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International Journal of Molecular... Mar 2021Bladder cancer (BC) is the tenth most common cancer worldwide with a high recurrence rate, morbidity and mortality. Therefore, chemoprevention and improved treatment of... (Review)
Review
Bladder cancer (BC) is the tenth most common cancer worldwide with a high recurrence rate, morbidity and mortality. Therefore, chemoprevention and improved treatment of BC are of paramount importance. Epidemiological studies suggest that adequate vitamin A intake may be associated with reduced BC risk. In addition, retinoids, natural and synthetic derivatives of vitamin A, are intensively studied in cancer research due to their antioxidant properties and their ability to regulate cell growth, differentiation, and apoptosis. Findings from in vivo and in vitro models of BC show great potential for the use of retinoids in the chemoprevention and treatment of BC. However, translation to the clinical practice is limited. In this narrative review we discuss: (i) vitamin A and retinoid metabolism and retinoic acid signalling, (ii) the pathobiology of BC and the need for chemoprevention, (iii) the epidemiological evidence for the role of dietary vitamin A in BC, (iv) mechanistic insights obtained from in vivo and in vitro models, (v) clinical trials of retinoids and the limitations of retinoid use, (vi) novel systems of retinoid delivery, and (vii) components of retinoid signalling pathways as potential novel therapeutic targets.
Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; Apoptosis; Cell Differentiation; Humans; Retinoids; Signal Transduction; Urinary Bladder Neoplasms; Vitamin A
PubMed: 33805295
DOI: 10.3390/ijms22073510 -
Molecular Metabolism Oct 2020Extrahepatic vitamin A is housed within organ-specific stellate cells that support local tissue function. These cells have been reported in the vocal fold mucosa (VFM)...
OBJECTIVE
Extrahepatic vitamin A is housed within organ-specific stellate cells that support local tissue function. These cells have been reported in the vocal fold mucosa (VFM) of the larynx; however, it is unknown how vitamin A reaches and is disseminated among VFM target cells, how VFM storage and utilization vary as a function of total body stores, and how these parameters change in the context of pathology. Therefore, in this study, we investigated fundamental VFM vitamin A uptake and metabolism.
METHODS
Using cadaveric tissue and serum from human donors representing the full continuum of clinical vitamin A status, we established a concentration range and analyzed the impact of biologic and clinical covariates on VFM vitamin A. We additionally conducted immunodetection of vitamin A-associated markers and pharmacokinetic profiling of orally dosed α-retinyl ester (a chylomicron tracer) in rats.
RESULTS
Serum vitamin A was a significant predictor of human VFM concentrations, suggesting that VFM stores may be rapidly metabolized in situ and replenished from the circulatory pool. On a vitamin A-sufficient background, dosed α-vitamin A was detected in rat VFM in both ester and alcohol forms, showing that, in addition to plasma retinol and local stellate cell stores, VFM can access and process postprandial retinyl esters from circulating chylomicra. Both α forms were rapidly depleted, confirming the high metabolic demand for vitamin A within VFM.
CONCLUSION
This thorough physiological analysis validates VFM as an extrahepatic vitamin A repository and characterizes its unique uptake, storage, and utilization phenotype.
Topics: Aged; Aged, 80 and over; Animals; Female; Hepatic Stellate Cells; Humans; Liver; Male; Middle Aged; Mucous Membrane; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Vitamin A; Vocal Cords
PubMed: 32473404
DOI: 10.1016/j.molmet.2020.101025 -
Leukemia Aug 2023Vitamin C has been demonstrated to regulate hematopoietic stem cell frequencies and leukemogenesis by augmenting and restoring Ten-Eleven Translocation-2 (TET2)...
Vitamin C has been demonstrated to regulate hematopoietic stem cell frequencies and leukemogenesis by augmenting and restoring Ten-Eleven Translocation-2 (TET2) function, potentially acting as a promising adjunctive therapeutic agent for leukemia. However, glucose transporter 3 (GLUT3) deficiency in acute myeloid leukemia (AML) impedes vitamin C uptake and abolishes the clinical benefit of vitamin C. In this study, we aimed to investigate the therapeutic value of GLUT3 restoration in AML. In vitro GLUT3 restoration was conducted with the transduction of GLUT3-overexpressing lentivirus or the pharmacological salvage with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) treatment to OCI-AML3, a naturally GLUT3-deficient AML cell line. The effects of GLUT3 salvage were further confirmed in patient-derived primary AML cells. Upregulation of GLUT3 expression made AML cells successfully augment TET2 activity and enhanced the vitamin C-induced anti-leukemic effect. Pharmacological GLUT3 salvage has the potential to overcome GLUT3 deficiency in AML and improves the antileukemic effect of vitamin C treatments.
