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Frontiers in Immunology 2020Tissue resident intestinal macrophages are known to exhibit an anti-inflammatory phenotype and produce little pro-inflammatory cytokines upon TLR ligation, allowing...
Tissue resident intestinal macrophages are known to exhibit an anti-inflammatory phenotype and produce little pro-inflammatory cytokines upon TLR ligation, allowing symbiotic co-existence with the intestinal microbiota. However, upon acute events such as epithelial damage and concomitant influx of microbes, these macrophages must be able to quickly mount a pro-inflammatory response while more inflammatory macrophages are recruited from the blood stream simultaneously. Here, we show that dietary intake of vitamin A is required for the maintenance of the anti-inflammatory state of tissue resident intestinal macrophages. Interestingly, these anti-inflammatory macrophages were characterized by high levels of Dectin-1 expression. We show that Dectin-1 expression is enhanced by the vitamin A metabolite retinoic acid and our data suggests that Dectin-1 triggering might provide a switch to induce a rapid production of pro-inflammatory cytokines. In addition, Dectin-1 stimulation resulted in an altered metabolic profile which is linked to a pro-inflammatory response. Together, our data suggests that presence of vitamin A in the small intestine enhances an anti-inflammatory phenotype as well as Dectin-1 expression by macrophages and that this anti-inflammatory phenotype can rapidly convert toward a pro-inflammatory state upon Dectin-1 signaling.
Topics: Animals; Inflammation; Intestines; Lectins, C-Type; Macrophages; Mice, Inbred C57BL; Signal Transduction; Tretinoin; Vitamin A
PubMed: 32296441
DOI: 10.3389/fimmu.2020.00551 -
Nutrients Jun 2023Dietary deficiencies in zinc (Zn) and vitamin A (VA) are among the leading micronutrient deficiencies globally and previous research has proposed a notable interaction...
Dietary deficiencies in zinc (Zn) and vitamin A (VA) are among the leading micronutrient deficiencies globally and previous research has proposed a notable interaction between Zn and VA physiological status. This study aimed to assess the effects of zinc and vitamin A (isolated and combined) on intestinal functionality and morphology, and the gut microbiome (). The study included nine treatment groups (~11)-no-injection (NI); HO; 0.5% oil; normal zinc (40 mg/kg ZnSO) (ZN); low zinc (20 mg/kg) (ZL); normal retinoid (1500 IU/kg retinyl palmitate) (RN); low retinoid (100 IU/kg) (RL); normal zinc and retinoid (40 mg/kg; 1500 IU/kg) (ZNRN); low zinc and retinoid (ZLRL) (20 mg/kg; 100 IU/kg). Samples were injected into the amniotic fluid of the fertile broiler eggs. Tissue samples were collected upon hatch to target biomarkers. ZLRL reduced ZIP4 gene expression and upregulated ZnT1 gene expression ( < 0.05). Duodenal surface area increased the greatest in RL compared to RN ( < 0.01), and ZLRL compared to ZNRN ( < 0.05). All nutrient treatments yielded shorter crypt depths ( < 0.01). Compared to the oil control, ZLRL and ZNRN reduced ( < 0.05) the cecal abundance of and genera ( < 0.05). These results suggest a potentially improved intestinal epithelium proceeding with Zn and VA intra-amniotic administration. Intestinal functionality and gut bacteria were modulated. Further research should characterize long-term responses and the microbiome profile.
Topics: Animals; Chickens; Zinc; Vitamin A; Intestinal Mucosa; Gastrointestinal Microbiome
PubMed: 37375657
DOI: 10.3390/nu15122754 -
Methods in Enzymology 2020Vitamin A (retinol) is an essential nutrient for embryonic development and adult homeostasis. Signaling by vitamin A is carried out by its active metabolite, retinoic...
