial lymphocytes (IELs), and lamina propria lymphocytes (LPLs). Although subject age did not influence the level of total IgA found in saliva, IgA levels in serum increased (p <.05) with age. Older subjects' peripheral blood mononuclear cell proliferation and IL-2 production were significantly lower than those of young subjects. LPLs from older subjects produced significantly less IL-2 in response to all stimuli than did that from the young. IEL's ability to proliferate and produce IL-2 was not affected by subject age. Thus, LPL but not IEL demonstrated an age-related decline in immune function similar to that seen in peripheral lymphocytes.

Factors in aging that effect the bioavailability of nutrients.

Until a few years ago, little was known about bioavailability of micronutrients in elderly humans. It was assumed by many basic investigators and geriatricians that malabsorption of both macronutrients and micronutrients was a common problem among elderly persons. We now know that this is not the case; elderly persons who malabsorb macronutrients do so because of disease, not because of age. This report will be divided into three sections. The first section focuses on the general principles of absorptive processes in elderly persons. The second section focuses on the bioavailability of specific micronutrients in elderly persons, with specific examples of "problem" nutrients. The third section lays out a proposed research agenda for studying the bioavailability of nutrients and other active components of dietary supplements in elderly persons.

Ethanol enhances retinoic acid metabolism into polar metabolites in rat liver via induction of cytochrome P4502E1.

BACKGROUND & AIMS: Long-term and excessive ethanol intake results in decreased plasma and hepatic levels of retinoic acid (RA), the most active derivative of vitamin A. The decrease of RA by ethanol treatment has been proposed to be a cytochrome P450 enzyme (CYP)-dependent process. However, the role of the major ethanol-induced CYP, CYP2E1, in the metabolism of RA has not been defined. METHODS: In vitro incubations of RA with microsomal fractions of liver tissue containing CYPs from either ethanol-exposed or non-ethanol-exposed rats were carried out using chemical inhibitors and antibodies against various CYPs. In vivo, both ethanol-exposed and non-ethanol-exposed rats were treated with or without chlormethiazole, a specific CYP2E1 inhibitor, for 1 month. RA and its catabolic metabolites were analyzed by high-performance liquid chromatography and spectral analysis. RESULTS: Incubation of RA with the liver microsomal fraction from ethanol-exposed rats resulted in greater disappearance of RA and increased appearance of 18-hydroxy-RA and 4-oxo-RA compared with control rat liver microsomal fractions. The enhancement of RA catabolism by ethanol was inhibited by both CYP2E1 antibody and specific inhibitors (allyl sulfide and chlormethiazole) in a dose-dependent fashion, whereas the metabolism of RA into polar metabolites was abolished completely by nonspecific CYP inhibitors (disulfiram and liarozole). Furthermore, treatment with chlormethiazole in ethanol-fed rats in vivo restored both hepatic and plasma RA concentrations to normal levels. CONCLUSIONS: Ethanol-induced CYP2E1 plays a major role in the degradation of RA, which may provide a possible biochemical mechanism for chronic and excessive ethanol intake as a risk for both hepatic and extrahepatic cell proliferation and carcinogenesis.

Older men and women efficiently absorb vitamin B-12 from milk and fortified bread.

Nothing is directly known about the bioavailability of vitamin B-12 from dairy products or fortified grain products. We directly studied vitamin B-12 absorption from water, milk and fortified bread in adult subjects using (58)Co-labeled vitamin B-12 and a whole body gamma-ray counter/spectrophotometer. Sixteen healthy men and women over the age of 60 y with normal serum levels of vitamin B-12 and normal basal gastric acid secretion were studied. (58)Co vitamin B-12 (0.25 microg) was administered in water, milk or fortified bread to each subject along with 185 kBq (5.0 microCi) (51)Cr as a stool marker. Whole body counting was performed 30 min after ingestion of the radioactive dose and at 7 and 14 d after dosing. Mean absorptions from water, milk and fortified bread were 55, 65 and 55%, respectively, and did not differ. The high body retention of the extrinsic vitamin B-12 label from milk and bread may warrant a greater use of such fortified products in the elderly to ensure vitamin B-12 adequacy.

The effect of alpha-tocopherol on the oxidative cleavage of beta-carotene.

