retinol-palmitate and retinyl-stearate

It is well-known that exposure to polycyclic aromatic hydrocarbons (PAH) may cause adverse health impacts. However, there are few investigations assessing the association between PAH exposure and the nutritional status of the general population. Thus, the purpose of this investigation was to assess the correlation between PAH metabolites and nutritional biomarkers in the U.S. general population. From the 2003-2006 National Health and Nutrition Examination Survey, 4,545 eligible participants were included in this cross-sectional study. To assess PAH exposure, ten urinary PAH metabolites were measured. Eleven serum nutritional biomarkers including carotenoids and vitamins were measured. The association between PAH metabolites and serum nutritional biomarkers was investigated using multivariate linear regression models. Increased 2-hydroxyfluorene was inversely correlated with elven serum nutritional biomarkers: α-carotene (β = -0.529, p < 0.001), β-cryptoxanthin (β = -0.968, p < 0.001), cis-β carotene (β = -0.149, p < 0.001), lutein and zeaxanthin (β = -1.188, p < 0.001), retinyl palmitate (β = -0.145, p < 0.001), retinyl stearate (β = -0.025, p = 0.006), total lycopene (β = -1.074, p < 0.001), trans-β carotene (β = -2.268, p < 0.001), trans-lycopene (β = -0.466, p < 0.003), retinol (β = -0.694, p = 0.004) and 25-hydroxyvitamin D (β = -1.247, p = 0.007). Increased 3-hydroxyfluorene was inversely correlated with eleven serum nutritional biomarkers: α-carotene (β = -0.740, p < 0.001), β-cryptoxanthin (β = -1.377, p < 0.001), cis-β carotene (β = -0.205, p < 0.001), lutein and zeaxanthin (β = -1.521, p < 0.001), retinyl palmitate (β = -0.209, p < 0.001), retinyl stearate (β = -0.034, p = 0.014), total lycopene (β = -1.20, p = 0.007), trans-β carotene (β = -3.185, p < 0.001), trans-lycopene (β = -0.490, p = 0.039), retinol (β = -1.366, p < 0.001) and 25-hydroxyvitamin D (β = -2.483, p < 0.001). Increased 1-hydroxypyrene was inversely correlated with eight serum nutritional biomarkers: α-carotene (β = -0.601, p = 0.001), β-cryptoxanthin (β = -1.071, p = 0.001), cis-β carotene (β = -0.170, p = 0.001), lutein and zeaxanthin (β = -1.074, p < 0.001), retinyl palmitate (β = -0.214, p = 0.005), retinyl stearate (β = -0.041, p = 0.043), total lycopene (β = -1.664, p = 0.011) and retinol (β = -1.381, p = 0.011). These results demonstrate that PAH exposure is significantly correlated with decreased levels of serum nutritional biomarkers.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Biomarkers; Carotenoids; Cross-Sectional Studies; Diterpenes; Environmental Exposure; Female; Humans; Lutein; Lycopene; Male; Middle Aged; Nutrition Surveys; Nutritional Status; Polycyclic Aromatic Hydrocarbons; Retinyl Esters; Vitamin A; Zeaxanthins

To investigate the association between dietary patterns (DP), plasma vitamins and trans fatty acids (TFAs) with the likelihood of peripheral artery disease (PAD).. National Health and Nutrition Examination Survey (NHANES) data for the years 1999-2002 were used. PAD was diagnosed by ankle brachial index assessment. Plasma concentrations of vitamins were measured using high performance liquid chromatography. Vitamin D levels were measured by radioimmunoassay. Analysis of covariance, principal components analysis (PCA) and adjusted logistic regression were applied, accounting for the survey design and sample weights.. Of the 4864 eligible participants, 2482 (51.0%) were men and 269 (5.5%) had prevalent PAD. PCA uncovered three DPs which accounted for 56.8% of the variance in dietary nutrients consumption including DP1 (fatty acids and cholesterol), DP2 (minerals, vitamins and fiber), and DP3 (polyunsaturated fatty acids [PUFA]). PAD patients had a significantly higher serum concentrations of trans 9-octadecenoic acid and trans 9, trans 12-octadienoic acid as well as lower plasma levels of vitamin D, retinol, retinyl stearate and retinyl palmitate (p < 0.001 for all comparisons). In models adjusted for age, race, diabetes, cholesterol, hypertension, smoking and energy intake, individuals in the highest quartile of the DP1 had higher odds for PAD compared with those in the lowest quartile [(odds ratio (OR): 6.43, 95% confidence interval (CI): 2.00-20.63 p < 0.001], while those in the highest quartile of DP2 and DP3 had lower odds of PAD relative to those in the lowest quartile (OR:0.28, OR:0.44, respectively; p < 0.001 for both comparisons).. We found that quality of diet, plasma vitamins and TFAs are associated with the likelihood of PAD. If confirmed in prospective studies, the possibility that dietary factors, plasma vitamins and TFAs might be valuable for preventing or delaying the clinical progression of PAD, should be investigated in intervention trials.

