Vitamin A Deficiency Group Research Articles

A new insight into the immune regulatory functions of vitamin A in children and adolescents

Background/Aim Vitamin A deficiency (VAD) is a serious and widespread public health problem. Vitamin A has an important role in regulating human immune function. It increases rates and severity of infections in young children mainly in developing countries. The present study aims to assess the effect of vitamin A on cluster of differentiation 4 (CD4) and thymosin β4 (Tβ4) levels as indicators of adaptive immunity. Moreover, we evaluate the association between serum vitamin A concentration and BMI among Egyptian children and adolescents.Patients and methods This cross-sectional survey was conducted on 46 apparently healthy participants, including 19 girls and 27 boys aged from 3 to 17 years. We assessed weight and height using standard techniques. Serum vitamin A, CD4, and Tβ4 concentrations were assessed by using enzyme-linked immunosorbent assay kits. We planned to divide the participants into vitamin A-sufficient and vitamin A-deficient groups according to its level.Results Cutoff for VAD was 44 μg/dl. It was detected in 56.6% of the enrolled participants. Vitamin A was significantly lower in teenagers comparative with children (P=0.04). Vitamin A and Tβ4 levels were significantly decreased in deficient group in comparison with sufficient one at P values of 0.002 and 0.017, respectively, whereas CD4 level was nonsignificantly decreased in vitamin A-deficient patients compared with the sufficient ones. A significant positive correlation was detected between vitamin A and both of CD4 (r=0.348, P=0.018) and Tβ4 (r=0.392, P=0.007). A significant positive correlation was found between vitamin A and BMI (r=0.311, P=0.035).Conclusion Vitamin A may influence Tβ4 and CD4 levels. This study is the first to explore the effect of vitamin A on Tβ4 level in children and adolescents and correlate it with CD4 level. This finding must be verified using large-scale studies.

Classification of vitamin A deficiency levels by ocular changes in Japanese black cattle

To help Japanese black cattle farmers diagnose vitamin A deficiency (VAD) levels in cattle, eye images of 40 cattle were recorded monthly during their vitamin A manipulated period using a 2-CCD camera. Ocular features extracted from images, including pupil colour, pupillary light reflex and light reflection, were investigated. Multivariate classification methods (SIMCA and PLS-DA) were used to classify cattle into mild, moderate and severe VAD groups. Five variables (r, I, CA, IPR, I_RFL) were used for classification. The mild and severe VAD groups could be classified with over 85% correct classification rate. However, the moderate VAD group could not be discriminated adequately. A VAD index was developed and proven to be effective in representing VAD status. The results showed the potential for ocular changes to be utilised as an aid to farm management.

Vitamin A supplementation in early life enhances the intestinal immune response of rats with gestational vitamin A deficiency by increasing the number of immune cells.

Vitamin A is a critical micronutrient for regulating immunity in many organisms. Our previous study demonstrated that gestational or early-life vitamin A deficiency decreases the number of immune cells in offspring. The present study aims to test whether vitamin A supplementation can restore lymphocyte pools in vitamin A-deficient rats and thereby improve the function of their intestinal mucosa; furthermore, the study aimed to identify the best time frame for vitamin A supplementation. Vitamin A-deficient pregnant rats or their offspring were administered a low-dose of vitamin A daily for 7 days starting on gestational day 14 or postnatal day 1, day 14 or day 28. Serum retinol concentrations increased significantly in all four groups that received vitamin A supplementation, as determined by high-performance liquid chromatography. The intestinal levels of secretory immunoglobulin A and polymeric immunoglobulin receptor increased significantly with lipopolysaccharide challenge in the rats that received vitamin A supplementation starting on postnatal day 1. The rats in this group had higher numbers of CD8+ intestinal intraepithelial lymphocytes, CD11C + dendritic cells in the Peyer's patches and CD4+CD25+ T cells in the spleen compared with the vitamin A-deficient rats; flow cytometric analysis also demonstrated that vitamin A supplementation decreased the number of B cells in the mesenteric lymph nodes. Additionally, vitamin A supplementation during late gestation increased the numbers of CD8+ intestinal intraepithelial lymphocytes and decreased the numbers of B lymphocytes in the mesenteric lymph nodes. However, no significant differences in lymphocyte levels were found between the rats in the other two vitamin A supplement groups and the vitamin A-deficient group. In conclusion, the best recovery of a subset of lymphocytes in the offspring of gestational vitamin A-deficient rats and the greatest improvement in the intestinal mucosal immune response are achieved when vitamin A supplementation occurs during the early postnatal period.

