retinaldehyde and Vitamin-A-Deficiency

Vitamin A deficiency can cause human pathologies that range from blindness to embryonic malformations. This diversity is due to the lack of two major vitamin A metabolites with very different functions: the chromophore 11-cis-retinal (vitamin A aldehyde) is a critical component of the visual pigment that mediates phototransduction, while the signaling molecule all-trans-retinoic acid regulates the development of various tissues and is required for the function of the immune system. Since animals cannot synthesize vitamin A de novo, they must obtain it either as preformed vitamin A from animal products or as carotenoid precursors from plant sources. Due to its essential role in the visual system, acute vitamin A deprivation impairs photoreceptor function and causes night blindness (poor vision under dim light conditions), while chronic deprivation results in retinal dystrophies and photoreceptor cell death. Chronic vitamin A deficiency is the leading cause of preventable childhood blindness according to the World Health Organization. Due to the requirement of vitamin A for retinoic acid signaling in development and in the immune system, vitamin A deficiency also causes increased mortality in children and pregnant women in developing countries. Drosophila melanogaster is an excellent model to study the effects of vitamin A deprivation on the eye because vitamin A is not essential for Drosophila development and chronic deficiency does not cause lethality. Moreover, genetic screens in Drosophila have identified evolutionarily conserved factors that mediate the production of vitamin A and its cellular uptake. Here, we review our current knowledge about the role of vitamin A in the visual system of mammals and Drosophila melanogaster. We compare the molecular mechanisms that mediate the uptake of dietary vitamin A precursors and the metabolism of vitamin A, as well as the consequences of vitamin A deficiency for the structure and function of the eye.

Topics: Animals; Drosophila melanogaster; Mammals; Photoreceptor Cells; Retina; Retinal Pigment Epithelium; Retinaldehyde; Tretinoin; Vision, Ocular; Visual Perception; Vitamin A; Vitamin A Deficiency

Aging of skin is an intricate biological process consisting of two types. While intrinsic or chronological aging is an inevitable process, photoaging involves the premature aging of skin occurring due to cumulative exposure to ultraviolet radiation. Chronological and photoaging both have clinically differentiable manifestations. Various natural and synthetic retinoids have been explored for the treatment of aging and many of them have shown histological and clinical improvement, but most of the studies have been carried out in patients presenting with photoaged skin. Amongst the retinoids, tretinoin possibly is the most potent and certainly the most widely investigated retinoid for photoaging therapy. Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis associated with retinoid therapy limit their acceptance by patients. This problem is more prominent with tretinoin and tazarotene whereas other retinoids mainly represented by retinaldehyde and retinol are considerably less irritating. In order to minimize these side effects, various novel drug delivery systems have been developed. In particular, nanoparticles have shown a good potential in improving the stability, tolerability and efficacy ofretinoids like tretinoin and retinol. However, more elaborate clinical studies are required to confirm their advantage in the delivery of topical retinoids.

Topics: Adapalene; Dermatologic Agents; Dermis; Epidermis; Humans; Naphthalenes; Nicotinic Acids; Retinaldehyde; Retinoids; Skin Aging; Treatment Outcome; Tretinoin; Vitamin A Deficiency

Topics: Animals; Carrier Proteins; Cell Differentiation; Chemical Phenomena; Chemistry; Epithelium; Female; Growth; Humans; Isomerism; Male; Neoplasms; Pregnancy; Receptors, Retinoic Acid; Reproduction; Retinal Pigments; Retinaldehyde; Retinol-Binding Proteins; Skin Diseases; Structure-Activity Relationship; Tretinoin; Vitamin A; Vitamin A Deficiency

Topics: Animals; Apolipoproteins; Female; Genital Diseases, Female; Genital Diseases, Male; Glycoproteins; Growth; Humans; Lipid Metabolism; Lipoproteins; Male; Membrane Proteins; Molecular Biology; Night Blindness; Photoreceptor Cells; Retinal Pigments; Retinaldehyde; Vitamin A; Vitamin A Deficiency; Xerophthalmia