Vitamin A (retinol) is an essential nutrient for embryonic development and adult homeostasis. Signaling by vitamin A is carried out by its active metabolite, retinoic acid (RA), following a two-step conversion. RA is a small, lipophilic molecule that can diffuse from its site of synthesis to neighboring RA-responsive cells where it binds retinoic acid receptors within RA response elements of target genes. It is critical that both vitamin A and RA are maintained within a tight physiological range to protect against developmental disorders and disease. Therefore, a series of compensatory mechanisms exist to ensure appropriate levels of each. This strict regulation is provided by a number synthesizing and metabolizing enzymes that facilitate the precise spatiotemporal control of vitamin A metabolism, and RA synthesis and signaling. In this chapter we describe protocols that (1) biochemically isolate and quantify vitamin A and its metabolites and (2) visualize the spatiotemporal activity of genes and proteins involved in the signaling pathway.
Topics: Embryonic Development; Female; Humans; Pregnancy; Receptors, Retinoic Acid; Signal Transduction; Tretinoin; Vitamin A
PubMed: 32359653
DOI: 10.1016/bs.mie.2020.03.011 -
Food and Nutrition Bulletin Jun 2016Retinol isotope dilution (RID) methodology provides a quantitative estimate of total body vitamin A (VA) stores and is the best method currently available for assessing... (Review)
Review
BACKGROUND
Retinol isotope dilution (RID) methodology provides a quantitative estimate of total body vitamin A (VA) stores and is the best method currently available for assessing VA status in adults and children. The methodology has also been used to test the efficacy of VA interventions in a number of low-income countries. Infections, micronutrient deficiencies (eg, iron and zinc), liver disease, physiological age, pregnancy, and lactation are known or hypothesized to influence the accuracy of estimating total body VA stores using the isotope dilution technique.
OBJECTIVE
Our objectives were to review the strengths and limitations of RID methods, to discuss what is known about the impact of various factors on results, and to summarize contributions of model-based compartmental analysis to assessing VA status.
METHODS
Relevant published literature is reviewed and discussed.
RESULTS
Various equations and compartmental modeling have been used to estimate the total body VA stores using stable isotopes, including a newer 3-day equation that provides an estimate of total body VA stores in healthy adults. At present, there is insufficient information on absorption of the isotope tracer, and there is a need to further investigate how various factors impact the application of RID techniques in field studies.
CONCLUSIONS
Isotope dilution methodology can provide useful estimates of total body VA stores in apparently healthy populations under controlled study conditions. However, more research is needed to determine whether the method is suitable for use in settings where there is a high prevalence of infection, iron deficiency, and/or liver disease.
Topics: Child, Preschool; Confounding Factors, Epidemiologic; Dose-Response Relationship, Drug; Female; Humans; Indicator Dilution Techniques; Infant; Infant, Newborn; Isotope Labeling; Models, Theoretical; Pregnancy; Vitamin A; Vitamin A Deficiency
PubMed: 27053491
DOI: 10.1177/0379572116630642 -
ACS Applied Bio Materials Mar 2022Vitamin A is a fat-soluble compound widely known for vision health. Highly variable reports on its effects on bone health have necessitated further research to truly...
Vitamin A is a fat-soluble compound widely known for vision health. Highly variable reports on its effects on bone health have necessitated further research to truly understand its role on bone cell proliferation. Retinol, one bioactive form of vitamin A, is incorporated into synthetic bone graft scaffolds for low load-bearing clinical bone treatment. The objective of this work is to understand the effects of retinol on osteoblast and osteoclast cells when embedded within calcium phosphate matrices, including interconnected porous 3D printed tricalcium phosphate scaffolds. Results show that hydrophobic retinol can be released from bone scaffolds when a combination of biodegradable polymers, polycaprolactone and polyethylene glycol, are employed as drug carriers. The release of retinol can support a 20 ± 1% increase in osteoblast (bone-forming) cell proliferation with proper cell adhesion and filopodial extensions. Osteoclast cell morphology is necrosed and torn with a reduction in proliferation at approximately 6 ± 1% when retinol is present. In addition, inhibition of osteoclastic resorption pit bays is noted using scanning electron microscopy. With the scaffolds' round pore interconnectivity facilitating retinol release, this system can provide an alternative to traditional bone grafts while additionally supporting bone healing through enhanced osteoblast cell proliferation and inhibition of osteoclast resorption activity.