Vitamin A deficiency induces structural and functional alterations in the molecular constituents of the rat hippocampus.

To date, no structural study has been carried out on the effects of vitamin A deficiency (VAD) on hippocampal macromolecules. Therefore, in the present study, the effect of dietary VAD on the structure, content and function of rat hippocampal molecules was investigated using Fourier transform IF spectroscopy. Male Wistar rats were randomly divided into three groups: an experimental group maintained on a vitamin A-deficient liquid diet (VAD, n 7); a control group maintained on a vitamin A-supplemented liquid diet (CON, n 9); a pure control group maintained on standard solid laboratory chow (PC, n 7). The PC group was included in the study to ensure that the usage of liquid diet did not influence the outcomes of VAD. Both the CON and PC groups were successfully discriminated from the VAD group by principal component analysis and hierarchical cluster analysis. The spectral analysis indicated a significant decrease in the contents of saturated and unsaturated lipids, cholesteryl esters, TAG and nucleic acids in the VAD group when compared with the CON group (P≤ 0·05). In addition, a significant decrease in membrane fluidity and a significant increase in lipid order (e.g. acyl chain flexibility) were observed in the VAD group (P≤ 0·001). The results of the artificial neural network analysis revealed a significant decrease in the α-helix structure content and a significant increase in the turn and random coil structure contents, indicating protein denaturation, in the VAD group when compared with the CON and PC groups (P≤ 0·05). Dietary exclusion of vitamin A for 3 months apparently had an adverse impact on compositional, structural and dynamical parameters. These changes can be due to increased oxidative stress, confirming the antioxidant protection provided by vitamin A when used as a dietary supplement at low-to-moderate doses.

Daily rhythms of catalase and glutathione peroxidase expression and activity are endogenously driven in the hippocampus and are modified by a vitamin A-free diet

ObjectivesAlterations in enzymatic antioxidant defense systems lead to a deficit of cognitive functions and altered hippocampal synaptic plasticity. The objectives of this study were to investigate endogenous rhythms of catalase (CAT) and glutathione peroxidase (GPx) expression and activity, as well as CREB1 mRNA, in the rat hippocampus, and to evaluate to which extent the vitamin A deficiency could affect those temporal patterns.MethodsRats from control and vitamin A-deficient (VAD) groups received a diet containing 4000 IU of vitamin A/kg diet, or the same diet devoid of vitamin A, respectively, during 3 months. Rats were maintained under 12-hour-dark conditions, during 10 days before the sacrifice. Circadian rhythms of CAT, GPx, RXRγ, and CREB1 mRNA levels were determined by reverse transcriptrase polymerase chain reaction in hippocampus samples isolated every 4 hours during a 24-hour period. CAT and GPx enzymatic activities were also determined by kinetic assays. Regulatory regions of clock and antioxidant enzymes genes were scanned for E-box, RXRE, and CRE sites.ResultsE-box, RXRE, and CRE sites were found on regulatory regions of GPx and CAT genes, which display a circadian expression in the rat hippocampus. VAD phase shifted CAT, GPx, and RXRγ endogenous rhythms without affecting circadian expression of CREB1.DiscussionCAT and GPx expression and enzymatic activity are circadian in the rat hippocampus. The VAD affected the temporal patterns antioxidant genes expression, probably by altering circadian rhythms of its RXR receptors and clock factors; thus, it would impair the temporal orchestration of hippocampal daily cognitive performance.

