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Nutrients Jan 2021Vitamin A is a fat-soluble vitamin that plays an important role in skin immunity. Deficiencies in Vitamin A have been linked to impaired immune response and increased... (Review)
Review
Vitamin A is a fat-soluble vitamin that plays an important role in skin immunity. Deficiencies in Vitamin A have been linked to impaired immune response and increased susceptibility to skin infections and inflammatory skin disease. This narrative review summarizes recent primary evidence that elucidates the role of vitamin A and its derivatives on innate immune regulators through mechanisms that promote skin immunity and sustain the skin microbiome.
Topics: Animals; Dermatitis; Humans; Immunity, Innate; Microbiota; Skin; Staphylococcus aureus; Tretinoin; Vitamin A; Vitamin A Deficiency
PubMed: 33494277
DOI: 10.3390/nu13020302 -
International Journal of Environmental... Sep 2019Rubella is a systemic virus infection that is usually mild. It can, however, cause severe birth defects known as the congenital rubella syndrome (CRS) when infection... (Review)
Review
Rubella is a systemic virus infection that is usually mild. It can, however, cause severe birth defects known as the congenital rubella syndrome (CRS) when infection occurs early in pregnancy. As many as 8%-13% of children with CRS developed autism during the rubella epidemic of the 1960s compared to the background rate of about 1 new case per 5000 children. Rubella infection and CRS are now rare in the U.S. and in Europe due to widespread vaccination. However, autism rates have risen dramatically in recent decades to about 3% of children today, with many cases appearing after a period of normal development ('regressive autism'). Evidence is reviewed here suggesting that the signs and symptoms of rubella may be due to alterations in the hepatic metabolism of vitamin A (retinoids), precipitated by the acute phase of the infection. The infection causes mild liver dysfunction and the spillage of stored vitamin A compounds into the circulation, resulting in an endogenous form of hypervitaminosis A. Given that vitamin A is a known teratogen, it is suggested that rubella infection occurring in the early weeks of pregnancy causes CRS through maternal liver dysfunction and exposure of the developing fetus to excessive vitamin A. On this view, the multiple manifestations of CRS and associated autism represent endogenous forms of hypervitaminosis A. It is further proposed that regressive autism results primarily from post-natal influences of a liver-damaging nature and exposure to excess vitamin A, inducing CRS-like features as a function of vitamin A toxicity, but without the associated dysmorphogenesis. A number of environmental factors are discussed that may plausibly be candidates for this role, and suggestions are offered for testing the model. The model also suggests a number of measures that may be effective both in reducing the risk of fetal CRS in women who acquire rubella in their first trimester and in reversing or minimizing regressive autism among children in whom the diagnosis is suspected or confirmed.
Topics: Autistic Disorder; Humans; Hypervitaminosis A; Liver; Liver Diseases; Rubella; Rubella Syndrome, Congenital; Rubella virus; Vitamin A
PubMed: 31546693
DOI: 10.3390/ijerph16193543 -
Journal of Drugs in Dermatology : JDD Jul 2022Retinoids are a mainstay of dermatologic therapy. Although prescription retinoids are more potent than over the counter retinoids, when properly formulated cosmetic... (Review)
Review
Retinoids are a mainstay of dermatologic therapy. Although prescription retinoids are more potent than over the counter retinoids, when properly formulated cosmetic retinoids offer consumers an easily accessible, reasonably priced therapeutic option. Retinol has been shown to improve fine lines and wrinkles, hyperpigmentation, skin roughness, and the appearance of photoaged skin. The efficacy and tolerability of retinol makes it preferable to prescription retinoids as many patients are intolerant of these more potent forms. In this review, we will discuss the pharmacokinetics of retinol and the clinical studies confirming its efficacy, tolerability, and safety with long-term use. J Drugs Dermatol. 2022;21:7(Suppl):s4-10.