Two cleavage pathways of beta-carotene have been proposed, one by central cleavage and the other by random (excentric) cleavage. The central cleavage pathway involves the metabolism of beta-carotene at the central double bond (15, 15') to produce retinal by beta-carotene 15, 15'-dioxygenase (E.C.888990988). The random cleavage of beta-carotene produces beta-apo-carotenoids, but the mechanism is not clear. To understand the various mechanisms of beta-carotene cleavage, beta-carotene was incubated with the intestinal postmitochondrial fractions of 10-week-old male rats for 1 h, and cleavage products of beta-carotene were analyzed using reverse-phase, high-performance liquid chromatography (HPLC). We also studied the effects of alpha-tocopherol and NAD(+)/NADH on beta-carotene cleavage. In addition to beta-carotene, we used retinal and beta-apo-14'-carotenoic acid as substrates in these incubations. Beta-apo-14'-carotenoic acid is the two-carbon longer homologue of retinoic acid. In the presence of alpha-tocopherol, beta-carotene was converted exclusively to retinal, whereas in the absence of alpha-tocopherol, both retinal and beta-apo-carotenoids were formed. Retinoic acid was produced from both retinal and beta-apo-14'-carotenoic acid incubations only in the presence of NAD(+). Our data suggest that in the presence of an antioxidant such as alpha-tocopherol, beta-carotene is converted exclusively to retinal by central cleavage. In the absence of an antioxidant, beta-carotene is cleaved randomly by enzyme-related radicals to produce beta-apo-carotenoids, and these beta-apo-carotenoids can be oxidized further to retinoic acid via retinal.

Bioconversion of plant carotenoids to vitamin A in Filipino school-aged children varies inversely with vitamin A status.

BACKGROUND: It is important to understand the factors affecting strategies to improve the vitamin A status of populations. We reported previously that a 3-d deuterated-retinol-dilution (DRD) procedure might be used to indicate total body stores of vitamin A. OBJECTIVE: We studied the ability of 3-d DRD to detect changes in the body pool size of vitamin A and the effect of vitamin A status on the bioconversion of plant carotenoids to vitamin A. DESIGN: Two separate, unrelated studies were conducted in 7-13-y-old children with poor or marginal serum retinol concentrations (0.32-0.93 micromol/L) by feeding them controlled diets daily for 5 d/wk for 12 wk, after treatment with an anthelmintic drug. In school 1 (n = 27), lunch and 2 snacks that were provided at school contained 2258 retinol equivalents/d (mostly from orange fruit and vegetables) and 5.3 MJ/d from 33 g fat, 37 g protein, and 209 g carbohydrates; in school 2 (n = 25), 2 snacks provided 2.5 MJ/d from 9.4 g fat, 9.6 g protein, and 119 g carbohydrates, but no carotenes. RESULTS: In school 1, mean serum beta-carotene increased from 0.12 to 0.62 micromol/L (P = 0.0001) and serum retinol increased from 0.68 to 1. 06 micromol/L (P = 0.0001). In school 2, serum beta-carotene increased from 0.06 to 0.11 micromol/L (P = 0.0001) and serum retinol increased from 0.66 to 0.86 micromol/L (P = 0.0001). In school 1, but not school 2, improvement in serum retinol varied inversely with baseline retinol (r = -0.38, P = 0.048). In both schools, 3-d DRD showed reductions in the ratio of serum deuterated to nondeuterated retinol (D:H retinol) postintervention, denoting improvements in vitamin A status; the higher D:H retinol (ie, the poorer the status) at baseline, the greater the reduction in D:H retinol postintervention (school 1: r = -0.99, P = 0.0001; school 2: r = -0.89, P = 0.0001). CONCLUSIONS: Three-day DRD can detect changes in the body pool size of vitamin A, although a predictive equation to quantitate total body stores of vitamin A with the use of 3-d data needs to be developed. Bioconversion of plant carotenoids to vitamin A varies inversely with vitamin A status; improvement in status after dietary interventions is strongly influenced by total body stores of vitamin A and is influenced little or not at all by serum retinol.

The aging process as a modifier of metabolism.

Because elderly adults have distinct metabolic characteristics that alter various nutrient requirements, simple extrapolations of nutrient requirements for younger adults are not warranted. Gastrointestinal function is well preserved with aging regarding the digestion and absorption of macronutrients, but the aging gastrointestinal tract becomes less efficient in absorbing vitamin B-12, vitamin D, and calcium. The new dietary reference intakes considered recent studies in aging adults and concluded that the recommended dietary allowances (RDAs) should be 1200 mg and 15 microg for calcium and vitamin D, respectively, for persons over the age of 70 y. The new RDAs for riboflavin, niacin, thiamine, folate, vitamin B-6, and vitamin B-12 are not different for persons in the oldest age category (>70 y) than for those aged 51-70 y. Because this is a quickly advancing field, it will be important to closely follow new research on nutrient requirements and aging over the next several years.