Differential effects of caloric intake and vitamin A status on insulin‐regulated Pck1 and Srebp1c expression in hepatocytes from Zucker fatty rats

Insulin‐regulated hepatic gene expression is impaired in Zucker fatty (ZF) rats. This is corrected by fasting or introducing vitamin A (VA) deficiency. VA deficiency reduces VA status and caloric intake. To separate these two effects, the insulin‐regulated Pck1 and Srebp1c expression were analyzed in primary hepatocytes from ZF rats. ZF rats after weaning were fed ad libitum a VA deficient (VAD), an isocaloric VA sufficient (VAS) diet ad libitum or the same amount of VAS diet consumed by the VAD group in the previous day for 8 weeks. The Pck1 and Srebp1c mRNA levels after insulin stimulation for 6 hours in the primary hepatocytes of these rats were determined by real‐time PCR. In hepatocytes of ZF rats fed the VAS diet, the insulin‐mediated inhibition of Pck1 and induction of Srebp1c expressions were impaired. This impairment was partially restored in hepatocytes of ZF rats fed the VAD diet. In hepatocytes of ZF rats pair‐fed the VAS diet, the insulin‐inhibited Pck1 expression, but not insulin‐induced Srebp1c expression, returned to normal. We conclude that insulin‐regulated expressions of Pck1 and Srebp1c in the ZF rat hepatocytes are respectively affected by caloric intake and VA status of the rats.Grant Funding Source: AHA (09SDG2140003)

Alteration in methylation pattern of GATA-4 promoter region in vitamin A-deficient offspring's heart

Epigenetics might explain correlations between lifestyle and risk of disease. Maternal diet has been shown to dynamically alter epigenetic regulation, including affecting DNA methylation status. This study was designed to test the hypothesis that GATA-4 gene methylation would lead to congenital heart defects in vitamin A-deficient offspring. Ten weaning female rats (VAN group) were fed with a diet which contents 4 IU vitamin A/g diet, while 20 rats (VAD group) were maintained on a diet without vitamin A. After 10 weeks of feeding, all the female rats were mated with normal male rats. The VAN group and a portion of VAD group rats were still given the same diet as before mating, while the rest of the rats from the VAD group (VADS group) were transferred to a diet with enough added vitamin A (10 IU/g diet) for the pregnancy cycle. The embryo hearts were dissected out at embryonic day 13.5 (E13.5) for observation of cardiac development, GATA-4 gene methylation status and the expression of DNA methyltransferases (DNMTs). Embryos from vitamin A-deficient group exhibited a high incidence of cardiac defects. High methylation was present in the CpG loci of GATA-4 gene with a low expression of GATA-4 mRNA from vitamin A-deficient group embryos. Moreover, up-regulation of DNMT1 and down-regulation of DNMT3a and DNMT3b expression were found in this group embryo. These findings show that aberrant methylation is one of key mechanisms to heart defects in vitamin A-deficient offspring. DNMTs play a critical role in this process.

Restoration of bone morphology by retinoic acid in a Vitamin A deficiency model in rats

These studies measured the effect of vitamin A deficiency (VAD) on bone structure and reabsorption as influenced by retinoic acid or cod liver oil in a rat model. Weanling rats received a vitamin A sufficient diet (controls) or a VAD diet for 9 weeks. From week ten to thirteen the VAD group split into 4 treatment groups: continued VAD, control, supplemented with retinoic acid or with cod liver oil containing vitamins A and D. At necropsy, femurs, liver, lungs and kidneys were formalin fixed and stained for histology. Bone osteoblast counts and histopathology scoring were performed. Femur thicknesses (400×, 3 sections/bone) were recorded as internal/external diameter ratios. Femurs of VAD rats had thinner cortical bone than controls (p<0.03). Addition to the VAD diet of retinoic acid, but not of cod liver oil restored the femurs to normal thickness. VAD rats had decreased numbers of both endosteal and periosteal osteoblasts vs controls (p<0.05) which were increased significantly by retinoic acid (p<0.002). Osteoclasts were not detected. VAD diet produced lung inflammation and emphysema and increased fat in the liver. Treatment with retinoic acid or cod liver oil restored pulmonary morphology but only retinoic acid restored the liver. Kidneys were normal. Retinoic acid therefore was the most effective in reversing VAD effects.