Topics: Cosmetics; Humans; Hyperpigmentation; Retinoids; Skin; Skin Aging; Vitamin A
PubMed: 35816071
DOI: 10.36849/JDD.SO722 -
Journal of Molecular Endocrinology Nov 2022Vitamin A (retinol) is a critical micronutrient required for the control of stem cell functions, cell differentiation, and cell metabolism in many different cell types,... (Review)
Review
Vitamin A (retinol) is a critical micronutrient required for the control of stem cell functions, cell differentiation, and cell metabolism in many different cell types, both during embryogenesis and in the adult organism. However, we must obtain vitamin A from food sources. Thus, the uptake and metabolism of vitamin A by intestinal epithelial cells, the storage of vitamin A in the liver, and the metabolism of vitamin A in target cells to more biologically active metabolites, such as retinoic acid (RA) and 4-oxo-RA, must be precisely regulated. Here, I will discuss the enzymes that metabolize vitamin A to RA and the cytochrome P450 Cyp26 family of enzymes that further oxidize RA. Because much progress has been made in understanding the regulation of ALDH1a2 (RALDH2) actions in the intestine, one focus of this review is on the metabolism of vitamin A in intestinal epithelial cells and dendritic cells. Another focus is on recent data that 4-oxo-RA is a ligand required for the maintenance of hematopoietic stem cell dormancy and the important role of RARβ (RARB) in these stem cells. Despite this progress, many questions remain in this research area, which links vitamin A metabolism to nutrition, immune functions, developmental biology, and nuclear receptor pharmacology.
Topics: Cytochrome P-450 Enzyme System; Cytochrome P450 Family 26; Ligands; Micronutrients; Tretinoin; Vitamin A
PubMed: 35900851
DOI: 10.1530/JME-22-0082 -
Journal of Special Operations Medicine... 2021Vitamin A is a generic term describing compounds that have the same biological activity as retinol. Dietary vitamin A can be obtained from "provitamin A" carotenoids... (Meta-Analysis)
Meta-Analysis
Vitamin A is a generic term describing compounds that have the same biological activity as retinol. Dietary vitamin A can be obtained from "provitamin A" carotenoids (e.g., ß-carotene) found in plant foods such as carrots, cantaloupes, and sweet peppers, or as "preformed vitamin A" found in many dietary supplements, animal livers, and vitamin A-fortified foods, such as breakfast cereals, milk, cheese, and yogurt. Low consumption of vitamin A can cause night blindness, reduce immune function, and have detrimental developmental effects. Several lines of evidence suggest that excessive dietary intake of vitamin A might be associated with an increased risk of bone fractures. Meta-analysis of observational human studies that have examined vitamin A and fractures suggests that dietary consumption of large amounts of vitamin A in the form of ß-carotene likely has a protective effect, reducing the risk of fractures. On the other hand, meta-analyses that have specifically examined hip fractures have shown that total vitamin A (all types) or retinol consumption may increase the risk of hip fractures. Until more information is available, it is advisable to consume vitamin A primarily from plant sources, avoid excessive consumption from dietary supplements and animal sources, and lower consumption from fortified foods.
Topics: Animals; Carotenoids; Diet; Dietary Supplements; Fractures, Bone; Humans; Vitamin A
PubMed: 33721319
DOI: 10.55460/ETA1-NLQP -
Journal of Molecular Endocrinology Nov 2022For almost a century, vitamin A has been known as a nutrient critical for normal development, differentiation, and homeostasis; accordingly, there has been much interest... (Review)
Review
For almost a century, vitamin A has been known as a nutrient critical for normal development, differentiation, and homeostasis; accordingly, there has been much interest in understanding its mechanism of action. This review is about the discovery of specific receptors for the vitamin A derivative, retinoic acid (RA), which launched extensive molecular, genetic, and structural investigations into these new members of the nuclear receptor superfamily of transcriptional regulators. These included two families of receptors, the RAR isotypes (α, β, and γ) along with three RXR isotypes (α, β, and γ), which bind as RXR/RAR heterodimers to cis-acting response elements of RA target genes to generate a high degree of complexity. Such studies have provided deep molecular insight into how the widespread pleiotropic effects of RA can be generated.