Topics: Humans; Ascorbic Acid; Glucose Transporter Type 3; Leukemia, Myeloid, Acute; Vitamin A; Translocation, Genetic; DNA-Binding Proteins; Dioxygenases
PubMed: 37393342
DOI: 10.1038/s41375-023-01954-5 -
International Journal of Obesity (2005) Mar 2021Early consumption of obesogenic diets, rich in saturated fat and added sugar, is associated with a plethora of biological dysfunctions, at both peripheral and brain...
BACKGROUND
Early consumption of obesogenic diets, rich in saturated fat and added sugar, is associated with a plethora of biological dysfunctions, at both peripheral and brain levels. Obesity is also linked to decreased vitamin A bioavailability, an essential molecule for brain plasticity and memory function.
METHODS
Here we investigated in mice whether dietary vitamin A supplementation (VAS) could prevent some of the metabolic, microbiota, neuronal and cognitive alterations induced by obesogenic, high-fat and high-sugar diet (HFSD) exposure from weaning to adulthood, i.e. covering periadolescent period.
RESULTS
As expected, VAS was effective in enhancing peripheral vitamin A levels as well as hippocampal retinoic acid levels, the active metabolite of vitamin A, regardless of the diet. VAS attenuated HFSD-induced excessive weight gain, without affecting metabolic changes, and prevented alterations of gut microbiota α-diversity. In HFSD-fed mice, VAS prevented recognition memory deficits but had no effect on aversive memory enhancement. Interestingly, VAS alleviated both HFSD-induced higher neuronal activation and lower glucocorticoid receptor phosphorylation in the hippocampus after training.
CONCLUSION
Dietary VAS was protective against the deleterious effects of early obesogenic diet consumption on hippocampal function, possibly through modulation of the gut-brain axis.
Topics: Animals; Brain-Gut Axis; Cognition; Diet, High-Fat; Dietary Supplements; Gastrointestinal Microbiome; Hippocampus; Male; Memory; Mice; Mice, Inbred C57BL; Vitamin A
PubMed: 33223517
DOI: 10.1038/s41366-020-00723-z -
International Journal For Vitamin and... Jun 2023Our objective was to study the effect of differing dietary crude protein and vitamin A on retinoid metabolism in a periparturient rat model. Sixty female rats,...
Our objective was to study the effect of differing dietary crude protein and vitamin A on retinoid metabolism in a periparturient rat model. Sixty female rats, approximately 21 d before parturition, were fed rations containing either low protein (13%; LP) or high protein (22%; HP) crude protein and either low vitamin A (3 IU/g; LA) or high vitamin A (5 IU/g; HA), yielding treatments HPHA, HPLA, LPHA, and LPLA. Samples were collected at d -14, d +3, and +10 relative to parturition and analyzed for retinoid acid (RA), RA, and retinol. At d -14, serum RA concentrations decreased compared to baseline. At both d +3 and d +10, serum retinol increased and liver RA decreased. In the small intestine, 13-cis RA was higher in HPHA than HPLA pre-partum (0.93±0.12 vs. 0.40±0.12 ng/ml, =0.04). Post-partum, RA was lower in high vitamin HPHA and LPHA groups (0.35±0.06 and 0.38±0.06 ng/ml) than in low vitamin A HPLA and LPLA treatments (0.50±0.06 and 1.32±0.06 ng/ml, <0.01). In rats fed LA diets, TNF-alpha expression tended to be lower in HPLA than LPLA groups on day +3 (0.69±0.34 vs 1.00±0.52, =0.08), but not day +10 (0.56±0.25 vs. 1.00±0.49 fold change, >0.10). Retinoids accumulated during pregnancy and were mobilized during lactation. The sequestration of retinoids was increased when dietary protein content was low. Further studies are needed to investigate how retinoid metabolism could be manipulated to improve vitamin A delivery to milk.