Topics: Adult; Aged; Ankle Brachial Index; Dietary Fats; Diterpenes; Fatty Acids, Unsaturated; Feeding Behavior; Female; Humans; Logistic Models; Male; Middle Aged; Nutrition Surveys; Odds Ratio; Oleic Acid; Peripheral Arterial Disease; Principal Component Analysis; Retinyl Esters; United States; Vitamin A; Vitamin D

Vitamin A (VA) deficiency and Tamm-Horsfall glycoprotein (THP), a protein that binds retinol and retinyl esters in canine urine, might be involved in the pathogenesis of urolithiasis in dogs. In the present study, we assessed levels of retinol, retinyl esters, retinol-binding protein (RBP) and THP in plasma and urine of dogs with a history of urolithiasis (n = 25) compared with clinically healthy controls (n = 18). Plasma retinol concentrations were higher in dogs with uroliths of struvit (P < 0.01), calcium oxalate (P < 0.05), urate (P < 0.01) and cysteine, but there were no differences in the concentrations of plasma RBP and retinyl esters. Excretion of urinary retinol and retinyl esters were tentatively, but not significantly higher in the stone-forming groups, which was accompanied by increased levels of urinary RBP (P < 0.01) and lower excretions in THP (P < 0.01). The results show that VA deficiency may be excluded as a potential cause for canine urolithiasis. However, the occurrence of RBP and a concomitant reduction of THP in urine indicates a disturbed kidney function as cause or consequence of stone formation in dogs.

Topics: Animals; Case-Control Studies; Diterpenes; Dog Diseases; Dogs; Female; Male; Mucoproteins; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Retinyl Esters; Urinary Calculi; Uromodulin; Vitamin A; Vitamin A Deficiency

Topics: Administration, Oral; Animals; Chylomicrons; Diet; Diterpenes; Dogs; Male; Mucoproteins; Retinyl Esters; Triglycerides; Uromodulin; Vitamin A

Topics: Animals; Carnivora; Diet; Diterpenes; Female; Ferrets; Kidney; Liver; Retinol-Binding Proteins; Retinyl Esters; Tissue Distribution; Vitamin A

A nonaqueous packed capillary electrochromatographic reversed-phase method for separation of retinyl esters has been developed. The retinyl esters all-trans-retinyl acetate, palmitate, heptadecanoate, stearate, oleoate, and linoleoate were separated on a 180 microm ID column packed with 5 microm C30 particles with a mobile phase consisting of 2.5 mM lithium acetate in N,N-dimethylformamide-methanol (99:1, v/v). With this mobile phase, the electroosmotic flow was 0.8 mm/s at 650 V/cm and 40 degrees C, and the separation was completed in less than 30 min on 30 cm columns. To obtain electrostable frits of the hydrophobic C30 material both the preparation of the frits and the conditioning of the column prior to electroconditioning were of importance. Selectivity changes were introduced by replacing up to 70% v/v of the N,N-dimethylformamide by acetonitrile. The increase in the amount of acetonitrile was, however, accompanied by a significant increase in analysis time. Liver extracts obtained from arctic seal were analyzed.

Topics: Animals; Chromatography, High Pressure Liquid; Diterpenes; Electric Conductivity; Electrophoresis, Capillary; Liver; Retinyl Esters; Seals, Earless; Temperature; Vitamin A

To assess the influence of age on vitamin A intestinal and liver metabolism in humans, the postprandial plasma concentrations of intestinal-originated vitamin A, i.e., retinyl esters, and liver-originated vitamin A, i.e., retinol, were compared in eight young (20-30 years old) and eight elderly (64-72 years old) healthy men. Plasma and chylomicron retinyl esters and retinol concentrations were measured for up to 24 h following the intake of a test meal that contained 23,300 RE retinyl palmitate. The chylomicron retinyl palmitate response (area under the curve) was not significantly different between the two groups, but its peak was slightly delayed (1 h) in the elderly men. The proportion of the different retinyl esters secreted in the chylomicrons was not significantly different between the two groups. The postprandial plasma retinol concentration did not change in the young participants, whereas it significantly increased in the elderly. These results suggest that vitamin A intestinal absorption and retinol intestinal esterification processes are not markedly modified in the elderly, whereas the chylomicron clearance and the regulation of postprandial plasma retinol concentration are apparently altered in these subjects.