Topics: Calcium Phosphates; Cell Proliferation; Porosity; Printing, Three-Dimensional; Tissue Scaffolds; Vitamin A
PubMed: 35258918
DOI: 10.1021/acsabm.1c01181 -
Biomedicine & Pharmacotherapy =... Jan 2019Cancer development has been directly related to oxidative stress. During chemotherapy, some cancer patients use dietary antioxidants to avoid nutritional deficiencies... (Review)
Review
Cancer development has been directly related to oxidative stress. During chemotherapy, some cancer patients use dietary antioxidants to avoid nutritional deficiencies due to cancer treatment. Among the antioxidants consumed, there are vitamins, including retinyl palmitate (PR) and ascorbic acid (AA), which have the capacity to reduce free radicals formation, protect cellular structures and maintain the cellular homeostasis. This systematic review evaluated the antioxidant and antitumor mechanisms of retinol palmitate (a derivative of vitamin A) and/or ascorbic acid (vitamin C) in cancer-related studies. Ninety-seven (97) indexed articles in the databases PubMed and Science Direct, published between 2013 and 2017, including 23 clinical studies (5 for every single compound while 13 in interaction) and 74 non-clinical studies (37 for retinol palmitate, 36 for ascorbic acid and 1 in interaction) were considered. Antioxidant and antitumor effects, with controversies over dosage and route of administration, were observed for the test compounds in their isolated form or associated in clinical studies. Prevention of cancer risks against oxidative damage was seen in lower doses of retinol palmitate and/or vitamin C. However, at high doses, they can generate reactive oxygen species, cytotoxicity and apoptosis in test systems. Non-clinical studies using cell lines have allowed understanding the mechanisms related to antioxidants and antitumor effects of the isolated compounds, however, studies on vitamin interactions, acting as antioxidants and/or antitumor are still rare and controversial. More studies, mainly related to modulation of antineoplastic drugs are needed for understanding the risks and benefits of their use during treatment in order to achieve effectiveness in cancer therapy and patient's quality of life.
Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Diterpenes; Humans; Reactive Oxygen Species; Retinyl Esters; Vitamin A
PubMed: 30551390
DOI: 10.1016/j.biopha.2018.10.115 -
The Journal of Nutrition Mar 2015A critical role for vitamin A (VA) in development is well established, but still relatively little is known about whole-body VA metabolism in early postnatal life.... (Review)
Review
A critical role for vitamin A (VA) in development is well established, but still relatively little is known about whole-body VA metabolism in early postnatal life. Recently, methods of mathematical modeling have begun to shed light on retinol kinetics in the postnatal growth period and on the effect of retinoid supplementation on retinol kinetics. Comparison of kinetic parameters from tracer studies in neonatal rats with those previously determined in models of VA metabolism in the adult suggests both similarities and differences in the relative transfer rates of plasma retinol to extrahepatic tissues, resulting in similarities and differences in kinetic parameters and inferences about physiologic processes. Similarities between neonatal and adult models include the capacity for efficient digestion and absorption of VA; characteristics of a high-response system; extensive retinol recycling among liver, plasma, and extrahepatic tissues; and comparable VA disposal rates. Differences between neonatal and adult models include that, in neonates, retinol turnover is faster and retinol recycling is much more extensive; there is a greater role for extrahepatic tissues in the uptake of chylomicron VA; and the intestine plays an important role in chylomicron VA uptake, especially in neonatal rats treated with a supplement containing VA. In summary, retinol kinetic modeling in the neonatal rat has provided a first view of whole-body VA metabolism in this age group and suggests that VA kinetics in neonatal rats differs in many ways from that in adults, perhaps reflecting an adaption to the lower VA concentration found in neonates compared with adults.
