retinol-acetate and retinol-palmitate

A wide range of cosmeceutical products are available on the market currently, but evidence to support their use is often lacking in the literature. Specifically, there is a substantial amount of evidence supporting the efficacy of tretinoin in photoaging, but the evidence supporting retinoid-based cosmeceuticals remains sparse. The authors review the current data in the literature related to vitamin A-derived cosmeceutical products and conclude that cosmeceuticals containing retinaldehyde have been shown in large randomized, controlled trials to have the most beneficial effect on aging skin.

Topics: Administration, Topical; Antioxidants; Cosmetics; Dermatologic Agents; Diterpenes; Humans; Keratolytic Agents; Randomized Controlled Trials as Topic; Retinaldehyde; Retinoids; Retinyl Esters; Skin Aging; Tretinoin; Vitamin A

Topics: alpha-Tocopherol; Animals; Diterpenes; Esters; Hydrolysis; Male; Rats; Rats, Inbred Strains; Retinyl Esters; Tocopherols; Vitamin A; Vitamin E; Vitamin E Deficiency; Vitamin K 1

Topics: Adjuvants, Immunologic; Animals; Breast Neoplasms; Carcinogens; Cricetinae; Diterpenes; Female; Humans; Keratoacanthoma; Lung Neoplasms; Male; Mice; Neoplasms; Prostatic Neoplasms; Rats; Retinoids; Retinyl Esters; Tretinoin; Vitamin A

The availability of synthetic vitamin A and its esters in unlimited quantities, has enabled populations around the world, consuming inadequate amounts of this vital micro-nutrient and hence subject to potential loss of sight or other manifestations of vitamin A deficiency, to have hope for a better future life. A technology exists for the preparation of synthetic vitamin A in various application forms. Many commonly-consumed foods may be used as carriers or vehicles of vitamin A to assure deficient populations of a sufficient intake of this antixerophthalmic and anti-infective vitamin.

Topics: Animals; Dietary Fats; Diterpenes; Edible Grain; Food, Fortified; Global Health; Humans; Margarine; Milk; Palmitates; Retinyl Esters; Sodium Chloride; Sodium Glutamate; Sucrose; Tea; Technology, Pharmaceutical; Vitamin A; Vitamin A Deficiency

Dithranol (anthralin) inflammation of forearm skin was completely inhibited by various scavengers of free radicals of the oxygen species. It is concluded that dithranol inflammation is initiated by formation of free radicals; these may act through lipid peroxidation and production of inflammatory endoperoxides or by a more direct mechanism.

Topics: Administration, Topical; Adult; Aged; Anthracenes; Anthralin; Butylated Hydroxyanisole; Diterpenes; Drug Eruptions; Erythema; Female; Free Radicals; Humans; Male; Middle Aged; Retinyl Esters; Vitamin A; Vitamin E

Ubiquitous low-dose methylmercury (MeHg) exposure through an increased fish consumption represents a global public health problem, especially among pregnant women. A plethora of micronutrients presented in fish affects MeHg uptake/distribution, but limited data is available. Vitamin A (VitA), another fish micronutrient is used in nutritional supplementation, especially during pregnancy. However, there is no information about the health effects arising from their combined exposure. Therefore, the present study aimed to examine the effects of both MeHg and retinyl palmitate administered on pregnant and lactating rats in metabolic and redox parameters from dams and their offspring. Thirty Wistar female rats were orally supplemented with MeHg (0,5 mg/kg/day) and retinyl palmitate (7500 µg RAE/kg/day) via gavage, either individually or in combination from the gestational day 0 to weaning. For dams (150 days old) and their offspring (31 days old), glycogen accumulation (hepatic and cardiac) and retinoid contents (plasma and liver) were analyzed. Hg deposition in liver tissue was quantified. Redox parameters (liver, kidney, and heart) were evaluated for both animals. Cytogenetic damage was analyzed with micronucleus test. Our results showed no general toxic or metabolic alterations in dams and their offspring by MeHg-VitA co-administration during pregnancy and lactation. However, increased lipoperoxidation in maternal liver and a disrupted pro-oxidant response in the heart of male pups was encountered, with apparently no particular effects in the antioxidant response in female offspring. GST activity in dam kidney was altered leading to possible redox disruption of this tissue with no alterations in offspring. Finally, the genomic damage was exacerbated in both male and female pups. In conclusion, low-dose MeHg exposure and retinyl palmitate supplementation during gestation and lactation produced a potentiated pro-oxidant effect, which was tissue-specific. Although this is a pre-clinical approach, we recommend precaution for pregnant women regarding food consumption, and we encourage more epidemiological studies to assess possible modulations effects of MeHg-VitA co-administration at safe or inadvertently used doses in humans, which may be related to specific pathologies in mothers and their children.

