Biomedical subjects

Robert S Parker

Publications and source records attributed to Robert S Parker.

18 recordsLinked to original sources

PubMed2006

A mass balance and disposition study of the DNA methyltransferase inhibitor zebularine (NSC 309132) and three of its metabolites in mice.

PURPOSE: To elucidate the in vivo metabolic fate of zebularine (NSC 309132), a DNA methyltransferase inhibitor proposed for clinical evaluation in the treatment of cancer. EXPERIMENTAL DESIGN: Male, CD(2)F(1) mice were dosed i.v. with 100 mg/kg 2-[(14)C]zebularine. At specified times between 5 and 1,440 minutes, mice were euthanized. Plasma, organs, carcass, urine, and feces were collected and assayed for total radioactivity. Plasma and urine were also analyzed for zebularine and its metabolites with a previously validated high-pressure liquid chromatography assay. A similar experiment was done with 2-[(14)C]uridine, the proposed primary metabolite of zebularine. RESULTS: Maximum plasma concentrations were 462, 306, 33.6, 21.7, and 11.5 mumol/L for total radioactivity, zebularine, uridine, uracil (each at 5 minutes), and dihydrouracil (at 15 minutes), respectively. Total radioactivity, zebularine, uridine, uracil, and dihydrouracil were rapidly eliminated from plasma, and after 45 minutes, none of the individual compounds could be quantitated by high-pressure liquid chromatography. Plasma data were consistent with sequential conversion of zebularine to uridine, uracil, and dihydrouracil. 2-Pyrimidinone was not observed. Prolonged retention of radioactivity, at concentrations higher than in plasma, was observed in tissues. Recovery of given radioactivity in urine (30.3% of dose), feces (0.4% of dose), cage wash (7.9% of dose), and tissues and carcass (6.1% of dose) after 24 hours implied that up to 55% of radioactivity was expired as (14)CO(2). Comparison of zebularine and uridine pharmacokinetic data indicated that approximately 40% of the zebularine dose was converted to uridine. CONCLUSIONS: Zebularine is extensively and rapidly metabolized into endogenous compounds that are unlikely to have effects at the concentrations observed.

Animals↗

PubMed2006

Dietary flavonoids with a catechol structure increase alpha-tocopherol in rats and protect the vitamin from oxidation in vitro.

To identify dietary phenolic compounds capable of improving vitamin E status, male Sprague-Dawley rats were fed for 4 weeks either a basal diet (control) with 2 g/kg cholesterol and an adequate content of vitamin E or the basal diet fortified with quercetin (Q), (-)-epicatechin (EC), or (+)-catechin (C) at concentrations of 2 g/kg. All three catechol derivatives substantially increased concentrations of alpha-tocopherol (alpha-T) in blood plasma and liver. To study potential mechanisms underlying the observed increase of alpha-T, the capacities of the flavonoids to i) protect alpha-T from oxidation in LDL exposed to peroxyl radicals, ii) reduce alpha-tocopheroxyl radicals (alpha-T (.) ) in SDS micelles, and iii) inhibit the metabolism of tocopherols in HepG2 cells were determined. All flavonoids protected alpha-T from oxidation in human LDL ex vivo and dose-dependently reduced the concentrations of alpha-T (.) . None of the test compounds affected vitamin E metabolism in the hepatocyte cultures. In conclusion, fortification of the diet of Sprague-Dawley rats with Q, EC, or C considerably improved their vitamin E status. The underlying mechanism does not appear to involve vitamin E metabolism but may involve direct quenching of free radicals or reduction of the alpha-T (.) by the flavonoids.

Animals↗

PubMed2006

Dynamic modeling of free fatty acid, glucose, and insulin: an extended "minimal model".

