Cod Liver Oil,but Not Retinoic Acid,Treatment Restores Bone Thickness in a Vitamin A-Deficient Rat

Vitamin A plays a prominent role for maintaining optimal bone status, but its impact upon the bone in response to vitamin A deficiency is not well defined. The purpose of this study was to evaluate how replenishing vitamin A by either whole food cod liver oil (COD) or the active metabolite of vitamin A, retinoic acid (RA), altered bone thickness of vitamin A-deficient (VAD) rats. Weanling rats were administered a control diet (CTRL) or VAD diet for 9 weeks. This was followed by four weeks of treatment in which the VAD group was divided into the following 4 subgroups: (1) VAD (9 weeks)-VAD (4 weeks); (2) VAD-CTRL; (3) VAD-COD; and (4) VAD-RA. Compared to controls, VAD rats had thicker bones which showed marked dysplasia. VAD-rats treated with COD produced a thinner bone that was not significantly different from that of untreated rats. In contrast, RA did not significantly change the thicker bone, and also had significantly greater periosteal and endosteal osteoblast numbers compared to VAD-COD. Active osteoclasts were not detected in VAD rats, nor during the treatment period. These findings suggest that the abnormal bone thickness in VAD rats appears to be more effectively restored to bone thickness of untreated control rats when treated with COD.     

Vitamin A in reproduction and development

The requirement for vitamin A in reproduction was first recognized in the early 1900's, and its importance in the eyes of developing embryos was realized shortly after. A greater understanding of the large number of developmental processes that require vitamin A emerged first from nutritional deficiency studies in rat embryos, and later from genetic studies in mice. It is now generally believed that all-trans retinoic acid (RA) is the form of vitamin A that supports both male and female reproduction as well as embryonic development. This conclusion is based on the ability to reverse most reproductive and developmental blocks found in vitamin A deficiency induced either by nutritional or genetic means with RA, and the ability to recapitulate the majority of embryonic defects in retinoic acid receptor compound null mutants. The activity of the catabolic CYP26 enzymes in determining what tissues have access to RA has emerged as a key regulatory mechanism, and helps to explain why exogenous RA can rescue many vitamin A deficiency defects. In severely vitamin A-deficient (VAD) female rats, reproduction fails prior to implantation, whereas in VAD pregnant rats given small amounts of carotene or supported on limiting quantities of RA early in organogenesis, embryos form but show a collection of defects called the vitamin A deficiency syndrome or late vitamin A deficiency. Vitamin A is also essential for the maintenance of the male genital tract and spermatogenesis. Recent studies show that vitamin A participates in a signaling mechanism to initiate meiosis in the female gonad during embryogenesis, and in the male gonad postnatally. Both nutritional and genetic approaches are being used to elucidate the vitamin A-dependent pathways upon which these processes depend.     

Turnover And Recycling Of Vitamin A In Vitamin A-Deficient And Sufficient Rats

The turnover rate and uptake of labeled retinol was found to be greater in the vitamin A-sufficient than in the vitamin A-deficient rats, though fractional turnover rates were about equal.     

维生素A缺乏对大鼠生精能力及睾丸标志酶活性的影响

目的　探讨维生素A缺乏对大鼠生精能力及睾丸标志酶活性的影响。方法　采用断乳期 2 1～ 2 3天Wistar雄性大鼠 ,体重 35～ 4 5g ,随机分为正常组 ,VA 缺乏组 ,分别饲喂正常饲料及无VA 的饲料 ,喂养 90天后 ,称重 ,乌拉坦麻醉 ,腹主动脉取血 ,采用荧光法测定血清VA 含量 ;摘取双侧睾丸和附睾。计算睾丸和附睾脏器系数 ,作精子相对计数及精子畸形率检测 ,测定睾丸中乳酸脱氢酶 (LDH)、碱性磷酸酶 (ALP)及γ -谷氨酰转肽酶 (GGT)活性 ,测定睾丸中总胆固醇 (CHOL)含量。结果　维生素A缺乏组雄鼠血清VA 含量明显低于正常组雄鼠 (t =4 1 5 1,P <0 0 1) ,睾丸、附睾的脏器系数下降 (t=12 12 ,3 83,P <0 0 1) ,精子数明显减少 (P <0 0 1) ,精子畸形率明显增高 (P <0 0 1)。睾丸中乳酸脱氢酶 (LDH)及γ -谷氨酶转肽酶 (GGT)活性明显降低 (t=3 2 2 ,3 0 7,P <0 0 1) ,碱性磷酸酶 (ALP)活性明显降低 (t′=2 83,P <0 0 5 ) ,睾丸中总胆固醇 (CHOL)含量明显降低 (t=3 37,P <0 0 1)。结论　维生素A缺乏影响雄性大鼠的生精能力、睾丸标志酶的活性及其胆固醇的含量     