A survey is given concerning recent realizations of importance and metabolism of vitamin A in man and experimental animals. The transport of vitamin A from the small intestine takes place in form of esters by inclusion in chylomicrons and lipoproteins. A higher content in the blood plasma over a longer period evokes toxic effects. In the liver one part of the vitamin A in form of an ester with binding to lipoproteins is accumulated, one part is - according to the need - associated with a vitamin-A-binding protein, which forms complexes with prealbumin molecules and transports the vitamin to the various places of effect. With the help of the receptor proteins the vitamin A is included in the cells, in which it is effective and is transported into the vitamin-A-aldehyde and the vitamin-A-acid. The vitamin A and the vitamin-A-acid are transported into the cell nuclei with the help of receptor-proteins and play a role in the differentiation of the tissues and in the regulation of the synthesis of RNA. When a deficit or an abundance of vitamin A is present in the early phase of pregnancy malformations in the fetuses appear. The vitamin A and structure-similar connections have an inhibiting effect on the development of tumours.

Topics: Animals; Biological Transport; Birds; Carotenoids; Carrier Proteins; Chylomicrons; Congenital Abnormalities; Female; Fishes; Humans; Lipoproteins; Lung Neoplasms; Male; Mammals; Pregnancy; Pregnancy Trimester, First; Retinaldehyde; RNA; Smoking; Tretinoin; Vitamin A; Vitamin A Deficiency

Retinol dehydrogenase 11 (RDH11) is a microsomal short-chain dehydrogenase/reductase that recognizes all-

Topics: Animals; beta Carotene; Diet; Female; Gene Expression; Homeostasis; Male; Mice; Mice, Knockout; Microsomes; Microsomes, Liver; Oxidoreductases; Retinaldehyde; Retinol-Binding Proteins, Plasma; Signal Transduction; Testis; Vitamin A; Vitamin A Deficiency

3, 4-Didehydroretinol (DR) metabolism was previously followed in vitamin A (VA)-replete lactating sows. This study followed DR appearance and clearance after dosage in serum and milk during 2 lactation cycles in sows (n = 8) fed VA-free feed for 3 gestation-lactation cycles. During lactations 2 and 3, 35 μmol 3, 4-didehydroretinyl acetate was given orally after overnight food deprivation. Blood and milk were collected at 0, 1.5, 3, 5, 7, 9, 16, 24, 36, 48, 60, and 72 h; livers were obtained at kill. Samples were analyzed for DR, retinol (R), and 3, 4-didehydroretinyl esters. During lactations 2 and 3, the 5-h serum DR:R ratios were 0.028 ± 0.017 and 0.069 ± 0.042, respectively, and serum R concentrations were 0.75 ± 0.23 and 0.86 ± 0.37 μmol/L, respectively. The DR:R ratio and serum R were 0.018 ± 0.013 and 0.94 ± 0.12 μmol/L, respectively, in VA-replete sows from the same herd. After lactation 3, liver VA was 0.23 ± 0.05 μmol/g, indicating low-normal VA status. Serum DR area-under-the curve from 0 to 48 h increased as liver stores decreased. Thirteen to 23% of DR dose was secreted into milk, consistent with VA-replete sows. Milk DR concentrations were greater during lactation 3 than 2. Peak concentration occurred earlier and the half-life was shorter for milk DR in the more VA-depleted sows. The milk and serum DR:R were correlated from 3 to 9 h (r = 0.70; P < 0.0001) and increased as VA stores decreased regardless of serum R concentration. Milk DR:R may replace serum measurements during lactation.

Topics: Animals; Area Under Curve; Female; Lactation; Milk; Retinaldehyde; Swine; Vitamin A; Vitamin A Deficiency