Daily patterns of clock and cognition‐related factors are modified in the hippocampus of vitamin A‐deficient rats

The circadian expression of clock and clock-controlled cognition-related genes in the hippocampus would be essential to achieve an optimal daily cognitive performance. There is some evidence that retinoid nuclear receptors (RARs and RXRs) can regulate circadian gene expression in different tissues. In this study, Holtzman male rats from control and vitamin A-deficient groups were sacrificed throughout a 24-h period and hippocampus samples were isolated every 4 or 5 h. RARα and RXRβ expression level was quantified and daily expression patterns of clock BMAL1, PER1, RORα, and REVERB genes, RORα and REVERB proteins, as well as temporal expression of cognition-related RC3 and BDNF genes were determined in the hippocampus of the two groups of rats. Our results show significant daily variations of BMAL1, PER1, RORα, and REVERB genes, RORα and REVERB proteins and, consequently, daily oscillating expression of RC3 and BDNF genes in the rat hippocampus. Vitamin A deficiency reduced RXRβ mRNA level as well as the amplitude of PER1, REVERB gene, and REVERB protein rhythms, and phase-shifted the daily peaks of BMAL1 and RORα mRNA, RORα protein, and RC3 and BDNF mRNA levels. Thus, nutritional factors, such as vitamin A and its derivatives the retinoids, might modulate daily patterns of BDNF and RC3 expression in the hippocampus, and they could be essential to maintain an optimal daily performance at molecular level in this learning-and-memory-related brain area.

The effect of vitamin A deficiency during pregnancy on anorectal malformations

Objective The aim of this study was to study the effect of vitamin A deficiency (VAD) on the embryological development of anorectal malformations (ARMs) and the enteric nervous system. Materials and Methods Female Sprague-Dawley rats were divided into 3 groups: VAD group, normal group (negative control), and ethylene thiourea (ETU) group (positive control) with a normal diet. On day 20 of pregnancy, cesarean section was performed on all rats. The incidence of ARMs in the fetal rats and Protein gene product 9.5 (PGP9.5) and S-100 protein expression by immunohistochemistry were determined. Results The incidence of ARMs in VAD and ETU groups was 64.8% (59/91) and 45.9% (61/133), respectively ( P > .05). Anorectal malformations were not found in the normal group. Protein gene product 9.5 and S-100 protein expression in the non-ARM rectums of the VAD group was lower than the ETU ( P = .0156 vs P = .0105) and normal groups ( P = .0091 vs P = .0024). There was no significant difference in PGP9.5 and S-100 protein expression between ETU and normal groups. In the ARM rectums, PGP9.5 and S-100 protein expression in the VAD group was lower than the ETU group ( P < .0001). Protein gene product 9.5 and S-100 protein expression was also lower in ARM than non-ARM rectums in the VAD and ETU groups ( P < .0001, P = .0203, and P = .0122, respectively). Conclusion Vitamin A deficiency during pregnancy may result in the embryological development of ARMs. Enteric nervous system development may be related to ARMs.

Deficiency of vitamin A delays bone healing process in association with reduced BMP2 expression after drill-hole injury in mice