Topics: Adult; Aged; Aging; Chylomicrons; Diterpenes; Eating; Fasting; Humans; Lipids; Male; Middle Aged; Osmolar Concentration; Retinyl Esters; Triglycerides; Vitamin A

The effects of lutein and lycopene on beta-carotene absorption and cleavage were investigated in 12 male subjects. Responses of carotenoids and retinyl palmitate in the triacylglycerol-rich lipoprotein (TRL) fraction after a separate 15-mg beta-carotene dose were compared with those after a dose of 15 mg beta-carotene combined with 15 mg lycopene or lutein (given as natural concentrates or extracts). After combined dosing with lutein, the areas under the curve (AUCs) of beta-carotene and retinyl palmitate in the TRL fraction, adjusted for the triacylglycerol response, were 66% (P = 0.019) and 74% (P < 0.059), respectively, compared with 100% after dosing with beta-carotene alone. After combined dosing with lycopene these percentages were 90% and 101%, respectively (NS). Beta-carotene conversion, estimated from the ratio between the AUC for retinyl esters and beta-carotene, assuming eccentric cleavage, was 69%, 71%, and 72% for treatment with only beta-carotene, beta-carotene combined with lycopene, and beta-carotene combined with lutein, respectively. In addition, a pilot study was performed to evaluate application of TRL response curves to measure absorption of carotenoids from vegetable sources (15 mg carotenoid as carrots, spinach, and tomato paste). As compared with the carotenoid concentrates, responses were considerably lower or hardly measurable (beta-carotene and retinyl palmitate after carrots, lutein after spinach), except for lycopene and retinyl palmitate after a single dose of tomato paste. In conclusion, this study showed that lutein, but not lycopene, negatively affected beta-carotene absorption when given simultaneously with beta-carotene but apparently had no effect on beta-carotene cleavage.

Topics: Absorption; Adult; beta Carotene; Carotenoids; Diterpenes; Humans; Kinetics; Lipoproteins; Lutein; Lycopene; Male; Retinyl Esters; Triglycerides; Vegetables; Vitamin A

Retinyl palmitate (RP) and retinyl stearate (RS) are of central importance in the visual cycle because they are the major storage molecules for retinol. In some tissues (e.g. liver) the amount of vitamin A (mostly in the form of retinyl ester) is positively correlated with both the amount of alpha-tocopherol (alpha-T) and age. Furthermore, alpha-T is a noncompetitive inhibitor of the hydrolysis of RP. We measured RP, RS, alpha-T and beta+gamma-tocopherol (beta+gamma-T) as functions of distance from the foveal center (eccentricity) in the retina-RPE-choroid (NRC) of rhesus monkeys using high-pressure liquid chromatography. It was found that the central and peripheral NRC differed with respect to these parameters. The concentration (pmoles sq mm-1) of RP was higher in the central NRC than in the peripheral NRC and was at a maximum in the region of the fovea. Furthermore, although in the peripheral NRC. RP was well correlated with age and alpha-T (similar to other tissues), in the central NRC, RP per sq mm was more clearly related to photoreceptor density. These differences imply that the central NRC controls the concentration of RP within it, while the concentration of RP in the peripheral NRC is determined by its environment (e.g. nutrients available from blood) and the age of the individual.

Topics: Age Factors; Animals; Choroid; Diterpenes; Eye; Macaca mulatta; Pigment Epithelium of Eye; Regression Analysis; Retina; Retinyl Esters; Vitamin A; Vitamin E

A rat model was used to investigate whether high oral doses of vitamin A lead to fetal malformations and to what extent retinyl esters (RES) are transferred from the mother to the fetuses. Retinol and RES concentrations in plasma behave similarly in rats and humans. When high concentrations of vitamin A are administered, plasma retinol concentrations remain relatively constant, whereas plasma RES increased in parallel with the dose. To achieve an elevation from approximately 150 to > 1525 nmol x L(-1) in the experimental group before mating, female Ibm: RORO (spf) rats were fed a maintenance diet enriched with 15.2 x 10(3) retinol equivalents (RE) x kg(-1) at the start and increased stepwise to 52.5 x 10(3) for a total of 8 mo. A parallel subgroup was maintained to measure progress in experimental rats without interference by blood taking. Rats of the control group received the basal diet analyzed to contain 4.5 x 10(3) RE x kg(-1). Before mating the mean body weights of experimental and control rats were not significantly different. All-trans, 13-cis, 4-oxo-all-trans and 5,6-epoxy-all-trans retinoic acid (RA) concentrations were determined in maternal and fetal plasma. With high vitamin A intake, 4-oxo- and 5,6-epoxy RA concentrations were significantly higher in the fetuses than in their mothers. Although these high intakes of vitamin A by the rat dams resulted in high maternal and fetal plasma concentrations of vitamin A and its metabolites, fetal malformations were not observed. This may be due to the fact that circulating RES are not teratogenic and that after crossing the placental barrier, they are stored mainly in fetal liver.