Hepatic GK (glucokinase) plays a key role in maintaining glucose homoeostasis. Many stimuli regulate GK activity by controlling its gene transcription. We hypothesized that endogenous lipophilic molecules modulate hepatic Gck expression. Lipophilic molecules were extracted from rat livers, saponified and re-constituted as an LE (lipophilic extract). LE synergized with insulin to induce primary hepatocyte, but not beta-cell, Gck expression in an SREBP-1c (sterol-regulatory-element-binding protein-1c)-independent manner. The dramatic induction of Gck mRNA resulted in a significant increase in GK activity. Subsequently, the active molecules were identified as retinol and retinal by MS after the purification of the active LE fractions. Retinoids synergized with insulin to induce Gck expression by the activation of both RAR [RA (retinoic acid) receptor] and RXR (retinoid X receptor). Inhibition of RAR activation completely abolished the effect of retinal. The hepatic GK specific activity and Gck mRNA levels of Zucker lean rats fed with a VAD [VA (vitamin A)-deficient] diet were significantly lower than those of rats fed with VAS (VA-sufficient) diet. Additionally, the hepatic Gck mRNA expression of Sprague-Dawley rats fed with a VAD diet was lower than that of rats fed with VA-marginal, -adequate or -supplemented diets. The reduced expression of Gck mRNA was increased after an intraperitoneal dose of RA in VAD rats. Furthermore, an intravenous injection of RA rapidly raised hepatic Gck expression in rats fed with a VAS control diet. Understanding the underlying mechanism that mediates the synergy may be helpful for developing a treatment strategy for patients with diabetes.

Topics: Animals; Cells, Cultured; Chemical Fractionation; Enzyme Induction; Glucokinase; Hepatocytes; Insulin; Insulin-Secreting Cells; Liver; Rats; Rats, Sprague-Dawley; Receptors, Retinoic Acid; Retinaldehyde; Retinoic Acid Receptor alpha; Retinoid X Receptors; Retinoids; RNA Stability; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Tissue Extracts; Vitamin A; Vitamin A Deficiency

Vitamin A, a naturally occuring antioxidant micronutrient, has immunomodulating effect in patients with immunodeficiency, including an influence on cytokine production and lymphocyte growth and functions. Vitamin A deficiency is associated with a shift from type 2 cytokines to predominantly type 1 cytokines. The aims of this study were to determine Vitamin A status in Common variable immunodeficiency (CVID) patients and the relationship between Vitamin A status and cytokines production. Serum Vitamin A, neopterin, TNF-alpha, IL-2, IL-4, and IL-10 levels were determined in 19 CVID patients and 15 healthy children. Effects of 9-cis retinal, Vitamin A derivative, on cytokines (TNF-alpha, IL-2, IL-4 and IL-10) production in lymphocytes were tested in vitro condition using lymphocyte cultures obtained from CVID patients and healthy children.Serum Vitamin A level in CVDI patients was, 21.1+/- 1.5 microg/dL, significantly (p < 0.001) lower than the value, 35.7+/- 1.8 microg/dL, observed in healthy children. Serum neopterin level in the patients was, 9.8+/- 2.9 nmol/L, higher (p < 0.05) than the value, 3.9+/- 0.7 nmol/L, observed in control group. Common variable immunodeficiency patients, serum IL-4 level was significantly (p < 0.05) lower than the value observed for healthy children. Serum TNF-alpha, IL-2 and IL-10 levels were similar in the patients and healthy children. Vitamin A derivative, 9-cis retinal, increased TNF-alpha and IL-4 production in cultured mononuclear cells obtained from control and CVID patients. Vitamin A derivative, also, increased IL-2 and Il-4 production in cultured mononuclear cells obtained from CVID patients. These results show that CVID patients have low serum Vitamin A levels and high serum neopterin levels. A supplementation with Vitamin A may have role in downregulation of inflammatory responses in CVID patients.

Topics: Adolescent; Adult; Case-Control Studies; Cells, Cultured; Child; Child, Preschool; Common Variable Immunodeficiency; Cytokines; Diterpenes; Down-Regulation; Female; Humans; Interleukin-4; Leukocytes, Mononuclear; Lymphocytes; Male; Retinaldehyde; Tumor Necrosis Factor-alpha; Vitamin A; Vitamin A Deficiency

To determine the role played by keratinocyte transglutaminase (TG1, TG(K)) in the abnormal keratinization of the cornea.. Vitamin A-deficient rats were produced as a model of severe dry eyes, and the expression of the mRNA and the enzyme activity of TG1 were examined in the corneas. The envelope proteins and keratins of cornified cells were also examined immunohistochemically.. The expression and enzyme activity of TG1 mRNA on the ocular surface were significantly upregulated as the vitamin A deficiency developed. As the TG1 expression was upregulated, involucrin, loricrin, and keratin 10 began to be expressed on the epithelial cells of the cornea.. Upregulation of TG1 expression followed by the appearance of the envelope proteins and keratin10 in cornified cells indicated that TG1 is involved in the abnormal keratinization of the cornea.