Topics: Carrier Proteins; Receptors, Cytoplasmic and Nuclear; Receptors, Retinoic Acid; Retinoid X Receptors; Tretinoin; Vitamin A
PubMed: 36149754
DOI: 10.1530/JME-22-0097 -
Pharmacology & Therapeutics Aug 2023Vitamin A (VA, retinol) and its metabolites (commonly called retinoids) are required for the proper development of the kidney during embryogenesis, but retinoids also... (Review)
Review
Vitamin A (VA, retinol) and its metabolites (commonly called retinoids) are required for the proper development of the kidney during embryogenesis, but retinoids also play key roles in the function and repair of the kidney in adults. Kidneys filter 180-200 liters of blood per day and each kidney contains approximately 1 million nephrons, which are often referred to as the 'functional units' of the kidney. Each nephron consists of a glomerulus and a series of tubules (proximal tubule, loop of Henle, distal tubule, and collecting duct) surrounded by a network of capillaries. VA is stored in the liver and converted to active metabolites, most notably retinoic acid (RA), which acts as an agonist for the retinoic acid receptors ((RARs α, β, and γ) to regulate gene transcription. In this review we discuss some of the actions of retinoids in the kidney after injury. For example, in an ischemia-reperfusion model in mice, injury-associated loss of proximal tubule (PT) differentiation markers occurs, followed by re-expression of these differentiation markers during PT repair. Notably, healthy proximal tubules express ALDH1a2, the enzyme that metabolizes retinaldehyde to RA, but transiently lose ALDH1a2 expression after injury, while nearby myofibroblasts transiently acquire RA-producing capabilities after injury. These results indicate that RA is important for renal tubular injury repair and that compensatory mechanisms exist for the generation of endogenous RA by other cell types upon proximal tubule injury. ALDH1a2 levels also increase in podocytes, epithelial cells of the glomeruli, after injury, and RA promotes podocyte differentiation. We also review the ability of exogenous, pharmacological doses of RA and receptor selective retinoids to treat numerous kidney diseases, including kidney cancer and diabetic kidney disease, and the emerging genetic evidence for the importance of retinoids and their receptors in maintaining or restoring kidney function after injury. In general, RA has a protective effect on the kidney after various types of injuries (eg. ischemia, cytotoxic actions of chemicals, hyperglycemia related to diabetes). As more research into the actions of each of the three RARs in the kidney is carried out, a greater understanding of the actions of vitamin A is likely to lead to new insights into the pathology of kidney disorders and the development of new therapies for kidney diseases.
Topics: Vitamin A; Kidney; Retinoids; Receptors, Retinoic Acid; Tretinoin; Kidney Diseases
PubMed: 37331524
DOI: 10.1016/j.pharmthera.2023.108481 -
Autophagy Nov 2021Alzheimer disease (AD) is usually accompanied by two prominent pathological features, cerebral accumulation of amyloid-β (Aβ) plaques and presence of MAPT/tau...
Alzheimer disease (AD) is usually accompanied by two prominent pathological features, cerebral accumulation of amyloid-β (Aβ) plaques and presence of MAPT/tau neurofibrillary tangles. Dysregulated clearance of Aβ largely contributes to its accumulation and plaque formation in the brain. Macroautophagy/autophagy is a lysosomal degradative process, which plays an important role in the clearance of Aβ. Failure of autophagic clearance of Aβ is currently acknowledged as a contributing factor to increased accumulation of Aβ in AD brains. In this study, we have identified crocetin, a pharmacologically active constituent from the flower stigmas of , as a potential inducer of autophagy in AD. In the cellular model, crocetin induced autophagy in N9 microglial and primary neuron cells through STK11/LKB1 (serine/threonine kinase 11)-mediated AMP-activated protein kinase (AMPK) pathway activation. Autophagy induction by crocetin significantly increased Aβ clearance in N9 cells. Moreover, crocetin crossed the blood-brain barrier and induced autophagy in the