Priming with Retinoic Acid,an Active Metabolite of Vitamin A,Increases Vitamin A Uptake in the Small Intestine of Neonatal Rats

Given that combined vitamin A (VA) and retinoic acid (RA) supplementation stimulated the intestinal uptake of plasma retinyl esters in neonatal rats, we administrated an RA dose as a pretreatment before VA supplementation to investigate the distinct effect of RA on intestinal VA kinetics. On postnatal days (P) 2 and 3, half of the pups received an oral dose of RA (RA group), while the remaining received canola oil as the control (CN). On P4, after receiving an oral dose of ³H-labeled VA, pups were euthanized at selected times (n = 4–6/treatment/time) and intestine was collected. In both CN and RA groups, intestinal VA mass increased dramatically after VA supplementation; however, RA-pretreated pups had relatively higher VA levels from 10 h and accumulated 30% more VA over the 30-h study. Labeled VA rapidly peaked in the intestine of CN pups and then declined from 13 h, while a continuous increase was observed in the RA group, with a second peak at 10 h and nearly twice the accumulation of ³H-labeled VA compared to CN. Our findings indicate that RA pretreatment may stimulate the influx of supplemental VA into the intestine, and the increased VA accumulation suggests a potential VA storage capacity in neonatal intestine.     

Vitamin a action on hepatic cholesterol biosynthesis

Vitamin A action on hepatic cholesterol biosynthesis in the rat animal model is nonconsistent and complex. Not only does Vitamin A enhance and depress cholesterol synthesis but the action of this nutrient is influenced by several factors such as: vitamin A status of the animal; form of vitamin A used; vitamin A metabolites; animal feeding regimen; substrate flux; and supernatant protein factors.     

边缘VA缺乏对大鼠胚胎骨骼发育及视黄酸受体表达的影响

目的研究边缘性维生素A(VA)缺乏及补充对大鼠胚胎骨骼发育的影响,及其与视黄酸受体(RARs)基因表达的关联性。方法初断乳SD雌性大鼠30只,按体重随机分为边缘性VA缺乏组(AM),边缘性VA缺乏妊娠0d(E0d)补充组(AS)和正常对照组(AN)。AM和AS组喂饲边缘性VA缺乏饲料(含VA0.4IU/gdiet),AN组喂饲VA充足饲料(含VA4IU/gdiet)。60d后与正常雄鼠交配。AS组自E0起改喂VA补充饲料(含VA10IU/gdiet)。于E12.5d和E19.5d将孕鼠处死,取胚胎。观测E19.5d胚胎骨骼发育指标;用荧光定量PCR及Westernblot检测E12.5d胚胎组织视黄酸受体的表达。结果AM组97.2%的E19.5d胚胎骨骼发育明显迟缓并出现多种骨骼畸形;E12.5d胚胎RARβ、RARγ表达水平明显下降。AS组胚胎各指标较AN组无异。结论视黄酸受体参与介导边缘性VA缺乏导致的大鼠胚胎骨骼发育异常,孕早期补充VA可有效预防骨骼畸形的发生。     

Illuminating the Role of Vitamin A in Skin Innate Immunity and the Skin Microbiome: A Narrative 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.     