Topics: Animals; Animals, Newborn; Antioxidants; Catalase; Dietary Supplements; Diterpenes; Female; Glutathione Peroxidase; Glutathione Transferase; Lactation; Liver; Male; Methylmercury Compounds; Oxidation-Reduction; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Retinyl Esters; Superoxide Dismutase; Vitamin A

Topics: Adolescent; Adult; Age Factors; Animals; Child; Child, Preschool; Consumer Product Safety; Cosmetics; Diet; Diterpenes; Female; Humans; Infant; Pregnancy; Recommended Dietary Allowances; Retinyl Esters; Risk Assessment; Risk Factors; Societies, Medical; Toxicity Tests; Vitamin A

According to the European Food Safety Authority, currently, there are no reliable data or robust guidelines available in relation to the micronutrient composition of infant foods. This study evaluated the intake of vitamins A and E of infants from 'ready-to-feed' foods and formulas. Normal phase high performance liquid chromatography was employed for simultaneous quantification of retinyl acetate, retinyl palmitate, α-tocopherol and γ-tocopherol, reverse phase high performance liquid chromatography for the quantification of β-carotene, and UV spectrophotometry for the quantification of carotenoids from selected infant food samples. Based on the results of this study, the estimated total daily intake of vitamin A (retinol equivalents) and vitamin E (α-tocopherol equivalents) from both infant food and formula milk exceed recommendations set by the UK Department of Health. This requires further analysis of risk of exposure, whilst a cause for concern over deficiency might arise when the intake of milk is compromised.

Topics: alpha-Tocopherol; beta Carotene; Chromatography, High Pressure Liquid; Diterpenes; Food, Formulated; Humans; Infant; Infant Food; Micronutrients; Retinyl Esters; United Kingdom; Vitamin A; Vitamin E

A new two-step chemo-enzymatic approach for highly efficient synthesis of all-trans-retinyl palmitate is constructed in this study. In the first step, retinyl acetate as starting material was fully hydrolyzed to retinol by potassium hydroxide. In the hydrolysis system, anhydrous ethanol was the best co-solvent to increase the solubility of retinyl acetate. The addition amounts of 5 M potassium hydroxide and anhydrous ethanol were 8 and 10 mL against 10 g retinyl acetate, respectively, and 100 % hydrolysis rate was obtained. In the second step, esterification was catalyzed by immobilized lipase on macroporous acrylic resin AB-8 using the extracted retinol and palmitic acid as substrates in non-aqueous system. After optimization, the parameters of esterification reaction were confirmed as follows: non-aqueous solvent was selected as n-hexane, washing times of extraction solution was four times, retinol concentration was 300 g/L, substrate molar ratio of retinol to palmitic acid was 1:1.1, the amount of immobilized enzyme was 10 g/L, and the esterification temperature was 30 °C. Under the optimal conditions, this protocol resulted in a 97.5 % yield of all-trans-retinyl palmitate in 700-L reactor. After purification, all-trans-retinyl palmitate was obtained with above 99 % of purity and 88 % of total recovery rate. This methodology provides a promising strategy for the large-scale production of all-trans-retinyl palmitate.

Topics: Attention; Diterpenes; Enzymes, Immobilized; Esterification; Hydrolysis; Lipase; Palmitic Acid; Retinyl Esters; Temperature; Vitamin A

A detailed optimization of dispersive liquid-liquid microextraction (DLLME) was carried out for developing liquid chromatographic (HPLC) techniques, using both fluorescence and atmospheric pressure chemical ionization mass spectrometric (APCI-MS) detection, for the simultaneous analysis of preforms of vitamin A: retinol (R), retinyl acetate (RA), retinyl palmitate (RP) and β-carotene (β-C). The HPLC analyses were carried out using a mobile phase composed of methanol and water, with gradient elution. The APCI-MS and fluorescence spectra permitted the correct identification of compounds in the analyzed samples. Parameters affecting DLLME were optimized using 2 mL of methanol (disperser solvent) containing 150 μL carbon tetrachloride (extraction solvent). The precision ranged from 6% to 8% (RSD) and the limits of detection were between 0.03 and 1.4 ng mL(-1), depending on the compound. The enrichment factor values were in the 21-44 range. Juice samples were analyzed without saponification and no matrix effect was found when using fluorescence detection, so calibration was possible with aqueous standards. However, a matrix effect appeared with APCI-MS, in which case it was necessary to apply matrix-matched calibration. There was great variability in the forms of vitamin A present in the juices, the most abundant ester being retinyl acetate (0.04 to 3.4 μg mL(-1)), followed by the amount of retinol (0.01 to 0.16 μg mL(-1)), while retinyl palmitate was not detected, except in the milk-containing juice, in which RP was the main form. The representative carotenoid β-carotene was present in the orange, peach, mango and multifruit juices in high amounts. The method was validated using two certified reference materials.