Topics: Pregnancy; Rats; Female; Animals; Vitamin A; Milk; Retinoids; Diet; Lactation; Dietary Proteins
PubMed: 34013777
DOI: 10.1024/0300-9831/a000712 -
Critical Reviews in Food Science and... Nov 2023Abnormal fetal growth increases risks of childhood health complications. Vitamin A supplementation (VAS) is highly accessible, but literature inconsistency regarding... (Meta-Analysis)
Meta-Analysis
Abnormal fetal growth increases risks of childhood health complications. Vitamin A supplementation (VAS) is highly accessible, but literature inconsistency regarding effects of maternal VAS on fetal and childhood growth outcomes exists, deterring pregnant women from VAS during pregnancy. This meta-analysis aimed to analyze effects of vitamin A only or vitamin A + co-intervention during pregnancy in healthy mothers (MH) or with complications (MC, night blindness and HIV positive) on perinatal growth outcomes, also assess VAS dose impacts. The Cochrane Library, PubMed, ScienceDirect, Scopus, Embase and Web of Science databases were searched from inception to July 15, 2021. We covered subgroup analyses, including VAS in MH or MC within randomized controlled trial (RCT) or observational studies (OS). Fifty-five studies were included in this meta-analysis (426,098 pregnancies). Vitamin A decreased risk of preterm birth by 9% in MH-RCT ( < 0.001), by 62% in MH-OS ( = 0.029), by 10% in MC-RCT ( = 0.089); decreased LBW by 24% in MC-RCT ( = 0.032); increased neonatal weight in MC-RCT (SMD 0.96; = 0.051). Besides, vitamin A + co-intervention decreased risks of preterm by 18% in MH-OS ( = 0.021); LBW by 25% in MH-OS ( < 0.001); by 32% in MC-RCT ( = 0.006); decreased neonatal defects by 33% in MH-OS ( = 0.064); decreased anemia by 25% in MH-OS ( = 0.0003); increased neonatal weight in MH-OS (SMD 0.51; = 0.014); and increased neonatal length in MH-OS (SMD 1.83; = 0.013). Meta-regression of VAS dose with individual outcomes was not significant, and no side effects were observed for VAS doses up to 4000 mcg (RAE/d). Regardless of maternal health conditions, VAS during pregnancy can safely and effectively improve fetal development and neonatal health even in mothers without VAD.
Topics: Pregnancy; Infant, Newborn; Female; Child; Humans; Vitamin A; Pregnancy Complications; Dietary Supplements; Premature Birth; Pregnancy Outcome
PubMed: 35852163
DOI: 10.1080/10408398.2022.2099810 -
Acta Scientiarum Polonorum. Technologia... 2017Routine administration of vitamin A, recommended in CF patients, can help to prevent its deficiency. However, high vitamin A supplementation may lead to its excessive...
BACKGROUND
Routine administration of vitamin A, recommended in CF patients, can help to prevent its deficiency. However, high vitamin A supplementation may lead to its excessive level and possible toxicity. Therefore, the aim of the present study was to assess the status of vitamin A and the determinants of its body resources in CF patients.
METHODS
In 196 CF patients aged from 4 months to 47 years, the following parameters were analysed: nutritional status (standardized body weight and height, serum albumin concentration) and clinical expression of disease (lung function - spirometry; biochemical markers of liver function - ALT, AST, GGT; respiratory tract colonization by Pseudomonas aeruginosa; diabetes; cirrhosis, non-cirrhotic liver disease; exocrine pancreatic function - fecal elastase-1 concentration; blood clotting - INR and vitamin A supplementation).
RESULTS
Median vitamin A concentration in the study group was 383.0 ng/ml (1st-3rd quartile: 316.5-457.0). Vitamin A deficiency was found in 32 (16.3%) subjects studied. Vitamin A concentrations above the reference range were observed only in 3 (1.5%) CF patients. CF patients with vitamin A deficiency were significantly older and had lower values of FEV1 compared to CF subjects with normal vitamin A status. Moreover, vitamin A deficiency occurred more frequently in CF patients with diabetes, Pseudomonas aeruginosa colo- nization, worse lung function and in those without vitamin A supplementation. However, in multiple linear regression analyses, none of the independent variables was documented to be important for predicting vita- min A status.
CONCLUSIONS
Vitamin A body resources in CF patients are mostly normal. Moreover, there are no good de- terminants of vitamin A status in these patients. Further studies targeted at exploring potential toxicity and deficiencies of vitamin A in CF patients are needed.
Topics: Adolescent; Adult; Child; Child, Preschool; Cystic Fibrosis; Female; Humans; Infant; Male; Middle Aged; Nutritional Status; Risk Factors; Vitamin A; Vitamin A Deficiency; Young Adult
PubMed: 29055982
DOI: 10.17306/J.AFS.0473 -
Eastern Mediterranean Health Journal =... Sep 2022Incomplete data are often presented for determining the role of vitamin A supplement therapy for improving treatment outcomes in patients with COVID-19. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Incomplete data are often presented for determining the role of vitamin A supplement therapy for improving treatment outcomes in patients with COVID-19.
AIMS
We compared treatment effects between a group that received vitamin A added to the standard COVID-19 treatment and another group that received the standard drug treatment alone.
METHODS
Participants in this triple-blind controlled trial comprised 182 COVID-19 outpatients in Saveh City, Markazi Province, Islamic Republic of Iran, in 2020. Patients were randomly divided into experimental (n = 91) and control (n = 91) groups. Patients in the control group received the national standard treatment for COVID-19 (hydroxychloroquine), and those in the intervention group received 25 000 IU/d oral vitamin A for 10 days in addition to the standard treatment recommended by the national protocol. We evaluated the clinical symptoms, paraclinical criteria, and hospitalization status before and after 10 days of interventions.