Topics: Abnormalities, Drug-Induced; Animals; Chemical Phenomena; Chemistry, Physical; Chromatography, High Pressure Liquid; Diterpenes; Esters; Female; Maternal-Fetal Exchange; Pregnancy; Rats; Retinyl Esters; Vitamin A

The adrenal cortexes of humans and rodents accumulate lipofuscin with age, but the chemical nature of the substance that produces lipofuscin fluorescence in the gland is not known. Analysis of rat adrenal nonpolar lipids revealed a fluorescence profile with increased intensity in the lipids extracted from older animals (23-24 months > 6 months > 6 weeks). The peak occurred at a wavelength of 470 +/- 5 nm(n = 26) when excited at 340 nm. After sucrose density gradient centrifugation, the fluorescent substance was primarily concentrated in subcellular lipid droplets rather than supernatant or particulate. Prolonged stimulation of rats with ACTH for 7 consecutive days caused 14-51% decreases in the fluorescence levels, with a tendency of return to control levels poststimulation regardless of age. In contrast, the nonpolar lipids of mouse adrenal tumor (Y1) cells, which contain no lipofuscin, did not display this fluorescence in the presence or absence of ACTH. The chromatographic characteristics of the substance in a silica gel-60 column resembled those of authentic retinyl palmitate and cholesteryl oleate. Analysis of the substance by HPLC demonstrated at least three prominent peaks, designated XI-3 in order. X1 and X2 were minor peaks; X3 was the major peak. Whereas none of the peaks comigrated with cholesteryl esters, X1 comigrated with authentic retinyl palmitate. Determination of the fatty acid component of the major fluorescent substance X3 by gas-liquid chromatography disclosed stearic acid. Retinyl stearate was, therefore, synthesized. The fluorescent profiles, HPLC retention time and mass spectrometric fragmentation of purified X3 substance were all identical to those of the synthetic compound. In contrast, the rat liver principally accumulated retinyl palmitate with age. Thus, we conclude that 1) the major nonpolar fluorescent substance accumulated in the rat adrenal with age is retinyl stearate, which may be a fluorophore of adrenal lipofuscin; 2) ACTH action may be related to this accumulation; and 3) the type of retinyl ester accumulated in aged animals is organ specific.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Aging; Animals; Centrifugation, Density Gradient; Cholesterol Esters; Chromatography, Gel; Chromatography, High Pressure Liquid; Diterpenes; Lipofuscin; Male; Mass Spectrometry; Rats; Rats, Inbred F344; Retinyl Esters; Spectrometry, Fluorescence; Stearic Acids; Vitamin A

Reproducibility of the relative dose response test (RDR), a test designed to measure vitamin A status, was tested in 23 Belizean children, 5-8 years after 2-week interval during which no treatment was given.. As required for the RDR test, serum retinol concentrations were determined before and 5 hours after an oral dose of vitamin A. An RDR score > 14% was used as the criterion of inadequate vitamin A status. The HPLC method used to measure serum retinol concentrations also determined the concentrations of four retinyl esters.. The RDR test was reproducible for 17 of 23 subjects: 3 scored > 14% on both tests; 14, < 14% on both. Six subjects scored > 14% on only one test. The concordance correlation coefficient (rc) for the percent change in the two tests was 0.24; for fasting serum retinol concentration, rc = 0.81. For retinyl palmitate and stearate, the esters present in highest concentrations at 5 hours, concordance correlation coefficients were 0.75 and 0.59, respectively.. The failure of the RDR test to classify 26% of the subjects reproducibly reduces the usefulness of the test. In addition, the reproducibility of the retinyl ester concentrations in serum 5 hours after the retinyl palmitate dose and the relatively high concentrations in some subjects suggests that some individuals may not metabolize sufficient retinol in 5 hours to cause a maximal increase in serum retinol, resulting in an underestimation of deficiency in a population in which the RDR test is used.

Topics: Anticarcinogenic Agents; Child; Child, Preschool; Chromatography, High Pressure Liquid; Diterpenes; Dose-Response Relationship, Drug; Female; Humans; Male; Reproducibility of Results; Retinyl Esters; Vitamin A

The kinetics of vitamin A and its major metabolites were investigated in humans. Eleven healthy male subjects ingested 105 mumol (100,000 IU) of [8,9,19-13C]retinyl palmitate in an oily solution. Twenty-seven blood samples were collected during the 1-week study. Plasma samples were analyzed for retinyl esters and for [12C]- and [8,9,19-13C]retinol. Retinol isotopes were quantified using a newly developed GC-MS method. Total retinyl esters peaked at about 4.45 mumol/L from 3.5 to 12 h after dosing. As a result of the perturbation of the tracee system, the plasma concentration of [12C]retinol increased and then decreased as the concentration of [8,9,19-13C]retinol increased, indicating rapid distribution kinetics. A broad single peak (1.16 +/- 0.32 mumol/L) was observed for [8,9,19-13C]retinol at about 10 to 24 h postdose; this likely reflects hepatic secretion of [8,9,19-13C]retinol associated with retinol-binding protein. Then, declining levels of the tracer and increasing levels of the tracee were observed. At its peak, the ingested [8,9,19-13C]retinol reached about 51% of the observed total plasma retinol concentration. This percentage dropped to 13.4% on day 7 indicating slow final elimination from plasma. Our data support the concept that the liver follows the principle "last in/first out' in maintaining vitamin A homeostasis.