BACKGROUND: The mathematical models for patients with diabetes proposed in the literature since the late 1970s are mainly glucocentric (glucose-based); hence, the contribution of free fatty acid (FFA) metabolism in the body and its glucose-insulin interactions have been largely ignored. However, approximately 90% of the muscle energy is derived from FFA metabolism when the body is at rest. Furthermore, significant interactions exist among FFA, glucose, and insulin. With the long-term goal of developing a closed-loop glucose control system, a model of the major energy-providing substrate dynamics is required. METHODS: The Bergman minimal model was extended to include plasma FFA dynamics, and its interaction with glucose and insulin dynamics, with a primary focus on patients with Type 1 diabetes. Differential equations were developed for plasma FFA concentrations and "remote" FFA effects on glucose uptake, as well as "remote" insulin effects on plasma FFA concentrations. Parameters for the model were estimated from experimental data provided in the scientific literature. RESULTS: The minimal model was extended in order to capture three major metabolic aspects: the antilipolytic effect of insulin; the lipolytic effect of prolonged hyperglycemia; and the impairing effect of FFA on glucose uptake rate. The dynamic fit of glucose, FFA, and insulin profiles is consistent with published data. CONCLUSIONS: The extended minimal model successfully captured the plasma FFA concentration behavior, the plasma insulin and glucose concentrations, and the physiological interactions that exist among these species. This more comprehensive description of energy-providing substrate dynamics may provide a novel simulation test-bed for analysis of patients with insulin dependent diabetes and controller design.

Blood Glucose↗

PubMed2005

In vivo fluorescence detection of glucose using a single-walled carbon nanotube optical sensor: design, fluorophore properties, advantages, and disadvantages.

In this work, several aspects of in vivo glucose detection using a nanotube-based optical sensor are considered. The optical properties of commonly used organic and nanoparticle fluorescent probes are compared with respect to quantum yield, human tissue penetration, and photobleaching stability. The latter two factors are shown to dominate sensor viability and require a near-infrared nanoparticle fluorophore for practical device operation. The dynamics of a model optical sensor are compared to a flux-measuring electrochemical sensor of equal area using a mathematical simulation of a healthy patient ingesting three predefined meals per day. Both sensors demonstrate an approximately linear response to blood glucose levels. It is shown that the optical sensor, which transduces glucose concentration, not flux, directly is significantly more stable to membrane biofouling.

Biosensing Techniques↗

PubMed2005

Selective accumulation of alpha-tocopherol in Drosophila is associated with cytochrome P450 tocopherol-omega-hydroxylase activity but not alpha-tocopherol transfer protein.

Humans and other mammals actively discriminate among the various forms of vitamin E to selectively retain alpha-tocopherol, but the phylogenetic breadth of this trait is unknown. We sought to determine if the fruit fly, Drosophila melanogaster, similarly discriminates and if so by what mechanism. Larvae and adult flies fed diets containing predominantly gamma- and delta-tocopherols were enriched in alpha-tocopherol. Inclusion in the diet of piperonyl butoxide (PBO), an insect cytochrome P450 inhibitor and inhibitor of tocopherol-omega-hydroxylase activity, greatly elevated tissue levels of delta-tocopherol but not alpha-tocopherol. Drosophila microsomes exhibited tocopherol-omega-hydroxylase activity in the order of delta-T > gamma-T >> alpha-T, a pattern consistent with the effect of PBO in vivo. To determine if selectivity involved alpha-tocopherol transfer protein (alpha-TTP), adult flies were fed an equimolar mixture of d3-RRR- and d6-all-racemic alpha-tocopherol. Flies exhibited a d3/d6 ratio of 1.03, demonstrating an inability to discriminate on the basis of phytyl tail stereochemistry, a hallmark of alpha-TTP activity. We conclude that Drosophila preferentially accumulates alpha-tocopherol via a mechanism involving cytochrome P450 tocopherol-omega-hydroxylase-mediated catabolism of other tocopherols, but not a mammalian-like alpha-TTP. The selective pressure favoring this trait and its remarkable conservation from insects to humans requires elucidation.

Animals↗

PubMed2005

A novel lipoprotein-mediated mechanism controlling sexual attractiveness in a colorful songbird.