A Potential Role for Vitamin D on HIV Infection?

Despite advances in the knowledge of vitamin D's potent immunomodulatory activity, its role on HIV disease progression is unknown. Decreased concentrations of 1α,25-hydroxyvitamin D₃, or 1,25(OH)₂D, the active form of vitamin D, have been reported among HIV-infected people and attributed to defects in renal hydroxylation and increased utilization. A few studies also described low levels of 25-hydroxyvitamin D₃, 25(OH)D, the vitamin obtained from solar synthesis and diet. An inverse association between 1,25(OH)₂D concentrations and mortality has been reported from a small cohort of HIV-infected adults, and some cross-sectional studies have indicated positive correlations between 1,25(OH)₂D and CD4+ cell counts. Additional observational studies are needed to confirm the associations between vitamin D status and HIV disease progression. These investigations would provide useful insights on the potential role of vitamin D supplementation to HIV-infected persons and the planning of intervention trials.     

Vitamin A supplementation modifies the antioxidant system in rats

BACKGROUND/OBJECTIVESIt has been shown that vitamin A supplementation has different effects on skeletal health and the antioxidant system. Deficiency or excess of this vitamin can lead to health problems. Vitamin A can work as either an antioxidant or prooxidant depending on its concentration. The present study was conducted to investigate the effects of different doses of vitamin A supplementation on the antioxidant system in rats.MATERIALS/METHODSForty Spargue-Dawley male rats were divided into four groups according to the dose of vitamin A received: 0 (A0), 4,000 (A1), 8,000 (A2), and 20,000 (A3) IU retinyl palmitate/kg diet. After a feeding period of 4 wks, lipid peroxide levels, glutathione concentration, antioxidant enzyme activities, and vitamins A and E concentrations were measured. Histopathological changes were observed in rat liver tissue using an optical microscope and transmission electron microscope.RESULTSLipid peroxide levels in plasma were significantly decreased in the A1 and A2 groups compared to the A0 rats. Erythrocyte catalase and hepatic superoxide dismutase activities of the A2 group were significantly higher than those of the A0 group. Hepatic glutathione peroxidase activity was significantly lower in the A3 group compared to the other groups. Total glutathione concentrations were significantly higher in the A1 and A2 groups than in the A0 group. Histological examination of liver tissue showed that excessive supplementation of vitamin A might lead to lipid droplet accumulation and nuclear membrane deformation.CONCLUSIONSThese results indicate that appropriate supplementation of vitamin A might have a beneficial effect on the antioxidant system in rats.     

孕期亚临床维生素A缺乏对胎鼠肺形态发育的影响

【目的】 探讨孕期亚临床维生素A(vitamin A,VA)缺乏对胎鼠肺形态发育的影响。 【方法】 建立孕期VA正常(vitamin A normal,VAN)和亚临床缺乏(marginal vitamin A deficiency,MVAD)动物模型,每组均于孕19 d剖宫取胎鼠,比较其体重、肺重、肝重和肺组织VA含量及其肺视黄酸受体(retinoic acid receptor,RAR)mRNAs的表达,HE染色光镜观察胎鼠肺的形态结构。 【结果】 1)胎鼠基本情况的比较 体重、肺重和肝重三个指标VAN组均显著高于MVAD组(P<0.05);2)胎肺大体形态比较 低倍镜(×200)与高倍镜(×400)下观察结果显示,VAN组肺泡样结构分布较规则,肺泡间隔较薄,肺实质发育较好,肺间质毛细血管较丰富,肺泡2型细胞较明显,大多处于小管期;而MVAD组上述指标均相对较差,发育幼稚,局部为小管期,大多为假腺体期;3)胎鼠肺单位组织VA水平 VAN组>MVAD组,差异均有统计学意义(P<0.05);4)胎鼠肺RAR-α、RAR-γ和RAR-β mRNAs表达水平VAN组P<0.05)。 【结论】 孕期VA水平不同能影响胎鼠基本发育、胎肺形态结构、肺单位组织VA水平及其RAR mRNAs的表达;孕期MVAD时其胎肺发育相对较差。     