Topics: Administration, Oral; Adult; Carbon Isotopes; Diterpenes; Esters; Gas Chromatography-Mass Spectrometry; Humans; Male; Retinyl Esters; Time Factors; Vitamin A

A high-performance liquid chromatographic method for the simultaneous determination of retinol and retinyl esters in human liver samples is presented. The free retinol and the prevalent retinyl esters (retinyl palmitate, oleate and stearate) are resolved within less than 30 min, using an octasilyl (C8)-substituted column and an isocratic elution with methanol-water as mobile phase. This method allows to determine in duplicate all retinyl ester concentrations in small liver samples (3-10 mg of fresh tissue). The results obtained from thirteen patients without liver disease are described.

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Diterpenes; Esters; Female; Humans; Liver; Male; Middle Aged; Reproducibility of Results; Retinyl Esters; Spectrophotometry, Ultraviolet; Vitamin A

We determined the kinds and amounts of vitamin A compounds (retinol and various retinyl esters) circulating in serum and stored in liver and other selected tissues of ferrets, using high-performance liquid chromatography.. The concentration of total retinyl esters in serum (43 +/- 1 mumol/L, mean +/- SEM) was 25 times greater than that of retinol (1.7 +/- 0.2 mumol/L). In serum, 56% of retinyl esters was retinyl stearate, 33% was retinyl palmitate, and 5% was retinyl oleate. In contrast, in liver, vitamin A was stored primarily as retinyl palmitate (51%); smaller amounts of retinyl oleate (19%) and retinyl stearate (16%) were found. In kidneys, adrenals, small intestine, adipose tissue, skin, stomach, and eyes, retinyl palmitate was also the predominant retinyl ester, followed by retinyl stearate. In colon, lungs, and bladder, equal amounts of retinyl palmitate and retinyl stearate were observed. Other retinyl esters present in smaller amounts in most of these tissues were retinyl oleate, retinyl linoleate and/or -myristate, retinyl heptadecanoate, retinyl arachidonate, and retinyl laurate.. Thus, the primary form of vitamin A that circulates in the blood of ferrets is retinyl stearate, whereas the primary storage form of the vitamin in tissues is retinyl palmitate. Concentrations of total vitamin A in ferret serum and other tissues were 3-73 times greater than those reported for their corresponding human tissues.

Topics: Animals; Diterpenes; Esters; Ferrets; Male; Organ Specificity; Retinyl Esters; Vitamin A

Topics: Animals; beta Carotene; Carotenoids; Cholesterol; Diterpenes; Ferrets; Lipoproteins; Lycopene; Male; Retinyl Esters; Stereoisomerism; Vitamin A

The concentrations of beta-carotene, retinol and retinyl esters in serum and selected tissues of ferrets fed diets supplemented with beta-carotene (80 micrograms/g wet diet) for 3 wk were determined. The initial concentration of serum beta-carotene was 0.011 +/- 0.006 mumol/L (mean +/- SEM); at the end of the experimental period it was 5.75 +/- 1.60 mumol/L. No significant differences in serum retinol and total retinyl esters were observed between beta-carotene-fed and control ferrets that had been fed an unsupplemented diet. The predominant retinyl esters in serum were retinyl stearate (53%) and retinyl palmitate (35%). Of the tissues analyzed after beta-carotene feeding, the liver contained the highest concentration of beta-carotene (78.8 +/- 18.8 nmol/g). Other tissues that contained beta-carotene in amounts ranging from 17 to 20 nmol/g were adrenals, small intestine, stomach and colon; lesser amounts (6.9 nmol/g) were found in kidneys. Amounts ranging from 1.2 to 2.3 nmol/g were found in muscle, bladder, adipose tissue, lungs and skin; only 0.37 and 0.34 nmol/g were present in brain and eyes, respectively. Thus, like humans, ferrets have the capacity to absorb intact beta-carotene and to store this compound in tissues, especially the liver. However, compared with humans, ferrets have elevated concentrations of retinyl esters in serum, liver and other tissues.