Sexually selected traits like complex vocalizations or vibrant colors communicate reliable information about mate quality when they are costly to display. Although several general condition-dependent mechanisms underlying the acquisition of mating advertisements have been identified, we rarely know the precise physiological and molecular challenges that animals must meet to develop their sexual ornaments. The flashy pigment-based colors commonly displayed by birds are ideal candidates for investigating the pathways and demands of sexual-signal expression, because we know the biochemical currency with which the trait is produced. Carotenoid colors in birds, for example, are derived from pigments that are acquired from the diet and assimilated into feathers and bare parts. In previous work, we showed that variation in the sexually attractive red carotenoid-colored beak of male zebra finches (Taeniopygia guttata) was predicted not by the amount of food or pigments ingested, but by the levels of carotenoids that birds circulated in blood. Here we elucidate a novel physiological mechanism by which birds are able to accumulate high levels of carotenoids in the body and develop a colorful bill. Carotenoids are transported through the bloodstream bound to lipoproteins. We assayed a critical component of lipoprotein particles-cholesterol-and found that males with higher cholesterol levels circulated more carotenoids and displayed redder beaks. Experimental supplementation of dietary cholesterol elevated carotenoid levels in the blood and beak hue. Experimental reductions in blood cholesterol, using the human lipid-lowering agent atorvastatin, diminished blood carotenoids and faded the beak; carotenoid and cholesterol levels were restored, however, by subsequent addition of dietary cholesterol. These results suggest that the production of circulating lipoproteins critically regulates the development of a colorful sexually selected trait in zebra finches.

Animals↗

PubMed2005

Control-relevant modeling of the antitumor effects of 9-nitrocamptothecin in SCID mice bearing HT29 human colon xenografts.

The mathematical model structure selected to describe system behavior is at least partially dependent on the proposed use of the model. In this paper, a pharmacokinetic(PK)/pharmacodynamic (PD) model for use in drug delivery algorithm synthesis is developed. The antitumor agent 9-nitrocamptothecin (9NC) was administered orally to severe combined immunodeficient (SCID) mice bearing subcutaneously implanted HT29 human colon xenografts, and the effect of 9NC on those xenografts was characterized. Different PK model structures were considered in characterizing the dynamics of the drug concentration in the plasma. Akaike's Information Criterion (AIC) was used to select the model structure maximizing fit accuracy while simultaneously minimizing the number of model parameters. The resulting PK model was a set of coupled linear ordinary differential equations able to describe the nonlinear dynamic behavior (e.g. plateauing, etc.) of the drug concentrations observed in the plasma. Pharmacodynamics were modeled by characterizing tumor growth in both the untreated and drug-treated animals. The resulting PK/PD model related drug administration to effect, and this model has a structure that facilitates future control algorithm synthesis. Control algorithms in this context would directly utilize PK/PD model predictions. These predictions would be used to determine the amount and frequency of drug administration in order to reduce the tumor burden without violating clinically relevant constraints. This methodology could then be used to aid the clinician in selecting dose levels and schedules, and extension to patient tailored treatment may eventually be feasible with this approach.

Algorithms↗

PubMed2005

Long-chain carboxychromanols are the major metabolites of tocopherols and tocotrienols in A549 lung epithelial cells but not HepG2 cells.

Human lung type II cell derived A549 epithelial cancer cells and HepG2 hepatocytes constitutively express cytochrome P4504F2, a P450 we previously identified as a tocopherol-omega-hydroxylase. To determine if A549 cells would metabolize tocochromanols via the omega-hydroxylase pathway, we compared the metabolism of tocopherols (alpha-, gamma-, delta-TOH) and tocotrienols (alpha-, gamma-, delta-T3) in these 2 cell lines. Cultures were incubated with alpha-, gamma-, or delta-TOH, or the analogous T3s, and synthesis of their metabolites quantitated by GC-MS. A549 cells metabolized all tocochromanols 2-3 times more extensively than HepG2 cells (P < 0.001) except alpha-TOH, a difference not related to cell uptake of substrate but rather was reflective of greater microsomal TOH-omega-hydroxylase enzyme activity. Notably, 9'-carboxychromanols were the major metabolites of all gamma- and delta-TOHs and T3s in A549 cultures, whereas 3'- and 5'-carboxychromanols predominated in HepG2 cultures. Accumulation of 9'-carboxychromanols in A549 cultures was due to their inefficient conversion to 7'-carboxychromanols relative to HepG2 cells. Sesamin inhibited tocochromanol metabolism in both cells types, and neither cell type exhibited evidence of alternative (sesamin-insensitive) pathways of metabolism. TOH-omega-hydroxylase activity was undetectable in rat primary lung type II cells, suggesting that expression of activity was associated with transformation of normal type II cells to cancer cells. Long-chain carboxychromanol metabolites of gamma-TOH and other forms of vitamin E can be biosynthesized in A549 cultures for assessment of their biological activity, including their potential inhibition of synthesis of inflammatory mediators.