Topics: beta Carotene; Beverages; Chromatography, High Pressure Liquid; Diterpenes; Fruit; Least-Squares Analysis; Liquid Phase Microextraction; Mass Spectrometry; Reproducibility of Results; Retinyl Esters; Sensitivity and Specificity; Spectrometry, Fluorescence; Vitamin A

A dissolution test method and an analytical procedure by HPLC were developed and validated for evaluation of the dissolution behavior of dietary supplements tablets containing vitamin A in the forms of retinyl acetate or retinyl palmitate. Seven different commercially available products containing retinyl acetate or retinyl palmitate were selected for this study. A dissolution medium containing 1% (w/v) Octoxynol 9 (Triton X-100) and 1% (w/v) (+)-sodium alpha-ascorbate in 0.05 M phosphate buffer, pH 6.8, was found suitable to ensure sink conditions and chemical stability for both retinyl acetate and retinyl palmitate. Two rotation speeds, 50 and 75 rpm, were evaluated with USP Apparatus 2 and 900 ml dissolution medium. Dissolution profiles were generated over 120 min. Dissolution samples were analyzed with a reversed-phase HPLC method with UV detection at 325 nm. Each product was also assayed for vitamin A content according to USP 32-NF 27. The results from 45 min to the last time point of the dissolution tests performed at 75 rpm were consistent with the Assay results. The dissolution test described here could be proposed as a pharmacopeial standard to assess the performance of tablet formulations containing vitamin A as retinyl esters.

Topics: Calibration; Chromatography, High Pressure Liquid; Dietary Supplements; Diterpenes; Drug Stability; Retinyl Esters; Sensitivity and Specificity; Solubility; Tablets; Vitamin A

A rapid, simple and reproducible normal-phase (NP) high-performance liquid chromatography (HPLC)-diode array detection (DAD) method for simultaneous qualitative and quantitative determination of Vitamin A (retinol acetate and retinol palmitate) and Vitamin E (alpha-tocopherol acetate, alpha-, gamma- and delta-tocopherols) in milk-based infant formulae was developed and validated. The preparation sample was based on protein precipitation and vitamin extraction with ethanol, followed by re-extraction with hexane, while the chromatographic method was based on the use of a short narrow-bore column (50 mm x 2.1 mm; 3 microm particle size), which afforded less solvent consumption and higher mass sensitivity. The method showed acceptable values for precision, recovery and sensitivity, and proved very simple for routine analysis work.

Topics: alpha-Tocopherol; Animals; Chromatography, High Pressure Liquid; Diterpenes; Humans; Infant; Infant Formula; Milk; Reproducibility of Results; Retinyl Esters; Tocopherols; Vitamin A; Vitamin E

Recent work examining vitamin A (VA) status of rhesus monkeys (Macaca mulatta) used as models for human biomedical research has revealed subtoxic hepatic VA concentrations. Livers of marmoset monkeys (Callithrix jacchus), another experimental animal, were also high in VA as was serum retinyl ester concentration. Both species consumed common research diets that provided up to four times the amount of VA (retinyl acetate) as currently recommended by the National Research Council. To further define the effects of chronically high dietary VA as found in many human subpopulations, we analyzed lung and kidney tissues from subtoxic rhesus and marmoset monkeys (n = 10 each) for retinol and retinyl esters. Marmoset kidneys contained 0.88 +/- 0.66 micromol VA/g and was nearly the same as hepatic VA at 1.40 +/- 0.44 micromol/g (p = 0.143). In contrast, rhesus kidney VA concentrations were 0.0100 +/- 0.0032 micromol/g, even though liver reserves were 18.8 +/- 6.4 micromol VA/g (p < 0.0001). Lung tissue VA concentrations, 0.0022 +/- 0.0012 and 0.0061 +/- 0.0025 micromol/g for marmosets and rhesus, respectively, were lower as compared with kidney (p < 0.011). Kidney and lung VA in monkeys with adequate, but not excessive, VA stores have not been determined; hence, interpretation of these findings is limited to tissue retinol and retinyl ester profiles and extrapolation from other species rather than direct comparison to "normal" values.