Topics: Animals; Blotting, Northern; Cornea; Disease Models, Animal; Dry Eye Syndromes; Epithelial Cells; Gene Expression Regulation, Enzymologic; Immunoenzyme Techniques; Keratin-10; Keratins; Membrane Proteins; Protein Precursors; Rats; Rats, Sprague-Dawley; Retinaldehyde; RNA, Messenger; Transglutaminases; Up-Regulation; Vitamin A; Vitamin A Deficiency

Influence of vitamin A (retinol) on growth depends on its sequential oxidation to retinal and then to retinoic acid (RA), producing a ligand for RA receptors essential in development of specific tissues. Genetic studies have revealed that aldehyde dehydrogenases function as tissue-specific catalysts for oxidation of retinal to RA. However, enzymes catalyzing the first step of RA synthesis, oxidation of retinol to retinal, remain unclear because none of the present candidate enzymes have expression patterns that fully overlap with those of aldehyde dehydrogenases during development. Here, we provide genetic evidence that alcohol dehydrogenase (ADH) performs this function by demonstrating a role for Adh3, a ubiquitously expressed form. Adh3 null mutant mice exhibit reduced RA generation in vivo, growth deficiency that can be rescued by retinol supplementation, and completely penetrant postnatal lethality during vitamin A deficiency. ADH3 was also shown to have in vitro retinol oxidation activity. Unlike the second step, the first step of RA synthesis is not tissue-restricted because it is catalyzed by ADH3, a ubiquitous enzyme having an ancient origin.

Topics: Alcohol Dehydrogenase; Alcohol Oxidoreductases; Animals; Cytosol; Genotype; Mice; Mice, Transgenic; Mutation; Oxygen; Retinaldehyde; Time Factors; Tretinoin; Vitamin A; Vitamin A Deficiency

To investigate the role of retinal-based pigments (opsins) in circadian photoreception in mice, animals mutated in plasma retinol binding protein were placed on a vitamin A-free diet and tested for photic induction of gene expression in the suprachiasmatic nucleus. After 10 months on the vitamin A-free diet, the majority of mice contained no detectable retinal in their eyes. These mice demonstrated fully intact photic signaling to the suprachiasmatic nucleus as measured by acute mPer mRNA induction in the suprachiasmatic nucleus in response to bright or dim light. The data suggest that a non-opsin pigment is the primary circadian photoreceptor in the mouse.

Topics: Animals; Circadian Rhythm; Crosses, Genetic; Female; Homozygote; In Situ Hybridization; Male; Mice; Mice, Inbred C57BL; Photoreceptor Cells, Vertebrate; Reference Values; Retinaldehyde; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Signal Transduction; Suprachiasmatic Nucleus; Time Factors; Vitamin A Deficiency

beta-Carotene might be converted oxidatively to vitamin A- active products in animals by the following three possible routes: 1) central cleavage, 2) sequential excentric cleavage or 3) random cleavage. Central cleavage is strongly favored by stoichiometric studies with tissue homogenates in vitro. To examine the relative importance of these pathways in rats in vivo, an oral dose (5.6 micromol) of all-trans beta-carotene in oil was given to vitamin A-deficient (-A) and to vitamin A-sufficient (+A) adult female Sprague-Dawley rats. Serum and several tissues were analyzed before and 3 h after dosing. The primary products of beta-carotene found in the intestine, serum and liver were retinol, retinyl esters and retinoic acid. Two minor oxidation products of beta-carotene, namely, 5,6-epoxy-beta-carotene and a partially characterized hydroxy-beta-carotene, were present in the stomach and its contents as well as in intestinal preparations. In the intestine, including its contents, of -A rats, very minor amounts of 5,6-epoxyretinyl palmitate and of beta-apocarotenals (8', 10', 12', 14') were identified. The total amount of the beta-apocarotenoids, however, was <5% of the retinoids formed in the intestine from beta-carotene during the same period. Another beta-carotene derivative, with a spectrum similar to that of semi-beta-carotenone, citranaxanthin and beta-apo-6'-carotenal, was also found in the intestinal extract of a -A rat. beta-Apocarotenals, beta-apocarotenols, beta-apocarotenyl esters and beta-apocarotenoic acids were not detected in tissues of +A rats nor in other tissues of -A rats. These findings agree with the view that central cleavage is by far the major pathway for the formation of vitamin A from beta-carotene in healthy rats in vivo.