Vitamin A in Skin and Hair: An Update

Vitamin A is a fat-soluble micronutrient necessary for the growth of healthy skin and hair. However, both too little and too much vitamin A has deleterious effects. Retinoic acid and retinal are the main active metabolites of vitamin A. Retinoic acid dose-dependently regulates hair follicle stem cells, influencing the functioning of the hair cycle, wound healing, and melanocyte stem cells. Retinoic acid also influences melanocyte differentiation and proliferation in a dose-dependent and temporal manner. Levels of retinoids decline when exposed to ultraviolet irradiation in the skin. Retinal is necessary for the phototransduction cascade that initiates melanogenesis but the source of that retinal is currently unknown. This review discusses new research on retinoids and their effects on the skin and hair.     

Plasma Vitamin A Homeostasis: The Relative Dose Response As A Measure Of Liver Vitamin A Reserves

Retinol levels in plasma of rats are constant and independent of dietary intake or liver stores above 10 μg per gram. If tissue needs of retinol are decreased by limiting protein intake or by feeding retinoic acid, plasma levels correspondingly decline. A single dose of newly supplied vitamin A leads to a short-term surge in plasma retinol level which may be a measure of liver reserves and vitamin A status.     

Association between Vitamin D Receptor Polymorphism and Serum Vitamin D Levels in Children with Low-Energy Fractures

Objective: Fractures of bones, especially forearm fractures, are very common in children and their number is increasing. This study was designed to determine the impact of vitamin D serum levels and vitamin D receptor (VDR) polymorphisms on the occurrence of low-energy fractures in children.

Methods: The study group consisted of 100 children with clinically relevant bone fractures and a control group consisted of 127 children without fractures. Total vitamin D [25(OH)D3 plus 25(OH)D2] serum concentrations were evaluated in every patient. Genotypes for 4 restriction fragment length polymorphisms of the vitamin D receptor gene (FokI, ApaI, TaqI, and BsmI) were determined by standard polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) techniques.

Results: Differences in concentrations of vitamin D were observed between the group with bone fractures (median = 12 ng/ml) and the control group (median = 16 ng/ml; p = 0.000044).

Higher levels of vitamin D reduced the risk of fracture by 1.06 times (p = 0.0005). No impact of particular VDR polymorphism on the occurrence of low-energy fractures in children was detected. However, there were significant differences in the prevalence of FokI polymorphism genotypes between the fracture and control groups (p = 0.05). Furthermore, the recessive “aa” genotype of ApaI polymorphism and the dominant “TT” genotype of TaqI polymorphism were associated with higher levels of vitamin D (p = 0.005 and p = 0.036, respectively).

Conclusions: Vitamin D deficiency is an independent risk factor for fractures in children. ApaI polymorphism recessive “aa” and TaqI polymorphism dominant “TT” genotypes are associated with higher levels of vitamin D in serum.     

INTERACTION OF RETINOL AND RETINOIC ACID WITH THE NUCLEUS

Intracellular binding proteins for retinol and retinoic acid have been described. A nuclear retinoic acid receptor also has been detected. Pure cellular retinol-binding protein, containing bound labeled retinol was found to bind to isolated, purified rat liver nuclei. The binding was highly specific and saturable, showing about 3 times 10⁵ specific binding sites per nucleus.     

VITAMIN A AND RETINOL-BINDING PROTEIN IN FETAL GROWTH AND DEVELOPMENT OF THE RAT

Studies on the transport of retinol and retinol-binding protein through the placenta and concentrations in the rat fetus at different stages of development tell much about their role in fetal growth and development.     