Topics: Animals; Callithrix; Chromatography, High Pressure Liquid; Diet; Diterpenes; Female; Kidney; Liver; Lung; Macaca mulatta; Male; Retinyl Esters; Vitamin A

The present study was designed to investigate the effect of a one-month feeding of retinyl acetate (RA) on the retinol (ROL), retinyl palmitate (RP) and beta-carotene (BC) levels in the blood, testicles and ovarian follicles of adult Japanese quails. The basal diet (containing vitamin A at 10 x 10(3) IU/kg) was supplemented with 100 x, 500 x and 1000 x 10(3) IU/kg RA in Groups I, II and III in both sexes. Plasma vitamin A levels rose in all groups. The elevations were caused basically by the RP fraction. The ROL concentration increased only slightly, indicating saturation of the blood binding/transport system. Plasma BC was depressed in both sexes. RA feeding resulted in high RP concentration in the genital organs (testicles and ovarian follicles), indicating subclinical hypervitaminosis, while the BC content of genital organs decreased considerably. The retinoid and BC concentration of ovarian follicles (F1-F5) was in the same range, indicating continuous retinoid and carotene transport during the fast maturation period. Retinoid content of the genital organs was higher in layers than in roosters. BC deposition was decreased both in the testicles and in the follicles, indicating a competition between RP and BC for the storage capacity of organs.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Chromatography, High Pressure Liquid; Coturnix; Diterpenes; Female; Male; Ovarian Follicle; Retinyl Esters; Sex Characteristics; Testis; Vitamin A

We examined whether vitamin A improved mucosal immune depression in mice with wasting protein deficiency. In male C3H/HeN mice fed a semi-purified 1% protein diet for 2 wk, plasma retinol and immunoglobulin A (IgA) concentrations in the small intestinal mucosa were 50 and 55%, respectively, of those in mice fed a semi-purified 20% protein diet, (P < 0.05). Daily supplementation of 0.3 mg of retinyl acetate to protein-deficient mice for 2 wk increased the plasma retinol level to the value in the protein-sufficient mice. However, 1 mg/d of retinyl acetate was required to prevent the decline of the IgA level caused by the protein deficiency. Mice fed the low-protein diet had lower concentrations of IL-4 and IL-5 in the small intestinal mucosa and fewer IL-4- and IL-5-containing cells in the lamina propria (P < 0. 05). Retinyl acetate (1 mg) significantly restored the IL-5 level and the number of IL-4- and IL-5-containing cells. After immunization with 20 microg of cholera toxin (CT), the intestinal mucosa of protein-deficient mice contained significantly less CT-specific IgA than control mice. Treatment with 1 mg of retinyl acetate prevented the decline of anti-CT IgA level in the protein-deficient mice, improving their survival rate after an exposure to 0.1 mg of CT. These results suggest that large oral supplements of vitamin A may preserve mucosal IgA level during protein malnutrition, possibly by stimulating Th2 cytokine production and thereby, inducing resistance against infection.

Topics: Animals; Cholera Toxin; Diterpenes; Immunoglobulin A; Immunohistochemistry; Interleukin-4; Interleukin-5; Intestinal Mucosa; Intestine, Small; Male; Mice; Mice, Inbred C3H; Nutritional Status; Protein Deficiency; Retinyl Esters; 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

The transport of subcutaneously injected retinyl acetate (RA, 100,000 IU/mouse, 105,470 nM) was investigated in male ICR mice (10-week-old) at 0, 3, 6, 12, 18, 24 and 72 hr after a single injection. The retinol and retinyl palmitate levels of liver homogenates, bile in the gallbladder and serum from peripheral blood were measured by high performance liquid chromatography (HPLC) method. Retinyl palmitate in the lipid droplets of hepatocytes and Ito cells was localized by a modified gold chloride staining method. Accumulation of retinyl palmitate peaked at 12 hr post-injection and decreased thereafter until 24 hr post-injection. Fluorescence microscopy revealed many fluorescent vitamin A-containing lipid droplets in hepatocytes around central veins at 12 hr post-injection, but such droplets were not observed in the vehicle control mice or at in the RA-injected mice after 18 hr of injection. Electron microscopic observation also indicated that many retinyl esters-containing lipid droplets were observed in hepatocytes around the central veins at 12 hr post-injection, but no droplets were seen in the controls or 18 hr post-injection. The retinyl palmitate levels in liver homogenates assessed by HPLC decreased from 12 to 24 hr post-injection and increased significantly in bile, while retinol in liver homogenates and serum markedly increased. One of the morphological alterations was intense vacuolization in hepatocyte cell cords from the portal toward the central vein observed at 24 hr post-injection. Transitional lipid droplets between vacuoles and lipid droplets were identified in those hepatocytes. These results of HPLC analysis of retinol and retinyl palmitate in liver homogenates, serum, and bile, together with the results of gold chloride staining suggested that subcutaneously injected RA was first incorporated in hepatocytes at 12 hr and then partially metabolized through vacuoles, transferred into the blood and secreted into the bile over a 24 hr period. Many retinyl esters-containing lipid droplets were visualized in Ito cells at 72 hr post-injection. Most of vitamin A in the liver homogenates measured by HPLC was retinyl palmitate. Therefore, the contents in those lipid droplets might be retinyl palmitate.