Although it is predicted that vitamin A and its active form, retinoic acid, regulate osteoblast lineage, this has not been elucidated in growing mammalians. To clarify the direct effect of retinoic acid on bone, we observed the process of filling up newly generating bone into a drill-hole of the bone, which is understood as membranous ossification, in vitamin A-deficient mice. Mice were assigned to three groups: a vitamin A-deficient group (VAD), which was fed a diet without vitamin A from the 10th day of gestation to the end of the experiments; a vitamin A-deficient-sufficient group (VADS), which was fed a diet without vitamin A from the 10th day of gestation to 4 weeks of age; and a vitamin A-sufficient group (VAS), which was fed a standard diet to the end of the experiment. In mice at 10 weeks of age (day 0), a drill-hole injury was made with a diameter of 1 mm at the anterior portion of the diaphysis of the bilateral femurs. In VAD, retardation in repairing the drill-hole was demonstrated by in vivo micro-CT and histomorphometry from day7 and after surgery. During repair of the bone defect, increases of bmp2, dlx5, msx2, col1a1, and osteocalcin mRNA expression were suppressed, and runx2-p2 mRNA expression was accelerated in VAD. Implantation of BMP2 in the bone defect of VAD normalized the delayed bone healing and mRNA expressions. We concluded that vitamin A regulates bmp2 mRNA expression and plays a crucial role in osteoblastogenesis and bone formation.

Vitamin A deficiency results in dysregulation of lipid efflux pathway in rat kidney

The mechanisms of action of vitamin A deficiency (VAD) on lipid metabolism in the rat kidney were investigated in adult female rats and their offspring. The rats were randomized into three groups: (1) control, in which the mother and offspring received a normal diet (4000 retinol IU/kg diet) for 8 weeks; (2) VAD group, in which the mothers and offspring received a VAD diet (400 retinol IU/kg diet) for 8 weeks; (3) vitamin A-refed group, in which a group of pups on a VAD diet for 8 weeks received a complete diet (6500 retinol IU/kg diet) for 15 days. The lipid metabolism of the offsprings' kidneys and its relation to the expression of apolipoprotein B100 (Apo-B100), liver X receptor alpha (LXRalpha), and retinoid X receptor-alpha/beta (RXRalpha/beta) mRNA was analyzed. VAD was found to alter renal lipid metabolism and its immune environment due to the expression of Apo-B100. Compared with the control, VAD rats had significantly higher levels of transforming growth factor-beta 1 and lower levels of ABCA1, a key gene involved in cholesterol efflux and tissue lipid homeostasis. The expression of LXRalpha and RXRalpha/beta mRNA also decreased in the VAD rat kidney. Vitamin A refeeding reversed all of the changes. Lipid metabolism involved in renal reverse cholesterol transport may be mediated by decreasing the signaling through the ABCA1 cholesterol efflux pathway, which is significantly modified in kidneys of vitamin A-deficient rats.

Vitamin A Deficiency Increases Protein Catabolism and Induces Urea Cycle Enzymes in Rats

Chronic vitamin A deficiency induces a substantial delay in the rates of weight and height gain in both humans and experimental animals. This effect has been associated with an impaired nutrient metabolism and loss of body protein. Therefore, we analyzed the effect of vitamin A deficiency on endogenous proteolysis and nitrogen metabolism and its reversibility with all-trans retinoic acid (RA). Male weanling rats, housed in pairs, were pair-fed a vitamin A-deficient (VAD) or control diet until they were 60 d old. A group of deficient rats were further treated with daily intraperitoneal injections of all-trans RA for 10 d. Final body and tissue (i.e. liver and heart) weights were significantly lower and tissue:body weight ratios were similar in VAD rats and in controls. Conversely, the epididymal white fat:body weight ratio and the plasma concentrations of alanine aminotransferase and adiponectin were significantly higher in VAD rats, which also had hepatic macrovesicular lipid accumulations. Plasma and gastrocnemius muscle 3-methylhistidine, urine nitrogen, and plasma and urine urea concentrations were all significantly higher in the VAD group. The expression of the genes encoding urea cycle enzymes and their activities increased in VAD livers. These changes were partially reverted by all-trans RA. We propose that fuel partitioning in vitamin A deficiency may shift from fatty acids to protein catabolism as an energy source. Our results emphasize the importance of vitamin A on the energy balance control system and they provide an explanation for the role of vitamin A in protein turnover, development, and growth.