Topics: Animals; beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Female; Gastric Mucosa; Intestine, Small; Liver; Rats; Rats, Sprague-Dawley; Retinaldehyde; Retinoids; Vitamin A Deficiency

Retinaldehyde (RAL), a natural metabolite of beta-carotene and retinol (ROL), is tolerated by human skin after topical application.. To see if topical application of a large quantity of RAL on human skin is associated with a detectable alteration of constitutive levels of plasma retinoids resulting from metabolism of RAL in the skin.. Plasma retinoids [ROL, all-trans-retinoic acid (all-trans-RA), RAL, retinyl palmitate/oleate, 13-cis-RA and 4-oxo-13-cis-RA] were analyzed by high-pressure liquid chromatography. Determinations were done in 10 healthy male volunteers kept on a vitamin-A-poor diet before, during and after daily topical application of 7 mg of RAL to 40% of the body surface for 14 days.. The introduction of a restricted vitamin A diet before RAL application resulted in a decrease in the plasma levels of ROL, all-trans-RA and retinyl palmitate/oleate. Topical application of RAL did not induce an alteration of the plasma levels of retinoid metabolites. No RAL was detectable in any of the plasma samples.. The skin metabolism of topically applied RAL does not result in detectable alterations of constitutive levels of plasma retinoids in humans.

Topics: Administration, Topical; Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Retinaldehyde; Retinoids; Skin; Skin Absorption; Vitamin A Deficiency

A total of 6636 children, aged from 6 months to 6 years and selected throughout the country using a multi-staged stratified sample design, were examined for signs of xerophthalmia. The concentrations of retinol and of beta-carotene were measured in 742 children, including those with xerophthalmia and every twentieth of the remaining children. Anthropometric measurements were made on 2909 of the children. Bitot's spots were seen in 1.0% of all children, with a higher prevalence in the pastoral (1.6%) and cropping (1.1%) agro-ecological zones than in the zones characterized by cash crops (0.4%) and 'ensete' (false banana, Ensete ventricosum) (0.0%). One case of corneal xerosis and 2 cases of corneal scar were also seen. Serum retinol levels were in the 'deficient' range (less than 0.35 mumol l-1) in 16% and 'low' (0.35-0.69 mumol l-1) in 44% of children. Serum retinol and clinical signs did not show any correlation with occupation and education of head of household, household size or anthropometric measurements. More stunting than wasting was observed, with peak prevalence of these signs of malnutrition being observed in the second year of life.

Topics: Agriculture; Anthropometry; beta Carotene; Carotenoids; Child; Child, Preschool; Ethiopia; Female; Humans; Infant; Male; Nutrition Surveys; Ophthalmoscopy; Prevalence; Residence Characteristics; Retinaldehyde; Seroepidemiologic Studies; Vitamin A Deficiency; Xerophthalmia