brains' hippocampi of wild-type male C57BL/6 mice. Further studies in transgenic male 5XFAD mice, as a model of AD, revealed that one-month treatment with crocetin significantly reduced Aβ levels and neuroinflammation in the mice brains and improved memory function by inducing autophagy that was mediated by AMPK pathway activation. Our findings support further development of crocetin as a pharmacological inducer of autophagy to prevent, slow down progression, and/or treat AD. Aβ: amyloid-β; ABCB1/P-gp/P-glycoprotein: ATP-binding cassette, subfamily B (MDR/TAP), member 1; AD: Alzheimer disease; AMPK/PRKAA: AMP-activated protein kinase; APP: amyloid beta (A4) precursor protein; ATG: autophagy related; BBB: blood-brain barrier; BECN1: beclin 1, autophagy related; CAMKK2/CaMKKβ: calcium/calmodulin-dependent protein kinase kinase 2, beta; CSE: Crocus sativus extract; CTSB: cathepsin B; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; GFAP: glial fibrillary acidic protein; GSK3B/GSK3β: glycogen synthase kinase 3 beta; Kp: brain partition coefficient; LRP1: low density lipoprotein receptor-related protein 1; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MAP2: microtubule-associated protein 2; MAPK/ERK: mitogen-activated protein kinase; MAPT/tau: microtubule-associated protein tau; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; MTOR: mechanistic target of rapamycin kinase; MWM: Morris water maze; NFKB/NF-κB: nuclear factor of kappa light polypeptide gene enhancer in B cells; NMDA: N-methyl-d-aspartic acid; RPTOR: regulatory associated protein of MTOR; RPS6KB1/p70S6K: ribosomal protein S6 kinase 1; SQSTM1: sequestosome 1; SRB: sulforhodamine B; STK11/LKB1: serine/threonine kinase 11; TFEB: transcription factor EB; TSC2: TSC complex subunit 2; ULK1: unc-51 like kinase 1.
Topics: AMP-Activated Protein Kinases; Amyloid beta-Peptides; Animals; Autophagy; Carotenoids; Cell Line; Female; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Microglia; Vitamin A
PubMed: 33404280
DOI: 10.1080/15548627.2021.1872187 -
Biomedicine & Pharmacotherapy =... Aug 2023Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid....
Vitamin A (retinol) is a lipid-soluble vitamin that acts as a precursor for several bioactive compounds, such as retinaldehyde (retinal) and isomers of retinoic acid. Retinol and all-trans-retinoic acid (atRA) penetrate the blood-brain barrier and are reported to be neuroprotective in several animal models. We characterised the impact of retinol and its metabolites, all-trans-retinal (atRAL) and atRA, on ferroptosis-a programmed cell death caused by iron-dependent phospholipid peroxidation. Ferroptosis was induced by erastin, buthionine sulfoximine or RSL3 in neuronal and non-neuronal cell lines. We found that retinol, atRAL and atRA inhibited ferroptosis with a potency superior to α-tocopherol, the canonical anti-ferroptotic vitamin. In contrast, we found that antagonism of endogenous retinol with anhydroretinol sensitises ferroptosis induced in neuronal and non-neuronal cell lines. Retinol and its metabolites atRAL and atRA directly interdict lipid radicals in ferroptosis since these compounds displayed radical trapping properties in a cell-free assay. Vitamin A, therefore, complements other anti-ferroptotic vitamins, E and K; metabolites of vitamin A, or agents that alter their levels, may be potential therapeutics for diseases where ferroptosis is implicated.
Topics: Animals; Vitamin A; Ferroptosis; Lipid Peroxidation; Tretinoin; Vitamins; Retinaldehyde; Lipids
PubMed: 37236031
DOI: 10.1016/j.biopha.2023.114930 -
Nutrients Oct 2022All-trans-retinoic acid (RA), a metabolite of vitamin A (retinol), exerts profuse actions that enable multiple aspects of reproduction, embryonic development and...
All-trans-retinoic acid (RA), a metabolite of vitamin A (retinol), exerts profuse actions that enable multiple aspects of reproduction, embryonic development and post-natal regulation of energy metabolism, glucoregulatory control, organ function, and of the skeletal, immune, nervous and cardiovascular systems, as well as cell proliferation vs [...].
Topics: Pregnancy; Female; Humans; Tretinoin; Vitamin A; Autacoids
PubMed: 36364786
DOI: 10.3390/nu14214526