Topics: Animals; Bile; Cells, Cultured; Chromatography, High Pressure Liquid; Diterpenes; Gallbladder; Liver; Male; Mice; Mice, Inbred ICR; Retinyl Esters; Tissue Distribution; Vacuoles; Vitamin A

Biological functions of retinoids in the vertebrate retina include the role of 11-cis retinaldehyde as visual pigment chromophore, and possible effects of retinoic acid in histogenesis and cell survival. Qualitative and quantitative regulation of retinoid availability for these complex processes could involve several cell types, including retinal pigment epithelium, Müller glia and retinal photoreceptors and non-photoreceptor neurons; their relative contributions, however, have not been fully elucidated. Using purified cultures, we have carried out a study of cell-type-specific metabolism and storage of retinoids in chick embryo retinal photoreceptors and other neuronal cells, as compared to those of retinal glia. Retinal glia were found to synthesize both retinoic acid and retinyl esters, and to hydrolyse the latter; they also displayed retinol dehydrogenase activities. Cultured neurons and photoreceptors also synthesized and hydrolysed retinyl esters; their capacity for retinaldehyde synthesis from a retinol or retinyl ester substrate suggested the presence of retinol dehydrogenase activity. Retinoic acid was not synthesized in differentiated neuronal cultures, although some synthesis was detectable at early culture stages when the cells were still morphologically undifferentiated. These findings indicate that cell-type-specific metabolic activities are expressed during retinal cell differentiation in vitro, and that embryonic retinal photoreceptors and nonphotoreceptor neurons are active participants in the metabolism and storage of retinoids.

Topics: Animals; Cells, Cultured; Chick Embryo; Diterpenes; Neuroglia; Neurons; Photoreceptor Cells; Retina; Retinaldehyde; Retinoids; Retinyl Esters; Tretinoin; Vitamin A

An efficient protocol is described for the study of the kinetics of retinyl esters in whole plasma and several lipoprotein fractions following the consumption of an oral fat load containing vitamin A (retinol). To allow for a more complete characterization of the kinetics of retinyl esters in different lipoprotein fractions, a simplified two-step ultracentrifugation procedure is reported for the efficient and reproducible isolation of triglyceride-rich chylomicrons from nonfasting subjects, VLDL-sized lipoprotein particles, and the triglyceride-poor lipoprotein fraction. The present method for the determination of retinyl esters is based on the direct application of the lipid fraction onto a normal phase HPLC column without requiring the lipid extract to be desiccated and resolubilized. All of the commonly occurring esters of retinol elute as a single peak with a retention time of 1.6-1.8 min followed by retinyl acetate (serving as the internal standard) and retinol with retention times of 2-2.5 min and 5-5.5 min, respectively. With this system, a new sample can be processed every 10 min and a complete set of 60 samples from a typical oral fat load can analyzed in one working day with minimal technical interaction. By normalizing to the area under the internal standard to correct for variability in the injected volume, the coefficient of variability for the concentration retinyl esters within a single run is less than 5% and less than 10% between runs.

Topics: Chemical Fractionation; Chromatography, High Pressure Liquid; Diterpenes; Eating; Humans; Lipids; Lipoproteins; Retinyl Esters; Vitamin A

Topics: Animals; Biological Availability; Diterpenes; Graft Rejection; Intestinal Absorption; Intestine, Small; Rats; Rats, Inbred Lew; Rats, Inbred Strains; Retinyl Esters; Short Bowel Syndrome; Transplantation, Homologous; Transplantation, Isogeneic; Vitamin A

The transfer of retinoic acid, retinyl acetate, and retinyl palmitate between single unilamellar vesicles was studied by resonance energy transfer. The retinoic acid transfers spontaneously between single unilamellar vesicles with a first order rate constant of 9.6 s-1 at 15 degrees C and pH 7.4. At 30 degrees C, the transfer rate was 3.5 times faster than that at 10 degrees C. At pH 7.4, the transfer rate was almost 2 orders of magnitude faster than that observed at pH 1.6. Increasing the concentration of NaCl decreased the retinoic acid transfer rate significantly. Retinyl acetate transfers with a rate constant of 0.15 s-1, but no spontaneous transfer of retinyl palmitate was observed over 60 min. The evidence supports the proposal that retinoic acid and retinyl acetate transfer between single unilamellar vesicles occur via the aqueous phase. In contrast, no spontaneous transfer of retinyl palmitate was observed. However, linear free energy relationships and the thermodynamic parameters for retinyl acetate transfer permit the calculation of rate constant for retinyl palmitate transfer.