Retinoids, carotenoids, and human breast cancer cell cultures: a review of differential effects.

Cancer of the breast is the most common incident cancer and cause of death from cancer in women. Several epidemiologic studies have reported a significant inverse relationship between the intake of vitamin A and/or provitamin A-rich foods and the incidence of certain cancers, including breast cancer. A large number of studies have been conducted to determine the effect of retinoids (all-trans-retinoic acid, in particular), and to a lesser extent of carotenoids, on breast cancer using cell culture models. In general, the results of these studies demonstrate beneficial effects of all-trans-retinoic acid on different breast cancer cells. This review compares studies conducted in different laboratories using retinoids and carotenoids as treatments for breast cancer cells and suggests what may be the underlying reasons for the differential effects of these compounds on the same cell lines.

Vitamin A equivalence of beta-carotene in a woman as determined by a stable isotope reference method.

BACKGROUND: Quantitative information on conversion of beta-carotene to vitamin A in humans is limited. AIM OF THE STUDY: Our laboratory has developed a stable isotope method for studying the conversion of beta-carotene (beta-C) to vitamin A. METHODS: Two dosage levels (a pharmacological dose, 126.0 mg beta-C-d8, and a physiological dose, 6.0 mg beta-C-d8) were used 2.5 y apart in an adult female volunteer to study dose effects on the conversion of beta-C to vitamin A. Blood samples were collected over 21 d. beta-C and retinol were extracted from serum and isolated by high performance liquid chromatography. The retinol fraction was derivatized to a trimethylsilyl ether which was analyzed by gas chromatograph/mass spectrometry with electron capture negative chemical ionization. RESULTS: The retinol-d4 response in the circulation peaked at 24 hours after the beta-C-d8 dose, with a higher percent enrichment after the pharmacological dose than after the physiological dose. By using retinyl acetate-d8 as the vitamin A reference, the retinol-d4 formed from 6 mg of beta-C-d8 (11.2 mumol) was calculated to be equivalent to 1.6 mg of retinol (i.e., 3.8 mg of beta-C was equivalent to 1 mg of retinol). However, the retinol-d4 formed from 126 mg of beta-C-d8 (235 mumol) was equivalent to 2.3 mg of retinol (i.e., 55 mg beta-C was equivalent to 1 mg retinol). CONCLUSION: These results provide evidence that it is feasible to use stable isotope reference method to study retinol equivalence of beta-C and that there may be a dose-dependence on bioconversion of beta-carotene to retinol.

Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density.

BACKGROUND: Lutein and zeaxanthin are the only carotenoids in the macular region of the retina (referred to as macular pigment [MP]). Foods that are rich in lutein and zeaxanthin can increase MP density. Response to dietary lutein and zeaxanthin in other tissues has not been studied. OBJECTIVE: The objective of this study was to examine tissue responses to dietary lutein and zeaxanthin and relations among tissues in lutein and zeaxanthin concentrations. DESIGN: Seven subjects consumed spinach and corn, which contain lutein and zeaxanthin, with their daily diets for 15 wk. At 0, 4, 8, and 15 wk and 2 mo after the study, serum, buccal mucosa cells, and adipose tissue were analyzed for carotenoids, and MP density was measured. RESULTS: Serum and buccal cell concentrations of lutein increased significantly from baseline during dietary modification. Serum zeaxanthin concentrations were greater than at baseline only at 4 wk, whereas buccal cell and adipose tissue concentrations of zeaxanthin did not change. Adipose tissue lutein concentrations peaked at 8 wk. Changes in adipose tissue lutein concentration were inversely related to the changes in MP density, suggesting an interaction between adipose tissue and retina in lutein metabolism. To investigate the possibility of tissue interactions, we examined cross-sectional relations among serum, tissue, and dietary lutein concentrations, anthropometric measures, and MP density in healthy adults. Significant negative correlations were found between adipose tissue lutein concentrations and MP for women, but a significant positive relation was found for men. CONCLUSION: Sex differences in lutein metabolism may be an important factor in tissue interactions and in determining MP density.

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.