Topics: Absorption; Adrenal Glands; Animals; beta Carotene; Carotenoids; Diet; Diterpenes; Ferrets; Gastric Mucosa; Intestinal Mucosa; Liver; Male; Organ Specificity; Retinyl Esters; Vitamin A

Vitamin A (retinol) is essential for normal differentiation and integrity of developing respiratory epithelium and its deficiency has been linked to an increased susceptibility to lung injury. Because significant vitamin-A storage occurs in the fetal lung near term in the perinatal rat, prematurely born animals deprived of adequate stores in their lungs may be susceptible to the adverse effects of vitamin-A deficiency. It would be desirable if lung vitamin-A stores could be augmented with maternal administration, but the feasibility of this strategy has not been reported. We therefore conducted this study in rats to determine whether maternal administration of vitamin A could increase the lung stores of vitamin A in the offspring. Vitamin-A-sufficient pregnant rats were given a single dose of either vitamin A (50,000 IU retinyl palmitate) or 0.9% saline solution on gestational day 16 (term = 21 days) by the intragastric route. High-performance liquid chromatography was used to measure concentrations of vitamin A and its esters in fetal and neonatal lungs and livers at times ranging from gestational day 17 through 21, and from postnatal day 1 through 14. The concentrations of vitamin-A esters in the lungs of fetuses and newborn pups of the vitamin-A-treated animals were significantly (1.7- to 7.1-fold) higher than those of the control group. This increase in the lung vitamin-A ester concentrations was seen within 24 h of maternal administration and persisted throughout the 14-day postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Diterpenes; Dose-Response Relationship, Drug; Female; Fetus; Gestational Age; Liver; Lung; Maternal-Fetal Exchange; Organ Size; Perinatology; Placenta; Pregnancy; Rats; Rats, Inbred Strains; Retinyl Esters; Vitamin A

Many tissues which require vitamin A store the vitamin as long-chain fatty acyl esters of retinol. As part of a study designed to characterize vitamin A metabolism in the lacrimal gland, which transports retinol from blood to lacrimal gland fluid, extracts from lacrimal glands of rabbits and rats were analyzed by non-aqueous high performance liquid chromatography. Retinyl linoleate, retinyl palmitate, and retinyl stearate were identified in these extracts by their co-elution with standards, their retention time relative to retinyl palmitate, and their susceptibility to hydrolysis by saponification. Retinyl palmitate was present in rabbit lacrimal gland at 51.0 +/- 10.1 ng/g tissue. After treatment of vitamin A-deficient rabbits with orally administered [11,12-3H] retinyl acetate, the radiolabeled esters retinyl linoleate, palmitate, and stearate were extracted from the lacrimal glands. These data show that the lacrimal gland stores vitamin A as fatty acyl esters of retinol.

Topics: Animals; Chromatography, High Pressure Liquid; Diterpenes; Lacrimal Apparatus; Rabbits; Retinoids; Retinyl Esters; Vitamin A; Vitamin A Deficiency

Experiments were conducted to determine the influence of dietary levels of vitamin A and alpha-tocopherol on the amounts and composition of retinyl esters in the retinal pigment epithelium of light-adapted albino rats. Groups of rats were fed diets containing alpha-tocopherol and either no retinyl palmitate, adequate retinyl palmitate, or excessive retinyl palmitate. Other groups of rats received diets lacking alpha-tocopherol and containing the same three levels of retinyl palmitate. Retinoic acid was added to diets lacking retinyl palmitate. After 27 weeks, the animals were light-adapted to achieve essentially total visual pigment bleaches, and the neural retinas and retinal pigment epithelium-eyecups were then dissected from each eye for vitamin A ester determinations. Almost all of the retinyl esters were found in the retinal pigment epithelium-eyecup portions of the eyes, mainly as retinyl palmitate and retinyl stearate. Maintaining rats on a vitamin A-deficient, retinoic acid-containing diet led to significant reductions in retinal pigment epithelial retinyl ester levels in rats fed both the vitamin E-supplemented and vitamin E-deficient diets; contrary to expectations, the effect of dietary vitamin A deficiency was more pronounced in the vitamin E-supplemented rats. Vitamin A deficiency in retinoic acid-maintained animals also led to significant reductions in retinyl palmitate-to-stearate ester ratios in the retinal pigment epithelia of both vitamin E-supplemented and vitamin E-deficient rats. Excessive dietary intake of vitamin A had little, if any, effect on retinal pigment epithelial retinyl ester content or composition. Vitamin E deficiency resulted in significant increases in retinal pigment epithelial retinyl palmitate content and in palmitate-to-stearate ester ratios in rats fed all three levels of vitamin A, but had little effect on retinal pigment epithelial retinyl stearate content. In other tissues, vitamin E deficiency has been shown to lower vitamin A levels, and it is widely accepted that this effect is due to autoxidative destruction of vitamin A. The increase in retinal pigment epithelial vitamin A ester levels in response to vitamin E deficiency indicates that vitamin E does not regulate vitamin A levels in this tissue primarily by acting as an antioxidant, but rather may act as an inhibitor of vitamin A uptake and/or storage. The effect of vitamin E on pigment epithelial vitamin A levels may be mediated by the vitamin E-induced ch