Animals↗

PubMed2004

Dose-dependent effects of dietary alpha- and gamma-tocopherols on genetic instability in mouse Mutatect tumors.

Vitamin E in foodstuffs is a mixture of tocopherols. In mouse Mutatect tumors, a model designed to detect DNA mutations, the hypoxanthine phosphoribosyltransferase (Hprt) gene mutation frequency is associated with the number of tumor-infiltrating neutrophils and both are markedly decreased in mice fed high levels of alpha-tocopherol. Dietary alpha-tocopherol is also associated with a decrease in neutrophil-associated loss of an interleukin 8 (IL-8)-expressing transgene in this tumor model. We examined Hprt gene mutation frequency (expressed as the number of 6-thioguanine-resistant colonies per 10(5) clonable tumor cells), IL-8 transgene loss, and myeloperoxidase activity (an indirect measure of neutrophil number) in tumors from Mutatect mice fed diets supplemented with various concentrations of D-alpha-tocopherol acetate and/or D-gamma-tocopherol acetate or neither tocopherol for 4 weeks. Hprt gene mutation frequency and myeloperoxidase activity were statistically significantly lower in tumor cells from mice fed alpha-tocopherol at 50 or 100 mg/kg body weight per day than in tumor cells from mice fed 0 mg/kg body weight per day alpha-tocopherol (P<.001 for each comparison). IL-8 transgene loss occurred in 28 of 28 tumors (100%; 95% confidence interval [CI] = 86% to 100%) from mice fed alpha-tocopherol at 50 mg or less/kg body weight per day and seven of 18 tumors (39%; 95% CI = 24% to 54%) from mice fed 100 mg/kg body weight per day (P<.001, Fisher's exact test, referent groups [pooled] 0, 25, and 50 mg/kg). gamma-Tocopherol had no detectable effect on any of the three endpoints. Thus, dietary alpha-tocopherol decreases two forms of genetic instability in a dose-dependent manner in this experimental tumor model.

Analysis of Variance↗

PubMed2004

The cytotoxicity of vitamin E is both vitamer- and cell-specific and involves a selectable trait.

During a study of the effect of vitamin E in activated mouse macrophages, we observed a reduction in the viability of cells treated with various forms of vitamin E. We show in this report that some tocopherols (both gamma- and delta-tocopherol) are cytotoxic to some but not all cell types. Mouse macrophages were especially sensitive (40 micromol/L), whereas human hepatocytes and bovine endothelial cells were almost completely refractory (90 micromol/L). The fully methylated tocopherol, alpha-tocopherol (alpha-Toc), was not cytotoxic in any cell type tested. The cytotoxicity observed with delta-tocopherol (delta-Toc) was associated with 2 markers of apoptosis. Vitamer-specific cytotoxicity was not due to differences in cellular uptake/accumulation because both alpha-Toc and delta-Toc accumulated equally in any cell type tested. In contrast, the cell-specific cytotoxicity was related in part to uptake/accumulation of the tocopherols. Macrophages accumulated nearly 5 times more tocopherol compared with hepatocytes cultured under similar conditions. To address the hypothesis that uptake accounted for the cell-specific sensitivity, we developed a macrophage "subtype" that was markedly resistant (>150 micromol/L) to delta-Toc. Under many different cell culture conditions (including human serum) uptake/accumulation of tocopherols was reduced in this subtype by approximately 50%. Further selection and evaluation of this phenotype, however, demonstrated no cytotoxicity even when cellular levels were elevated. Our results show that undermethylated tocopherols are cytotoxic to macrophages and that there are independent and selectable processes that determine cellular tocopherol uptake/accumulation and delta-Toc cytotoxicity.

3T3 Cells↗

PubMed2004

Cereal alkylresorcinols elevate gamma-tocopherol levels in rats and inhibit gamma-tocopherol metabolism in vitro.