Topics: Diterpenes; Energy Transfer; Kinetics; Liposomes; Osmolar Concentration; Phosphatidylcholines; Phosphatidylethanolamines; Retinyl Esters; Spectrometry, Fluorescence; Thermodynamics; Tretinoin; Vitamin A

Vitamin A (retinol) and some of its analogs exhibited varying degrees of inhibition on induced iron and ascorbic acid lipid peroxidation of rat brain mitochondria. Malonyldialdehyde production was used as an index of the extent of in vitro lipid peroxidation. The fat-soluble vitamins retinol, retinol acetate, retinoic acid, retinol palmitate, and retinal at concentrations between 0.1 and 10.0 mmol/L inhibited brain lipid peroxidation. Retinol and retinol acetate were the most effective inhibitors. It is concluded from this study that retinol and its analogs can be considered as potential antioxidant factors, more potent than some of the well-known antioxidants such as alpha-tocopherol and butylated hydroxytoluene.

Topics: Animals; Ascorbic Acid; Brain; Diterpenes; Ferrous Compounds; Free Radicals; Lipid Peroxidation; Male; Malondialdehyde; Mitochondria; Rats; Rats, Inbred Strains; Retinaldehyde; Retinyl Esters; Tretinoin; 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

Post-mortem concentrations of hepatic retinol and retinyl esters were determined in 40 subjects aged over 65 years to assess the effects of disease and malnutrition on vitamin A reserves. Three groups of patients (mean age 79.6 years) were studied: (1) previously healthy, (2) chronically ill, (3) chronically ill and wasted. There was no significant difference in height or age between the groups, but group 3 was lighter than both group 1 (P less than 0.001) and group 2 (P less than 0.05). Free retinol and retinyl esters were measured by high pressure liquid chromatography, and the total hepatic retinol calculated. Analysis of variance showed that the three groups differed significantly (P less than 0.02) with regard to total retinol, retinyl palmitate and total retinyl ester content.

Topics: Aged; Aged, 80 and over; Animals; Autopsy; Chromatography, High Pressure Liquid; Chronic Disease; Diterpenes; Female; Humans; Liver; Male; Nutrition Disorders; Retinoids; Retinyl Esters; Vitamin A; Vitamin A Deficiency

The four most important non-specific carboxylesterases from rat liver were assayed for their ability to hydrolyse retinyl esters. Only the esterases with pI 6.2 and 6.4 (= esterase ES-4) are able to hydrolyse retinyl palmitate. Their specific activities strongly depend on the emulsifier used (maximum rate: 440 nmol of retinol liberated/h per mg of esterase). Beside retinyl palmitate, these esterases cleave palmitoyl-CoA and monoacylglycerols with much higher rates, as well as certain drugs (e.g. aspirin and propanidid). However, no transacylation between palmitoyl-CoA and retinol occurs. Retinyl acetate also is a substrate for the above esterases and for another one with pI 5.6 (= esterase ES-3). Again the emulsifier influences the hydrolysis by these esterases (maximum rates: 475 nmol/h per mg for ES-4 and 200 nmol/h per mg for ES-3). Differential centrifugation of rat liver homogenate reveals that retinyl palmitate hydrolase activity is highly enriched in the plasma membranes, but only moderately so in the endoplasmic reticulum, where the investigated esterases are located. Since the latter activity can be largely inhibited with the selective esterase inhibitor bis-(4-nitrophenyl) phosphate, it is concluded that the esterases with pI 6.2 and 6.4 (ES-4) represent the main retinyl palmitate hydrolase of rat liver endoplasmic reticulum. In view of this cellular localization, the enzyme could possibly be involved in the mobilization of retinol from the vitamin A esters stored in the liver. However, preliminary experiments in vivo have failed to demonstrate such a biological function.