Effects of vitamin A deficiency on plasma glucose, insulin and leptin in rats

We have observed that vitamin A and its catalytic metabolites synergize with insulin to induce hepatic glucokinase gene expression. It has been known that retinoic acid (RA) can stimulate the expression of phosphoenolpyruvate carboxyl kinase gene. To better understand the role of vitamin A in glucose and lipid homeostasis, Zucker lean (female) rats were fed with vitamin A deficient (VAD) diet (TestDiet, #5822) and vitamin A sufficient (VAS) control diet (TestDiet, #5755) after weaning. When body weight gain stops in VAD group (a sign of vitamin A deficiency), animals were used to access the effect of vitamin A deficiency on glucose and lipid metabolism. All animals were fasted for six hours before their plasma and tissue samples were collected for analysis. To this end, levels of plasma glucose (153 ± 35.1 mg/dl), insulin (0.6 ±0.35 ng/ml), and leptin (1.3 ± 0.64 ng/ml) of VAD rats were all significantly lower than those (glucose, 176 ± 23.1 mg/dl; insulin, 1.3 ± 0.6 ng/ml; 4.0 ± 2.1 ng/ml, all P&lt;0.04)) of VAS fed rats. When VAD rats were fed with VAS diet, the plasma glucose level (150 ± 40 mg/dl) of VAD rats was significantly increased at three days (207 ± 62 mg/dl) and seven days (221 ± 45 mg/dl) after initiation of VAS diet (all P&lt;0.05). At the same time, plasma cholesterol level (49.6 ± 4.4 mg/dl) of VAD rats was also significantly increased at three days (74.6 ± 8.8 mg/dl) and seven days (83.9 ± 9.2 mg/dl) after resuming the VAS diet (all P&lt;0.004). These results demonstrated that vitamin A deficiency can result in the changes of plasma glucose and lipid homeostasis. Further work is warranted to understand the underlying molecular mechanisms.

The effect of vitamin A deficiency in maternal rats on tumor formation in filial rats

Purpose We established a vitamin A–deficient (VAD) model of pregnant rats to evaluate the effect of vitamin A deficiency in maternal rats on tumor formation in filial rats. Methods Ten pregnant Wistar rats were divided into 2 groups: (1) VAD group, 6 rats were given nonvitamin A diet from 2 weeks before mating till delivery and (2) normal diet (ND) group, 4 rats were given normal diet. Twenty random neonatal rats from each group were killed on the next day of delivery. The rest neonates were given normal diet for 1 year until killed. Serum levels of vitamin A, morphology of the kidney, incidence of tumor formation, and retinoid X receptor (RXR) α messenger RNA (mRNA) expression in renal tissue were assessed for the filial rats. Results Fifty-six and 49 neonatal rats were born for VAD group and ND group, respectively. The detection rate of nephrogenic rests (NRs) from neonates in VAD group (50%) was significantly higher than that in ND group (20%; P < .05). The incidence of nephroblastoma was 13.9% in filial rats of VAD group and 0% for ND group. The detection rate of NRs for filial rats of VAD group (30.6%) was significantly higher than that of ND group (6.9%; P < .01). The expression of RXR α mRNA in tumor tissue of the filial rats of VAD group (3.17 ± 0.15) was significantly lower than that in kidney tissue of ND group (3.58 ± 0.20; P < .01). Conclusion Deficiency in vitamin A for pregnant rats resulted in renal dysplasia, increased NRs, and higher incidence of nephroblastoma.

P-85 Is there a role for vitamin A on the regulation of IGF-I in children?