Alkylresorcinols (AR) are a class of amphiphilic phenolic lipids present in high amounts in wheat and rye bran. They have been reported to be both growth retarding and innocuous when fed to rats, and to have a broad range of bioactivities in vitro, suggested to be related to their ability to bind to proteins and modify membranes. This study was designed to test the effects of AR (purified from rye bran) on growth, tocopherol levels, and cholesterol levels in rats. Rats were fed 1 of 4 different levels of AR for 4 wk: 0 (control), 1, 2, and 4 g/kg diet. AR did not affect final body, liver, or lung weights. The AR diets increased the levels of gamma-tocopherol in liver and lungs (P < 0.05). To investigate whether AR could have increased gamma-tocopherol levels via inhibition of tocopherol-omega-hydroxylase, HepG2 cells were incubated with AR and the metabolism of gamma-tocopherol measured. AR significantly inhibited the conversion of gamma-tocopherol to its water-soluble hydroxychroman metabolite in vitro, indicating that AR may increase gamma-tocopherol levels via inhibition of tocopherol metabolism in vivo. The 4 g AR/kg diet decreased liver cholesterol (P < 0.001), but did not affect plasma lipids. AR were detected in the perirenal adipose tissue samples of rats fed AR, indicating that they can accumulate in the fatty tissues of rats. High levels of dietary AR moderately affect gamma-tocopherol, possibly via inhibition of tocopherol metabolism, and decrease liver cholesterol in rats.

Animals↗

PubMed2004

Discovery, characterization, and significance of the cytochrome P450 omega-hydroxylase pathway of vitamin E catabolism.

Tocopherols are known to undergo metabolism to phytyl chain-shortened metabolites excreted in urine. We sought to characterize the pathway, including associated enzymes, involved in this biotransformation. We previously found that human hepatoblastoma (HepG2) cultures metabolized tocopherols to their corresponding short-chain carboxychromanols. Putative metabolites of gamma-tocopherol that contained intact chromanol moieties were structurally identified using HepG2 cultures and electron impact gas chromatography-mass spectrometry. A microsomal assay for synthesis of the initial omega-oxidation metabolites was developed and used to screen several recombinant human liver cytochrome P450 isozymes for omega-hydroxylase activity. Seven metabolites of gamma-tocopherol were identified in HepG2 cultures, including 13'-hydroxy-gamma-TOH and all six carboxychromanols predicted by sequential omega-oxidation truncation. Rat and human liver microsomes catalyzed synthesis of 13'-OH- and 13'-COOH-gamma-TOH, but not other metabolites, in the presence of NADPH. Inclusion of NAD favored synthesis of the 13'-COOH metabolite. Recombinant CYP4F2, but not other major human liver CYP isoforms (including CYP3A4 and 3A7), exhibited tocopherol-omega-hydroxylase activity. Liver microsomes and recombinant CYP4F2 both exhibited substrate preference for gamma-TOH over alpha-TOH, and recent studies show that tocotrienols are catabolized more extensively than the corresponding tocopherols. Comparative rates of omega-oxidation of tocochromanols in hepatocytes are inversely related to biopotency and directly related to cytotoxicity of these substances in macrophages. The liver contains a cytochrome P450-mediated pathway that preferentially catabolizes "non-alpha" tocochromanols to excretable metabolites. This metabolic pathway appears central to the optimization of tissue tocochromanol status.

Animals↗

PubMed2003

Bioreactor state estimation and control.

Advanced control methods have been effectively employed for industrial chemical processing for decades. Only recently, however, have model-based strategies been implemented for biological processes. Some notable advances include the enhancement of metabolic flux models to describe the dynamic behavior observed in biochemical reactors. The combination of more than one type of model in a hybrid form was shown to perform well for bioprocess control applications.

Algorithms↗

PubMed2003

Dietary (+)-catechin and BHT markedly increase alpha-tocopherol concentrations in rats by a tocopherol-omega-hydroxylase-independent mechanism.