Larvae of the tobacco hornworm moth Manduca sexta were reared on either a carotenoid-supplemented or a carotenoid-deficient diet. The former yields fortified adults with normal visual function, whereas visual sensitivity and rhodopsin content are reduced by 2-4 log units in the compound eyes of the deprived moths reared on the latter. We characterized the retinoids of fortified retinas and investigated the recovery of visual function in deprived moths that were provided with retinaldehyde as a source of photopigment chromophore. Retinoids were identified and measured by high-performance liquid chromatography (HPLC). Fortified retinas contained mainly 3-hydroxyretinaldehyde (R3); 11-cis R3 predominated in dark-adaptation, all-trans in light-adaptation, indicating that R3 is the photopigment chromophore. No retinoids could be measured in deprived eyes. Retinaldehyde (R1) was delivered to the retinas of deprived moths by "painting" solutions of 11-cis or all-trans R1 in dimethylsulfoxide (DMSO) on the corneal surfaces of the compound eyes or on the head capsule between the eyes. 11-cis R1 induced rapid recovery: during 3 days, sensitivity rose to within a log unit of that measured from fortified animals. By 7 days, sensitivity was close to normal. Although rhodopsin and P-face particle densities of photoreceptor membranes increased, neither rose to the levels found in fortified animals. All-trans R1 induced only a slight increase in sensitivity that could have resulted from some nonspecific isomerization of the all-trans to the 11-cis isomer; we found no evidence for a retinal isomerase that functions in darkness. Small amounts of R3 were measured in recovering retinas, indicating some conversion of R1 to R3.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Chromatography, High Pressure Liquid; Cornea; Dark Adaptation; Isomerism; Light; Moths; Photoreceptor Cells; Retina; Retinaldehyde; Retinoids; Vision, Ocular; Vitamin A Deficiency

An enzyme activity which converts retinal to retinoic acid was found in the cytosol of rat kidney. The oxidation of retinal was pH-, temperature-, time- and protein-dependent. Under the assay conditions employed, the oxidase activity had an apparent Km of 125 microM toward all-trans retinal. n-Propylgallate, butylated hydroxytoluene and quinacrine inhibited the reaction. The inhibition caused by quinacrine can be partly reversed by FAD. p-Hydroxymercuribenzoate, a sulfhydryl cross-linking agent, was a potent inhibitor. 4'-(9-Acridinylamino)methanesulfon-anisidide, an inhibitor of aldehyde oxidase, inhibited the reaction by 77% at a concentration of 3 mM. All-trans retinal reversed the inhibition caused by acetaldehyde and 2-aminobenzaldehyde. Retinol inhibited the reaction, but retinoic acid did not. The specific activity of the enzyme was increased by vitamin A deficiency. These data indicate that retinal-oxidizing enzyme activity found in the kidney is a sulfhydryl flavoprotein and its activity is dependent on the vitamin A levels of the tissues.

Topics: Animals; Cytosol; Flavin-Adenine Dinucleotide; Hydrogen-Ion Concentration; Kidney; Kinetics; Male; Oxidation-Reduction; Propyl Gallate; Quinacrine; Rats; Retinaldehyde; Retinoids; Temperature; Time Factors; Tretinoin; Vitamin A Deficiency

Rat intestinal mucosa was prepared and incubated with beta-carotene by the procedure of Goodman and Olson [Goodman, DeW. S., & Olson, J.A. (1969) Methods Enzymol. 15, 462-475] to determine beta-carotene cleavage activity. A new detection system for the reaction products of the described enzyme beta-carotene 15,15'-dioxygenase (EC 1.13.11.21) employs solvent extraction of retinoids and carotenoids followed by high-performance liquid chromatography separation and photometric detection of the pigments. It has not detected any newly formed retinal or other retinoids in the intestinal protein preparations from normal or vitamin A deficient rats. The latter were chosen as a possible source of more active enzyme preparations. With corresponding blank samples subjected to identical conditions of incubation but without added protein, small amounts of beta-apocarotenals could be detected. They were previously reported as cleavage products of beta-carotene [Ganguly, J., & Sastry, P.S. (1985) World Rev. Nutr. Diet. 45, 198-220] but are clearly not formed as a result of an enzymatic reaction. The failure to detect in vitro enzymatic central or random cleavage of the beta-carotene molecule in extracts of rat intestinal mucosa emphasizes the need to reevaluate the existing theory of conversion of beta-carotene into vitamin A.