IGF system and vitamin A (VA) are important regulators of human growth and a wide range of physiological processes. Growth hormone and nutritional status are the main regulators of IGF system; however the role of the micronutrients is still not clear. The objective was to verify the effect of VA supplementation on IGF-I levels in VA deficient children. Ninety-four healthy children aged 5.5–11 years with regular follow-up in a pediatric clinic and no clinic evidence of vitamin A deficiency (VAD) entered the study. In order to access VA status serum retinol were determined by HPLC at baseline (BR) and 30 days (R30) after VA supplementation (200 000 IU of trans-retinyl palmitate) by +S30DR test (serum 30-day dose-response test). +S30DR was considered positive when (R30 −BR)× 100/R30 was 20%. IGF-I was also measured in both samples, by IRMA. Children were further divided in VAD and non-VAD. They were considered VAD if BR 1.05mmol/L or +S30DR positive. The samples were paired and compared using a nonparametric paired test. According to BR and +S30DR 24.5% and 28.7% of the children were considered VAD, respectively. IGF-I levels increased significantly with VA supplementation in the VAD group, either considering BR levels criterion (P = 0.001) or +S30DR test criterion (P = 0.004) while no difference was observed between baseline IGF-I and day-30 IGF-I in the non-VAD group. Baseline IGF-I was lower in the VAD than in the non-VAD group either considering BR (median: 190 vs. 260 mg/L) or +S30DR (median: 190 vs. 260mg/L) as criterion to VAD. No difference was found regarding day-30 IGF-I levels between VAD and non-VAD children. Conclusion: IGF-I levels increase after VA supplementation in children with subclinical VAD, these results suggest a possible role for VA on IGF-I regulation and support the idea that some of VA actions can be mediated by IGF-I, including the VA-supported growth.

Effect of Concurrent Vitamin A and Iodine Deficiencies on the Thyroid-Pituitary Axis in Rats

Deficiencies of vitamin A and iodine are common in many developing countries. Vitamin A deficiency (VAD) may adversely affect thyroid metabolism. The study aim was to investigate the effects of concurrent vitamin A and iodine deficiencies on the thyroid-pituitary axis in rats. Weanling rats (n = 56) were fed diets deficient in vitamin A (VAD group), iodine (ID group), vitamin A and iodine (VAD + ID group), or sufficient in both vitamin A and iodine (control) for 30 days in a pair-fed design. Serum retinol (SR), thyroid hormones (FT(4), TT(4), FT(3), and TT(3)), serum thyrotropin (TSH), pituitary TSHbeta mRNA expression levels, and thyroid weights were determined at the end of the depletion period. Compared to the control and ID groups, SR concentrations were about 35% lower in the VAD and VAD + ID groups (p < 0.001), indicating moderate VA deficiency. Comparing the VAD and control groups, there were no significant differences in TSH, TSHbeta mRNA, thyroid weight, or thyroid hormone levels. Compared to the control group, serum TSH, TSHbeta mRNA, and thyroid weight were higher (p < 0.05), and FT4 and TT4 were lower (p < 0.001), in the VAD + ID and ID groups. Compared to the ID group, TSH, TSHbeta mRNA, and thyroid weight were higher (p < 0.01) and FT(4) and TT(4) were lower (p < 0.001) in the VAD + ID group. There were no significant differences in TT3 or FT3 concentrations among groups. Moderate VAD alone has no measurable effect on the pituitary-thyroid axis. Concurrent ID and VAD produce more severe primary hypothyroidism than ID alone.

The enhancing role of vitamin A deficiency on chemically induced nephroblastoma in rats

Purpose Vitamin A plays an important role in the prevention of neoplasia. The occurrence of nephroblastoma, a common renal malignancy of childhood, is said to be closely correlated with retardation of differentiation of metanephric blastema. The aim of this study was to clarify the effect of vitamin A deficiency (VAD) in experimental nephroblastoma. Methods Sixty weaning outbred female Wistar rats weighing 40 to 50 g were injected with 0.35% dimethylhydrazine dihydrochloride (DMH) subcutaneously and divided into 2 groups. Animals were fed with diets containing vitamin A, normal diet (ND group; n = 30), and vitamin A–deficient diet (VAD group; n = 30). Serum concentrations of vitamin A on day 120 after DMH injection were assayed. The incidence of nephroblastomas in 2 groups was recorded. The renal tissues were prepared for morphological studies and WT1 messenger RNA (mRNA) detection on day 365 after DMH injection. Results The average serum concentrations of vitamin A in the ND group (2.60 ± 0.53 μmol/L) were significantly higher than that in the VAD group (0.51 ± 0.26 μmol/L, P < .05) 120 days after DMH injection. On day 365, the incidence of renal tumors in the VAD group (36.7%) was significantly higher than that of the ND group (13.3%, P < .05). Certain histological and ultrastructural features and WT1 mRNA expression patterns observed in these tumors showed that they had a resemblance to human nephroblastomas. Nephrogenic rests (NRs) could be seen in the adjacent normal renal parenchyma. The incidence of NRs in the VAD group (16.7%) was significantly higher than that in the ND group (3.3%, P < .05). The mutant WT1 mRNA expression levels in the VAD group (0.75 ± 0.11) were significantly higher than those in the ND group (0.24 ± 0.06, P < .05). Conclusions Vitamin A deficiency can increase development of nephroblastomas in rats, probably via a mechanism of elevated NR remnants and WT1 expression.