The effects of dietary (+)-catechin (CAT) and BHT on plasma and tissue concentrations of alpha-tocopherol (alpha-T), gamma-tocopherol (gamma-T) and cholesterol (C) were studied in male Sprague-Dawley rats. The rats were fed the compounds during a 4-wk period at concentrations of 2 g/kg in standardized diets, low but adequate in vitamin E, with 2 g/kg cholesterol. The CAT-regimen did not affect weight gain, feed intake or organ weights. BHT did not affect feed intake but lowered the body weight and the amount of liver lipids and increased the weights of livers and lungs relative to the body weight. Rats consuming CAT had 2.5-3.5-fold increased plasma, liver and lung alpha-T concentrations, but C concentrations remained unchanged. BHT-feeding resulted in 2.4- and 1.7-fold elevation in alpha-T but approximately 50% decrease in gamma-T concentrations in blood plasma and liver, respectively. BHT also lowered total C in the liver without affecting the concentration of C in the liver lipids. To investigate whether the alpha-T-sparing action of the studied compounds was due to the inhibition of tocopherol-omega-hydroxylase, HepG2 cells were incubated with CAT or BHT in the presence of delta-tocopherol (delta-T) and the 3'- and 5'-delta-carboxychromanol metabolites in the media were analyzed by GC/MS. Neither CAT nor BHT inhibited tocopherol-omega-hydroxylase activity in hepatocyte cultures; CAT was also inactive in a rat microsomal assay. In conclusion, both dietary CAT and BHT markedly increased alpha-T concentrations in plasma and organs of Sprague-Dawley rats by a mechanism that apparently does not involve inhibition of tocopherol-omega-hydroxylase, a key enzyme in tocopherol catabolism.

Animals↗

PubMed2002

Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status.

Postabsorptive elimination of the various forms of vitamin E appears to play a key role in regulation of tissue tocopherol concentrations, but mechanisms of tocopherol metabolism have not been elucidated. Here we describe a pathway involving cytochrome P450-mediated omega-hydroxylation of the tocopherol phytyl side chain followed by stepwise removal of two- or three-carbon moieties, ultimately yielding the 3'-carboxychromanol metabolite that is excreted in urine. All key intermediates of gamma-tocopherol metabolism via this pathway were identified in hepatocyte cultures using gas chromatography-mass spectrometry. NADPH-dependent synthesis of the initial gamma- and alpha-tocopherol 13'-hydroxy and -carboxy metabolites was demonstrated in rat and human liver microsomes. Functional analysis of several recombinant human liver P450 enzymes revealed that tocopherol-omega-hydroxylase activity was associated only with CYP4F2, which also catalyzes omega-hydroxylation of leukotriene B(4) and arachidonic acid. Tocopherol-omega-hydroxylase exhibited similar binding affinities but markedly higher catalytic activities for gamma-tocopherol than alpha-tocopherol, suggesting a role for this pathway in the preferential physiological retention of alpha-tocopherol and elimination of gamma-tocopherol. Sesamin potently inhibited tocopherol-omega-hydroxylase activity exhibited by CYP4F2 and rat or human liver microsomes. Since dietary sesamin also results in elevated tocopherol levels in vivo, this pathway appears to represent a functionally significant means of regulating vitamin E status.

Animals↗

PubMed2002

Bioavailability and vitamin A value of carotenes from red palm oil assessed by an extrinsic isotope reference method.

Red palm oil (RPO) contains high concentrations of beta- and alpha-carotene, and is presumed to possess a higher vitamin A value than other foods. The objective was to determine the metabolic vitamin A and carotene values of refined red palm oil in healthy adult subjects, using a stable isotope reference method. Twelve healthy subjects were administered a small standardised meal containing 10 g RPO (2.4 mg beta-carotene and 1.8 mg alpha-carotene) in a blended juice-based drink also containing 2 mg tetradeuterated retinyl acetate (d4-RA) as a metabolic reference. At baseline and at several times after the test meal, the concentrations of carotenes and of d4- and d0-(unlabelled) retinyl esters, in the plasma chylomicron-rich (d < 1.006) fraction were determined by high high-performance liquid chromatography and gas chromatography mass spectrometry, respectively. The masses of palm oil-derived vitamin A and carotenes absorbed ('yield') were calculated assuming 80% absorption of the d4-RA reference dose. The mean yield of retinol from the RPO was 0.41 mg, ranging from 0.17 mg to 0.86 mg. The mean yields of beta- and alpha-carotene were 0.29 mg and 0.25 mg, respectively, suggesting that beta-carotene was more extensively metabolised than alpha-carotene. Subjects assimilated an average of 23% of the dose of carotenes, as the sum of retinol and unmetabolised carotenes. The vitamin A values of red palm oil obtained under these conditions, a mean of 0.17 mg retinol absorbed per mg beta-carotene consumed (beta-carotene : retinol equivalency of 5.7:1) is higher than that of all other vegetable sources we have evaluated to date.