Topics: Animals; Diet; Diterpenes; Male; Pigment Epithelium of Eye; Rats; Rats, Inbred F344; Retinyl Esters; Vitamin A; Vitamin E

Vitamin A plays a central role in visual transduction and in maintaining the structural integrity of the retina. It is possible that age-related alterations in vitamin A metabolism in the eye could contribute to the impairment of visual function that occurs during senescence. Therefore, investigations were conducted to determine whether the metabolism of this vitamin in the rat retina was altered during aging. Pigmented rats aged 12-, 22-, and 32 months were dark-adapted, and one eye from each animal was enucleated under dim red light. The neural retinas were separated from the retinal pigment epithelium (RPE)-choroid-scleral complexes, and the amounts and forms of vitamin A in both tissues were determined. The animals were then fully light-adapted, and the same measurements were performed on the tissues from the remaining eye of each rat. A number of age-related alterations in the vitamin A composition and content of the retina and RPE were observed. The most pronounced of these changes were significant increases in the ratios of retinyl palmitate to retinyl stearate with advancing age in both the neural retina and RPE. The total vitamin A ester contents of the RPEs increased during senescence in the dark-adapted state, but not in the light-adapted state. Retinyl ester levels in the neural retinas, on the other hand, did not differ significantly between 12- and 32-month-old animals in either the light-adapted or dark-adapted states. The amounts of all-trans retinol in the neural retinas decreased during aging, mainly in the dark-adapted state, whereas aging had no influence on RPE all-trans retinol content. The age-related alterations in metabolism of vitamin A that these observations reflect may be related to certain changes in visual function that occur during senescence.

Topics: Adaptation, Ocular; Aging; Animals; Diterpenes; Male; Pigment Epithelium of Eye; Rats; Rats, Inbred ACI; Retina; Retinyl Esters; Vitamin A

Cellular retinol-binding protein (type II) (CRBP(II)), a newly described retinol-binding protein, is present in the small intestinal absorptive cell at high levels. Retinol (vitamin A alcohol) presented as a complex with CRBP(II) was found here to be esterified by microsomal preparations from rat small intestinal mucosa. The esterification observed utilized an endogenous acyl donor(s) and produced retinyl esters containing linoleate, oleate, palmitate, and stearate in a proportion quite similar to that previously reported for retinyl esters in lymph and isolated chylomicrons of rat. No dependence on endogenous or exogenous acyl-CoA could be demonstrated. The apparent Km for retinol-CRBP(II) in the reaction with endogenous acyl donor was 2.4 X 10(-7) M. Retinol presented as a complex with CRBP(II) was esterified more than retinol presented as a complex with cellular retinol-binding protein or retinol-binding protein, two other proteins known to bind retinol in vivo, but about the same as retinol presented bound to bovine serum albumin or beta-lactoglobulin. The ability of protein-bound retinol to be esterified was related to accessibility of the hydroxyl group, as judged by the ability of alcohol dehydrogenase to oxidize the bound retinol. However, whereas retinol bound to CRBP(II) was unavailable for esterification in any acyl-CoA-dependent reaction, retinol bound to bovine serum albumin was rapidly esterified in a reaction utilizing exogenous acyl-CoA. The results suggest that one of the functions of CRBP(II) is to accept retinol after it is absorbed or generated from carotenes in the small intestine and present it to the appropriate esterifying enzyme.

Topics: Acyl Coenzyme A; Animals; Diterpenes; Intestine, Small; Isoenzymes; Kinetics; Microsomes; Protein Binding; Rats; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Retinyl Esters; Serum Albumin; Vitamin A

Retinol and retinyl esters are measured in serum or plasma samples by gradient, normal-phase, adsorption "high-performance" liquid chromatography, with ultraviolet detection at 325 nm. The four major circulating retinyl esters in humans (esters of palmitate, stearate, oleate, and linoleate) are coeluted as a single peak. Retinyl acetate is included as an internal standard, to correct for variable recovery. Retinol values so measured correlated well (r = 0.88) with those by a widely used reversed-phase chromatographic technique (Clin Chem 1983;29:708-12). The mean retinol concentration was 570 (SEM 17) micrograms/L and the mean for retinyl esters was 33 (SEM 4) micrograms/L as determined in samples from 88 fasting young adults. Concentrations of retinol in plasma as low as 50 micrograms/L can be detected in 100-microL samples, as can 10 micrograms of retinyl esters per liter. Using this method, we measured absorption of low doses of vitamin A, which may provide a more physiological approach to assessment of fat malabsorption. Additionally, the procedure proved useful for quickly screening for vitamin A toxicity. Major advantages include small sample size, direct injection of the extract ed sample without evaporation, rapid elution pattern, co-elution of major retinyl esters as a single peak, and low limit of detection.