Topics: Animals; Carboxylic Ester Hydrolases; Centrifugation; Diterpenes; Endoplasmic Reticulum; Hydrolysis; Liver; Microsomes, Liver; Palmitoyl Coenzyme A; Rats; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Retinyl Esters; Vitamin A

The effect of vitamin A palmitate (VAP), vitamin A acetate (VAA), 2,3-tert-butyl-4-hydroxyanisole, and 2,6-di-tert-butyl-p-cresol (BHT) on mutagenesis induced by 7,12-dime-thylbenz[a]anthracene (DMBA) was examined in a human epithelial-like cell line. Cultures were exposed to DMBA with or without the antioxidant compound, and mutation frequencies were determined by selection against diphtheria toxin. A clear inhibition of mutagenesis was observed particularly with VAA and BHT.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Antioxidants; Cell Line; Diterpenes; Humans; Mutation; Retinyl Esters; Vitamin A

The vitamin A analogs retinoic acid and retinol caused a significant increase in concanavalin A-induced agglutination of human erythrocytes, while its esters, retinyl acetate and retinyl palmitate, were found to be ineffective. The effect of membrane labilizers and stabilizers on the enhancement of agglutination as well as the properties of the model system employed showed that the action of vitamin A is due to a direct action on cell membrane and is not mediated by the release of lysosomal proteases into the medium, a hypothesis proposed by earlier workers.

Topics: Concanavalin A; Diterpenes; Erythrocytes; Hemagglutination; Humans; Retinyl Esters; Tretinoin; 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

The influence of all-trans- and 13-cys-methylretinoate on antibacterial and antiviral immunity was studied in experiments on noninbred C57Bl/6 and (CBA X C57Bl/6) F1 mice. All-trans-methylretinoate was shown to stimulate the production of antibodies to E. coli antigens, with the effect being dose-dependent. At the same time both compounds inhibited the production of inhibitors, interferon and antibodies to influenza virus.

Topics: Animals; Antibodies, Bacterial; Antibodies, Viral; Antibody Formation; Antiviral Agents; Diterpenes; Escherichia coli; Female; Interferons; Male; Mice; Orthomyxoviridae; Retinyl Esters; Tretinoin; Vitamin A

Topics: Animals; Chromatography, High Pressure Liquid; Diterpenes; Female; Fenretinide; Liver; Mice; Rats; Rats, Inbred Strains; Retinoids; Retinyl Esters; Tretinoin; Vitamin A

Invasion of chick chorioallantoic membrane (CAM) organ cultures by rat 3Y1 cells transformed by the highly oncogenic human adenovirus type 12 (3Y1/12-10 cells) was inhibited by several retinoids tested. The anti-invasive activity of the retinoids was dependent on retinoid concentration and continuous (4 d) exposure of the CAM. The 50% retinoid dose (dose effective in achieving a response in half of the organ cultures) that inhibited invasion was 0.85 micrograms/ml of retinol palmitate, 0.39 micrograms/ml of retinoic acid, or 0.16 micrograms/ml of retinol acetate. This dose was of the same order of magnitude as that which induced CAM differentiation, and was three- to fourfold less than the dose that caused cytotoxic damage of CAM. In addition, the retinoids inhibited 3Y1/12-10 cell growth by approximately 40% at levels over 10-fold higher than those needed for anti-invasion activity. The findings suggest that the anti-invasive activity of retinoids was at least partly due to direct induction of cell differentiation of the CAM host tissue.

Topics: Adenoviruses, Human; Allantois; Animals; Cell Differentiation; Cell Division; Cell Transformation, Neoplastic; Cell Transformation, Viral; Chick Embryo; Chorion; Diterpenes; Extraembryonic Membranes; Neoplasm Invasiveness; Organ Culture Techniques; Rats; Retinoids; Retinyl Esters; Tretinoin; Vitamin A

The effect of vitamin A on cyclophosphamide mutagenicity was measured both in vitro and in vivo. In the Ames test in Salmonella typhimurium TA1535 with mouse-liver S-9 mix, the addition of retinol, retinyl acetate or retinyl palmitate caused a dose-dependent inhibition of cyclophosphamide mutagenicity. In the micronucleus test in male NMRI mice fed low, normal or high levels of vitamin A, the induction of micronuclei in bone marrow by an ip dose of cyclophosphamide was unaffected by vitamin A status. Thus, this study provides no evidence that activation of a procarcinogen in the liver or bone marrow of mice can be modified by vitamin A. One of the possible reasons for the observed absence of inhibition by vitamin A in vivo may be a lack of correlation between the oral dose of retinoid and the resulting level of vitamin A in the bone marrow. The difference between results in vitro and in vivo may also have been due to a difference in the availability and potency of added vitamin A in vitro compared with the forms absorbed and stored in vivo.