Effects of Mild Vitamin A Deficiency on Lung Maturation in Newborn Rats: A Morphometric and Morphologic Study

Objective: To evaluate the effects of a 60% vitamin A deficiency (VAD) on the two postnatal stages of lung development: alveolarization and microvascular maturation. Lungs from deficient rats were compared to age-matched controls. Study Design: Starting at 3 weeks before mating, female rats were maintained under a diet lacking vitamin A. Due to the slow depletion of the vitamin A liver stores the pregnant rats carried to term and delivered pups under mild VAD conditions. Mothers and offspring were then kept under the same diet what resulted in a mean reduction of vitamin A plasma concentration of about 60% vs. controls during the whole experimental period. Pups were sacrificed on days 4, 10 and 21 and their lungs fixed and analyzed by means of a combined morphologic and morphometric investigation at light and electron microscopic levels. Results: During the whole experiment, body weights of VAD animals were lower than controls with a significant decrease on day 10. On days 4, 10 and 21 the pulmonary structure was in a comparable gross morphologic state in both groups. Despite this morphologic normality, quantitative alterations in some functional parameters could be detected. On day 4, lung volume and the volume and surface area of air spaces were decreased, while the arithmetic mean barrier thickness and type 2 pneumocyte volume were increased in the VAD group. On day 21, some changes were again manifest mainly consisting in an augmentation of the vascularization and a decrease in interstitial volume in deficient animals. Conclusions: Mild VAD causes no gross disturbances in the postnatal phases of lung development in rats. However, a body weight-related transient retardation of lung maturation was detectable in the first postnatal week. At 3 weeks, the VAD lungs showed a more mature vascular system substantiated by an increase in volume of both capillary volume and the large non-parenchymal vessels. In view of these quantitative alterations, we suspect that mild VAD deregulates the normal phases of body and lung growth, but does not induce serious functional impairments.

Effect of vitamin A deficiency on cardiovascular function in the rat

Selected parameters of cardiovascular function were evaluated in vitamin A-deficient rats at 70 days of age. Resting heart rate was increased by an average of 100 bpm (21.4+/-2.7%), whereas resting systolic blood pressure was normal in vitamin A-deficient animals. The maximal contractile force developed per milligram weight of tissue by aortic rings excised from vitamin A-deficient animals was reduced in response to high potassium (-25.0+/-8.7%) and phorbol 12,13-dibutyrate (-36.8+/-8.4%) but was only slightly reduced in response to norepinephrine (-17.8+/-11.1%). Intimal rubbing to remove the endothelium had no effect on the loss in contractile responsiveness, and the relaxant response to acetylcholine was similar between control and vitamin A-deficient tissue groups. This suggests that the decrease in contractility of vascular smooth muscle from the vitamin A-deficient rats did not involve altered release of endothelium-derived vasoactive factors. Western blot analysis suggested a reduction in the protein levels of several differentiation markers including alpha-actin (-22%), calponin (-37%), desmin (-37%), and vinculin (-40%), whereas the level of PKCalpha was unchanged from control values. Our findings indicate a significant decrease in contractile responsiveness of aortic smooth muscle of the vitamin A-deficient rat that may be associated with a down regulation in the expression of contractile-related proteins.