Topics: Age Factors; Animals; Animals, Newborn; Biological Transport; Chylomicrons; Models, Biological; Rats; Vitamin A
PubMed: 25540407
DOI: 10.3945/jn.114.204065 -
European Journal of Pharmaceutical... Jul 2022Targeting hepatic stellate cells (HSCs) can improve the therapeutic efficacy of medicines used to treat hepatic fibrosis. The present work aimed to study the feasibility...
Targeting hepatic stellate cells (HSCs) can improve the therapeutic efficacy of medicines used to treat hepatic fibrosis. The present work aimed to study the feasibility of homing devices with vitamin A(V) chemically attached for delivering betulin(Bt)specifically to HSCs. The manufacture and characterisation of V modified poly (ethylene glycol) -poly (lactide-co-glycolide) block copolymer micelles loaded with Bt (Bt/ VPPMs) and their potential therapeutic benefits in vitro and in vivo are described in this paper. Bt/VPPMs were made in a nearly spherical core-shell configuration with diameters under 200nm.In vitro release study showed that Bt/VPPMs exhibited steady and continuous release for over 168 hours. Bt/VPPMs had good biocompatibility at the cellular level, according to the safety evaluation, and elicited no inflammatory response in mice. More importantly, as uptake behavior studied in cells and bioimaging experiments in vivo, Bt/VPPMs exhibited an instinctive liver- targeting capability to focus on activated HSCs. Efficacy tests revealed that administering Bt/VPPMs effectively inhibits collagen I expression in LX-2 cells in vitro, and this effect was also seen in a mouse model of liver fibrosis. Overall, results demonstrated that Bt/VPPMs is a promising drug delivery system that possesses specific HSCs targeting ability for treating hepatic fibrosis.
Topics: Animals; Hepatic Stellate Cells; Liver Cirrhosis; Mice; Micelles; Polymers; Triterpenes; Vitamin A
PubMed: 35429602
DOI: 10.1016/j.ejps.2022.106189 -
Asia Pacific Journal of Clinical... 2003There is general consensus that food-based approaches are viable and sustainable options for addressing vitamin A deficiency in populations. One such example is the... (Review)
Review
There is general consensus that food-based approaches are viable and sustainable options for addressing vitamin A deficiency in populations. One such example is the fortification of food which, if properly monitored, could make a significant contribution towards improving the vitamin A status of populations throughout the world. Red palm fruit oil (RPO) with its high content of natural carotenoids, lends itself exceptionally well to this purpose at both household and commercial level. Results are now available from several feeding trials incorporating RPO into diets at household level or into commercially manufactured products. RPO in the maternal diet was shown to improve the vitamin A status of lactating mothers and their infants. Consumption of RPO incorporated in a sweet snack or biscuits significantly improved plasma retinol concentrations in children with subclinical vitamin A deficiency. There is evidence that if only 35-50% of the recommended daily intake for vitamin A were to be provided by RPO, it may be sufficient to prevent vitamin A deficiency (hypovitaminosis A). Red palm oil has a highly bioconvertible form of alpha- and beta-carotene, a long shelf life, and a higher cost/benefit ratio when compared to other approaches such as high-dose-vitamin A supplements and fortification of foods with retinyl ester fortificants. Consumption of RPO is safe and cannot produce hypervitaminosis A. Considering all the current information about RPO, the initiation of food-based interventions involving its use in developing countries with an endemic vitamin A deficiency problem, appears to be a logical choice.
Topics: Biological Availability; Food, Fortified; Humans; Palm Oil; Plant Oils; Vitamin A; Vitamin A Deficiency
PubMed: 14506003
DOI: No ID Found -
British Medical Journal Mar 1952
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Vitamin A
PubMed: 14904976
DOI: No ID Found