Topics: Adult; Animals; Child; Chromatography, High Pressure Liquid; Diterpenes; Female; Humans; Hypervitaminosis A; Male; Microchemistry; Plasma; Rats; Rats, Inbred Strains; Retinyl Esters; Vitamin A

All-trans-[11-3H]retinyl acetate was injected directly into the testes of young rats and testicular and liver metabolites were analyzed by HPLC at 6, 24 and 72 h post injection. All-trans-retinyl acetate was hydrolyzed to retinol and further metabolized to polar compounds and a trace of retinoic acid, or reesterified to various retinyl esters including retinyl palmitate and retinyl stearate. Thus, retinyl ester hydrolyzing and esterifying enzymes are present in the testes of young rats. Eleven, twelve and ten radioactive peaks were observed at 6, 24 and 72 h, respectively. The amount of radioactivity in retinyl palmitate and retinyl stearate increased with time and reached 24 and 4%, respectively, by 72 h. Although retinol predominated, retinyl palmitate was the major esterified form in testis. The amount of radioactivity in retinol and retinyl acetate decreased with time and increased in unidentified metabolites and retinyl esters. An insignificant amount of radioactivity was found in liver. We conclude from these results that some vitamin A is stored/accumulated in the testes as retinyl esters in order to support the process of spermatogenesis and other physiological functions and that the retinol esterifying enzyme is quite active in the testes of young rats.

Topics: Animals; Chromatography, High Pressure Liquid; Diterpenes; Injections; Liver; Male; Rats; Rats, Inbred Strains; Retinyl Esters; Testis; Time Factors; Tretinoin; Vitamin A

Highly purified sinusoidal (fat-storing, Kupffer and endothelial cells) and parenchymal cells were isolated to assess the cellular distribution of vitamin A in liver of adult vitamin A-sufficient rats. A modified simple procedure was developed for the purification of fat-storing cells from rat liver. This was achieved by a single centrifugation step in a two-layer density Nycodenz gradient. Endothelial and Kupffer cells were obtained from the same gradient and further purified by centrifugal elutriation. Reverse-phase HPLC analysis showed that fat-storing cells contained about 300-fold the amount of retinyl esters present in parenchymal cells on a mg cell protein basis. In fat-storing cells, the same retinyl esters, viz. retinyl palmitate, retinyl stearate and retinyl oleate, were present as in whole liver. It was also observed that, within 12 h after intravenous injection of chylomicron [3H]retinyl ester, most of the radioactivity had accumulated in the fat-storing cells. It is concluded that fat-storing cells are the main storage sites for vitamin A in rat liver.

Topics: Aging; Animals; Cell Separation; Chromatography, High Pressure Liquid; Chylomicrons; Diterpenes; Female; Lipid Metabolism; Liver; Rats; Retinyl Esters; Temperature; Tissue Distribution; Vitamin A

Concurrent with a phase I trial of retinol in patients with advanced cancer, we studied the plasma kinetics of both retinol and its major metabolites, retinyl palmitate and retinyl stearate. Retinol was administered to 12 patients in daily oral doses of 60,000, 100,000, 150,000, or 200,000 units/m2. Patients remained on treatment until the development of dose-limiting toxic effects or disease progression. Retinoid plasma kinetics were studied on the first day of treatment, at Weeks 2 and 4, and every 2-3 months thereafter as long as the patient remained on therapy. A high-performance liquid chromatography assay was used to quantitate the plasma concentration of both retinol and its fatty acid esters. There was no significant change in the plasma retinol concentration up to 24 hours after a single oral dose of retinol (P greater than 0.05). However, the plasma concentration of retinyl palmitate and retinyl stearate markedly increased with a mean time to peak plasma concentration of 4.3 +/- 0.7 hours. Retinyl palmitate rapidly disappeared from the plasma with an initial phase half-life of 2.2 +/- 0.9 hours. The terminal phase half-life appeared prolonged and could not be accurately determined. Retinyl stearate was detected in the plasma of all patients with plasma concentrations paralleling and ranging from 20% to 40% those of retinyl palmitate. With prolonged retinol administration, peak plasma retinyl palmitate concentrations increased with both increasing retinol dose (P less than 0.001) and increasing duration of treatment (P = 0.001). In three patients with low pretreatment plasma retinol concentrations, daily retinol administration was associated with a rise in plasma retinol concentration. Because only one patient developed serious toxic effects and all patients had markedly increased plasma concentrations of retinyl esters, no conclusion could be made about the relationship between plasma retinyl ester concentration and retinol toxicity.

Topics: Administration, Oral; Aged; Capsules; Chromatography, High Pressure Liquid; Diterpenes; Drug Evaluation; Female; Half-Life; Humans; Kinetics; Male; Middle Aged; Neoplasms; Prospective Studies; Retinyl Esters; Vitamin A