Topics: Animals; Body Weight; Bone Marrow; Cell Nucleus; Cyclophosphamide; Diterpenes; In Vitro Techniques; Liver; Male; Mice; Microsomes, Liver; Mutagenicity Tests; Mutagens; Retinyl Esters; Salmonella typhimurium; Vitamin A

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

These experiments describe further investigations into the effects of vitamin A on regenerating limbs. The effects of different retinoids, the time of administration, concentration of vitamin A and histological, autoradiographic and histochemical studies are reported. The most obvious result of vitamin A treatment is to cause proximal elements to regenerate from distal amputation levels, that is to cause serial reduplication of pattern in the proximodistal axis. Retinoic acid was the most potent of the analogues tested and longer times of administration or higher concentrations cause a greater amount of serial reduplication. Various tissue changes have been found which include the inhibition of cell division, loss of cartilage metachromasia, changes in the mucous-secreting properties of the epidermis and an increased packing in the blastemal cells. The significance of these cellular effects in relation to the pattern-formation changes is discussed.

Topics: Ambystoma mexicanum; Animals; Connective Tissue; Diterpenes; Dose-Response Relationship, Drug; Forelimb; Mitotic Index; Morphogenesis; Regeneration; Retinyl Esters; Time Factors; Tretinoin; Vitamin A

We treated experimental corneal epithelial wounds in rabbits with topical retinoids. Treatment with 0.1% all-trans-retinoic acid three times per day resulted in a 21% increase in the healing rate compared to the control eyes. Treatment five times a day resulted in a 35% increase in healing rate. Treatment with topical retinoic acid also promoted corneal deturgescence. Retinyl palmitate, retinyl acetate, retinol, and 13-cis-retinoic acid had no effect on corneal wound healing. These data suggested that topically applied all-trans-retinoic acid may be effective in promoting corneal healing after surgery and in the treatment of persistent and recurring corneal epithelial defects.

Topics: Administration, Topical; Animals; Cornea; Corneal Injuries; Diterpenes; Rabbits; Retinyl Esters; Tretinoin; Vitamin A; Wound Healing

A rapid specific, microdetermination of the major human blood carotenoids by high performance liquid chromatography (HPLC) separation and quantitation at 466 nm is detailed in this paper. Serum retinyl esters can also be quantified utilizing the same separation procedure but detected at 325 nm. One hundred microliters of deproteinated serum were extracted with chloroform and injected on a reverse-phase column. Separation occurred within 16 min for all compounds of interest employing a mobile solvent of MeOH/AcN/CHCl3 (47:47:6). All compounds were quantified at the wavelengths cited by integrated peak areas using retinyl acetate as a daily standard. Analysis of serum from a hypercarotenemic anorexia nervosa patient and a person suffering from hypervitaminosis A are presented as examples of the clinical application of this procedure.

Topics: beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Diterpenes; Freezing; Humans; Lycopene; Retinyl Esters; Vitamin A

A study has been made of the effects of retinoic acid, retinal, retinol, retinyl palmitate and retinyl acetate on HeLa cell viability. The results obtained show that (i) these cells seem to be more resistant to vitamin A than other cell cultures; (ii) the various vitamin A compounds differ in their inhibitory action on HeLa cells; (iii) the effects of retinoic acid, retinal, retinol and retinyl acetate are cytotoxic, those of retinyl palmitate are always cytolytic.

Topics: Cell Survival; Diterpenes; HeLa Cells; Humans; Retinaldehyde; Retinyl Esters; Tretinoin; Vitamin A

Serum and milk samples from mares and serum samples from their foals were taken at parturition and on d 1, 2, 4, 7, 14 and 21 postpartum. The samples were assayed for retinyl (r.) palmitate, r. acetate and retinol by high performance liquid chromatography. Peak vitamin A activity in milk occurred 1 d postpartum and preceded by 3 d the maximum vitamin A activity in foal serum and the lowest vitamin A activity in the mare serum. Mare serum contained approximately a 65:35 ratio of retinol:r. palmitate and less than 1% r. acetate. Retinyl palmitate was the predominant form of vitamin A in milk until 2 to 3 d postpartum, when r. acetate became and remained the predominant form. Retinol represented less than 1% of the milk vitamin A. A significant quantity of r. acetate was present in the foal sera at 4 d of age, but thereafter serum r. acetate appeared unaffected by the increasing r. acetate levels in the mare milk.

Topics: Animals; Animals, Newborn; Chromatography, High Pressure Liquid; Colostrum; Diterpenes; Female; Horses; Milk; Postpartum Period; Pregnancy; Retinyl Esters; Vitamin A

Topics: Chemistry, Pharmaceutical; Diterpenes; Health Services; Pharmacy; Research; Retinyl Esters; Spectrophotometry; Vitamin A