Antioxidants↗

PubMed2002

Alpha- and beta-carotene from a commercial puree are more bioavailable to humans than from boiled-mashed carrots, as determined using an extrinsic stable isotope reference method.

The extent to which processing affects the carotene or vitamin A value of foods is poorly understood. An extrinsic reference method was used to estimate the mass of carotenes and vitamin A derived from various preparations made from the same lot of carrots. Using a repeated-measures design, nine healthy adult subjects consumed test meals of either carrot puree (commercial baby food) or boiled-mashed carrots on separate days; six of the subjects also consumed a test meal of raw-grated carrot. Test meals supplied 34.7 micromol (18.6 mg) carrot beta-carotene (beta C), plus 6 micromol deuterium-labeled retinyl acetate (d(4)-RA) in oil solution. Baseline-adjusted carotene and retinyl ester (R-ester) area-under-curve (AUC) responses in the triacylglycerol-rich lipoprotein (TRL) fraction (0-8.5 h) were determined using HPLC and gas chromatography-mass spectrometry. The masses of absorbed beta C, alpha-carotene (alpha C) and R-ester were estimated by comparing their AUC values with that of deuterium-labeled retinyl ester (d(4)-R-ester), assuming the latter represented 80% of the d(4)-RA reference dose. Absorption of beta C and alpha C was approximately twofold greater from carrot puree than from boiled-mashed carrots, whereas the retinol yield was only marginally (P = 0.11) influenced by treatment. Carotene and R-ester absorption from raw-grated carrot was intermediate to, and did not differ significantly from the cooked preparations. The vitamin A yield (puree, 0.53 mg; boiled-mashed, 0.44 mg) of cooked carrot containing 18.6 mg beta C was substantially less than that predicted by current convention and limited primarily by intestinal carotene uptake. Processing can therefore significantly improve bioavailability of carrot carotenes, and in some cases influence the carotene value more than the intrinsic vitamin A value.

Adult↗

PubMedDate not supplied

Differential accumulation and pigmenting ability of dietary carotenoids in colorful finches.

Many animals develop bright red, orange, or yellow carotenoid pigmentation that they use to attract mates. Colorful carotenoid pigments are acquired from the diet and are either directly incorporated as integumentary colorants or metabolized into other forms before deposition. Because animals often obtain several different carotenoids from plant and animal food sources, it is possible that these pigments are accumulated at different levels in the body and may play unique roles in shaping the ultimate color expression of individuals. We studied patterns of carotenoid accumulation and integumentary pigmentation in two colorful finch species--the American goldfinch (Carduelis tristis) and the zebra finch (Taeniopygia guttata). Both species acquire two main hydroxycarotenoids, lutein and zeaxanthin, from their seed diet but transform these into a series of metabolites that are used as colorful pigments in the plumage (goldfinches only) and beak (both species). We conducted a series of carotenoid-supplementation experiments to investigate the relative extent to which lutein and zeaxanthin are accumulated in blood and increase carotenoid coloration in feathers and bare parts. First, we supplemented the diets of both species with either lutein or zeaxanthin and measured plasma pigment status, feather carotenoid concentration (goldfinches only), and integumentary color. Zeaxanthin-supplemented males grew more colorful feathers and beaks than lutein-supplemented males, and in goldfinches incorporated a different ratio of carotenoids in feathers (favoring the accumulation of canary xanthophyll B). We also fed goldfinches different concentrations of a standard lutein-zeaxanthin mix and found that at physiologically normal and high concentrations, birds circulated proportionally more zeaxanthin over lutein than occurred in the diet. Collectively, these results demonstrate that zeaxanthin is preferentially accumulated in the body and serves as a more potent substrate for pigmentation than lutein in these finches.

Alabama↗