RESULTS
The treatment groups did not differ significantly in clinical and paraclinical symptoms before the intervention. However, clinical symptoms such as fever, body ache, weakness and fatigue, paraclinical symptoms, white blood cell count, and C-reactive protein showed significantly greater decreases in the experimental group 10 days post-intervention compared with the standard treatment alone (P < 0.05).
CONCLUSION
Vitamin A supplementation demonstrated efficacy in improving some clinical and paraclinical symptoms in patients with COVID-19. Future studies should evaluate vitamin A supplementation with a larger sample size and compare different dosages, especially in hospitalized patients.
Topics: C-Reactive Protein; Dietary Supplements; Humans; Hydroxychloroquine; SARS-CoV-2; Treatment Outcome; Vitamin A; COVID-19 Drug Treatment
PubMed: 36205206
DOI: 10.26719/emhj.22.064 -
Current Drug Targets 2015The liver is essential for the control of glucose and lipid metabolism. Excessive accumulation of fat in the liver disturbs its function and leads to the development of... (Review)
Review
The liver is essential for the control of glucose and lipid metabolism. Excessive accumulation of fat in the liver disturbs its function and leads to the development of fatty liver diseases. The nonalcoholic fatty liver disease (NAFLD) is a common type of fatty liver disease found in patients who have not consumed significant amount of alcohol. Multiple factors and cell types contribute to the development and progression of NAFLD. Diets contain macronutrients with energy and micronutrients with regulatory roles. As an essential micronutrient, vitamin A (VA), plays critical roles in various physiological functions including the regulation of glucose and lipid homeostasis in the liver. The body's VA is mainly stored in quiescent hepatic stellate cells (HSCs) in the liver. Hepatocytes actively metabolize VA, and change glucose and lipid metabolism in response to VA metabolites. Interestingly, the activated HSCs lose their VA content and contribute to the NAFLD progression. Significant number of studies have been conducted to investigate the link between VA metabolism and NAFLD development. This review is to summarize current literatures that discuss the changes of VA metabolism occurring locally between hepatocytes and HSCs, and intracellularly in hepatocytes during the course of NAFLD development. It appears that factors derived from HSCs and hepatocytes mutually affect each other, which contributes to NAFLD development. Additionally, this review discusses the potential mechanism by which excessive VA metabolism increases lipogenesis and contributes to fat accumulation in hepatocytes. It offers potential future directions for the study of the role of VA metabolism in the NAFLD development.
Topics: Gene Expression Regulation; Glucose; Humans; Lipid Metabolism; Liver; Non-alcoholic Fatty Liver Disease; Triglycerides; Vitamin A
PubMed: 25808650
DOI: 10.2174/1389450116666150325231015 -
Pakistan Journal of Biological Sciences... Jan 2021<b>Background and Objective:</b> Vitamin A Deficiency (VAD) is a critical public health problem that affects the health of kids worldwide and may induce...
<b>Background and Objective:</b> Vitamin A Deficiency (VAD) is a critical public health problem that affects the health of kids worldwide and may induce anemia and oxidative stress. The current study aimed to pre-clinically assess the effect of a cupcake, prepared to be served for primary school children, on vitamin A deficiency and related anemia and oxidative stress in rats. <b>Materials and Methods:</b> Flour of flash orange sweet potatoes, as a rich source of pro-vitamin A, was used to prepare the cupcake. The chemical composition, amino acids and sensory evaluation of the cupcake were done. The biological evaluation was carried out using 18 weaning rats in three groups (control group, vitamin A-deficient group and vitamin A-deficient group fed on a diet fortified with 20% of the prepared cupcake for two months). <b>Results:</b> The results indicated the high value of vitamin A in the prepared cupcake. Excellent sensory characteristics were noticed. Feeding on the VDA diet fortified with the prepared cupcake suppressed the reduction in Retinol-Binding Protein (RBP), hemoglobin and iron. Total Iron Binding Capacity (TIBC) increased in the VAD group. Also, feeding on the prepared cupcake suppressed the reduction in Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) and the elevation of Malondialdehyde (MDA). <b>Conclusion:</b> It can be suggested that the prepared cupcake is promising in preventing of vitamin A deficiency and related anemia and oxidative stress. Thus, the prepared cupcake may be efficient for children to prevent vitamin A deficiency.
Topics: Analysis of Variance; Anemia; Animals; Dietary Supplements; Disease Models, Animal; Hemoglobins; Oxidative Stress; Rats; Rats, Wistar; Vitamin A; Vitamin A Deficiency
PubMed: 34486322
DOI: 10.3923/pjbs.2021.366.373