Retinoids in the Pathogenesis and Treatment of Liver Diseases

Vitamin A (VA), all-trans-retinol (ROL), and its analogs are collectively called retinoids. Acting through the retinoic acid receptors RARα, RARβ, and RARγ, all-trans-retinoic acid, an active metabolite of VA, is a potent regulator of numerous biological pathways, including embryonic and somatic cellular differentiation, immune functions, and energy metabolism. The liver is the primary organ for retinoid storage and metabolism in humans. For reasons that remain incompletely understood, a body of evidence shows that reductions in liver retinoids, aberrant retinoid metabolism, and reductions in RAR signaling are implicated in numerous diseases of the liver, including hepatocellular carcinoma, non-alcohol-associated fatty liver diseases, and alcohol-associated liver diseases. Conversely, restoration of retinoid signaling, pharmacological treatments with natural and synthetic retinoids, and newer agonists for specific RARs show promising benefits for treatment of a number of these liver diseases. Here we provide a comprehensive review of the literature demonstrating a role for retinoids in limiting the pathogenesis of these diseases and in the treatment of liver diseases.     

Vitamin A5/X,a New Food to Lipid Hormone Concept for a Nutritional Ligand to Control RXR-Mediated Signaling

Vitamin A is a family of derivatives synthesized from carotenoids acquired from the diet and can be converted in animals to bioactive forms essential for life. Vitamin A1 (all-trans-retinol/ATROL) and provitamin A1 (all-trans-β,β-carotene/ATBC) are precursors of all-trans-retinoic acid acting as a ligand for the retinoic acid receptors. The contribution of ATROL and ATBC to formation of 9-cis-13,14-dihydroretinoic acid (9CDHRA), the only endogenous retinoid acting as retinoid X receptor (RXR) ligand, remains unknown. To address this point novel and already known retinoids and carotenoids were stereoselectively synthesized and administered in vitro to oligodendrocyte cell culture and supplemented in vivo (orally) to mice with a following high-performance liquid chromatography-mass spectrometry (HPLC-MS)/UV-Vis based metabolic profiling. In this study, we show that ATROL and ATBC are at best only weak and non-selective precursors of 9CDHRA. Instead, we identify 9-cis-13,14-dihydroretinol (9CDHROL) and 9-cis-13,14-dihydro-β,β-carotene (9CDHBC) as novel direct nutritional precursors of 9CDHRA, which are present endogenously in humans and the human food chain matrix. Furthermore, 9CDHROL displayed RXR-dependent promnemonic activity in working memory test similar to that reported for 9CDHRA. We also propose that the endogenous carotenoid 9-cis-β,β-carotene (9CBC) can act as weak, indirect precursor of 9CDHRA via hydrogenation to 9CDHBC and further metabolism to 9CDHROL and/or 9CDHRA. In summary, since classical vitamin A1 is not an efficient 9CDHRA precursor, we conclude that this group of molecules constitutes a new class of vitamin or a new independent member of the vitamin A family, named “Vitamin A5/X”.     

维生素A缺乏对大鼠铁代谢影响

目的 研究维生素A(VA)缺乏对大鼠铁营养状况和肝脏转铁蛋白受体(TfR)mRNA表达的影响.方法 雄性SD大鼠52只,按体重随机分为4组,每组13只,Fe和VA正常对照组(I组),Fe正常VA完全缺乏组(II组),Fe正常VA轻度缺乏组(Ⅲ组),Fe和VA轻度缺乏组(IV组).喂饲8周后处死,测定血清VA、血红蛋白、血清铁、血清转铁蛋白受体、血清铁蛋白、肝脏铁含量,脾脏铁含量,并用逆转录聚合酶链反应(RT-PCR)法检测各组大鼠肝脏转铁蛋白受体(TfR)mRNA的表达.结果 结果与对照组比较,VA缺乏使血清铁、血清铁蛋白含量显著降低(P<0.05),血清转铁蛋白受体水平、脾脏铁含量显著升高(P<0.05),VA缺乏时肝脏TfRmRNA表达显著增强.结论 维生素A缺乏可能通过影响铁吸收、储存、转运变改体内铁的营养状况,VA缺乏时,肝脏可能通过铁调节蛋白(IRE-ⅠRP)途径使TfR mRNA的表达水平增加.