Topics: Animals; beta Carotene; Carotenoids; Female; Intestinal Mucosa; Male; Rats; Rats, Inbred Strains; Retinaldehyde; Retinoids; Spectrophotometry; Vitamin A Deficiency

Topics: Chemical Phenomena; Chemistry; Humans; Isotretinoin; Neoplasms; Precancerous Conditions; Retinaldehyde; Skin Diseases; Tretinoin; Vitamin A; Vitamin A Deficiency

Topics: Animals; Diterpenes; Electroretinography; Male; Rats; Retina; Retinaldehyde; Rhodopsin; Vitamin A; Vitamin A Deficiency

A new, water-soluble, polymer-linked form of retinal was synthesized and tested for its ability to support the growth of vitamin A-deficient noninbred Holtzman rats and to inhibit the proliferation of melanoma cells in culture. Retinal was conjugated to the hydrazide of carboxymethyldextran in the presence of alpha-and beta-cyclodextrins. The aqueous solutions of the product contained between 200 and 1,000 micrograms retinal/ml as opposed to the low water solubility (< 0.01 micrograms/ml) of retinal itself. The retinal-dextran complex, although barely resorbed from the gastrointestinal tract, supported the growth of rats fed a vitamin A-deficient diet when administered ip at 2.3 mumol of retinal equivalent/kg body weight. Retinal and the retinal-dextran complex exhibited differential cytotoxicity toward S91 melanoma cells and caused cell lysis at 10 and 500 microM (retinal residue), respectively. At noncytotoxic doses both free retinal and its dextran-linked derivative reduced the cell proliferation rate in a time- and dose-dependent fashion with median inhibitory doses of 1 and 4 microM (retinal residue), respectively. These data demonstrated that the water-soluble retinal-dextran complex retained certain biologic activities of retinal and was less cytotoxic.

Topics: Animals; Cell Division; Cell Line; Cells, Cultured; Dextrans; Dose-Response Relationship, Drug; Male; Melanoma; Mice; Rats; Retinaldehyde; Vitamin A; Vitamin A Deficiency

Topics: Animals; Chromatography, High Pressure Liquid; Drug Stability; Rats; Retinaldehyde; Tretinoin; Vitamin A; Vitamin A Deficiency

Topics: Action Potentials; Animals; Dark Adaptation; Electroretinography; Male; Rats; Retina; Retinaldehyde; Rhodopsin; Stereoisomerism; Visual Cortex; Vitamin A; Vitamin A Deficiency

Topics: Animals; Body Weight; Hematocrit; Hemoglobins; Intestinal Absorption; Iron; Kinetics; Liver; Organ Size; Rats; Retinaldehyde; Vitamin A; Vitamin A Deficiency

A reverse phase high-pressure liquid chromatography system for rapid separation of various retinoids (vitamin A and its analogs) with little or no degradation is described. This method permits detection of as little as 22 pmol of retinoic acid. The procedure has been applied to the study of retinoic acid metabolism in vitamin A-deficient hamsters.

Topics: Animals; Chromatography, High Pressure Liquid; Cricetinae; Mesocricetus; Molecular Conformation; Retinaldehyde; Tretinoin; Vitamin A; Vitamin A Deficiency

A separation procedure for retinoids based on reversephase high-pressure liquid chromatography with solvent mixtures of acetonitrile and water is described. The method may be applied to the screening of synthetic retinoids, which have potential for use in the prevention of cancer. It is easily adapted to a variety of biological samples and can be applied to other conventional retinoid assays in liver and plasma, detecting as little as 1 nmol retinyl esters and less than 0.3 nmol retinol per g tissue. The one-step chromatography results in separation and simultaneous determination of many of the synthetic retinoids and all of the natural retinoids, including the retinyl esters that are separated into their major fatty acid components. The method has been applied to the analysis of retinoid levels in the liver and intestine of vitamin A-deficient hamsters following a p.o. dose (0.5 mg/day for 2 days) of retinyl acetate or of a synthetic vitamin A analog and is predictive of the degree to which various synthetic retinoids can be converted to retinol and stored in the liver as retinyl esters. Because of its speed, excellent recoveries, and high resolution, the method offers significant advantages over previous, more lengthy procedures.

Topics: Animals; Chromatography, High Pressure Liquid; Cricetinae; Female; Intestine, Small; Liver; Male; Mesocricetus; Retinaldehyde; Solvents; Vitamin A; Vitamin A Deficiency