Retinol   中文名称: 维生素a

Retinoid receptors (RARs)

视黄醇是脂溶性维生素视黄醇。维生素A结合并激活类视黄醇受体（RARs），从而诱导某些癌症细胞类型的细胞分化和凋亡，并抑制致癌作用。维生素A在许多生理过程中起着至关重要的作用，包括视网膜的正常功能、靶组织的生长和分化、生殖器官的正常功能以及免疫功能的调节

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在这项研究中，尚不清楚哪种分子是诱导RAW264细胞中GSH产生增强的确切分子。然而，一种可能性是β-胡萝卜素被代谢成视黄醇，然后视黄醇实际上对GSH合成产生了增强作用。众所周知，β-胡萝卜素是维生素A的前体，由β-胡萝卜素转化而来的视黄醇（维生素A）具有潜在的生理功能，其中最具代表性的是视觉。据报道，在之前的研究中，用添加了β-胡萝卜素的培养基孵育后，RAW264细胞中未检测到视黄醇（Katsuura等人，2009）。同样，也有报道称，在RAW264细胞中未检测到β-胡萝卜素-15,15′-单加氧酶（BCMO1）的mRNA，该酶催化β-胡萝卜素或β-隐黄质产生类维生素A。与此相反，Zolberg等人报告称，在与9-顺式β-胡萝卜素孵育后，RAW264.7细胞中检测到BCMO1蛋白及其产物视黄醇（Zolberg-Relevy等人，2015）。另一种可能性是，β-胡萝卜素和视黄醇可能至少在一定程度上对RAW264细胞中GSH合成的增强具有几乎相同的作用[1]。

IMQ治疗的小鼠出现红斑、鳞屑和皮肤增厚。与对照组相比，IMQ治疗组有以下变化：1）血清和皮损皮肤中的白细胞介素（IL）-17A、IL-23和肿瘤坏死因子（TNF）-α水平显著升高（均p<0.001）；2） 皮损皮肤视黄醇水平略有升高（p=0.364），但血清视黄醇含量无明显变化；3） STRA6在皮损皮肤（p=0.021）和血清（p=0.034）中均上调；4） 血清中RBP4水平升高（p=0.042），但在病变皮肤中仅呈上升趋势（p=0.273）；5）介导视黄酸形成和转化的蛋白质和酶在病变皮肤中上调。[2]
结论：随着银屑病小鼠对维生素A需求的增加，视黄醇从循环系统转移到靶组织。RBP4、STRA6和从视黄醇到视黄酸的转化上调，这可能是银屑病皮肤病变形成机制的一部分。我们提出，形成了一种维持银屑病严重程度的正反馈机制[2]。

在这项研究中，研究人员评估了视黄醇和视黄酸（RA）增强小鼠培养的巨噬细胞系RAW264细胞内谷胱甘肽（GSH）水平的潜力，以研究RA信号通路是否参与β-胡萝卜素诱导的GSH增强。 [1]
方法和结果：我们检测了在添加了β-胡萝卜素和各种抑制剂（RA受体（RAR）α的ER50891、RARβ/γ的CD2665或所有亚型维甲酸X受体（RXR）的HX531）的培养基中培养的RAW264细胞中的GSH水平，以验证每种抑制剂对β-胡萝卜素的活性，以及在添加了各种刺激物（RARα的AM80、RARα中的CD2314、RARγ的CD437或RXR的SR11237）的培养基中培养的细胞中的谷胱甘肽水平，以将其活性与β-胡萝卜素有比较。我们还检测了在全反式RA或视黄醇补充培养基中培养的RAW264细胞中的GSH水平和谷氨酸半胱氨酸连接酶（GCL）表达。任何测试的拮抗剂都没有抑制GSH的产生，除了β-胡萝卜素外，没有激动剂诱导GSH的生产。视黄醇（但不是全反式RA）增强了GSH的合成，增加了GCL的表达，与β-胡萝卜素相似。 [1]
结论：RA信号通路可能不参与β-胡萝卜素诱导的RAW264细胞GSH水平的升高，而视黄醇与β-胡萝卜素一样，可以提高GSH水平和GCL表达。

Thirty mice were divided into four study groups: two groups underwent IMQ application for 3 or 6 days (groups A and B, respectively), and two groups underwent Vaseline application for 3 or 6 days (groups C and D, respectively). Blood and skin samples from both lesional and non-lesional areas of the mice were analyzed using enzyme-linked immunosorbent assays, hematoxylin and eosin staining, immunochemistry, real-time reverse transcription polymerase chain reaction, and RNA sequencing.[2]

Absorption, Distribution and Excretion
Readily absorbed from the normal gastrointestinal tract
Vitamin A is distributed into breast milk ... .
Less than 5% of circulating vitamin A is bound to lipoproteins in blood (normal), but may be up to 65% when hepatic stores are saturated because of excessive intake. The amount of vitamin A bound to lipoproteins may be increased in hyperlipoproteinemia. When released from liver, vitamin A is bound to retinol-binding protein (RBP). Most vitamin A circulates in the form of retinol bound to RBP.
Storage: Hepatic (approximately 2 years' adult requirements), with small amounts stored in kidney and lung tissues. Zinc is required for mobilization of vitamin A reserves in the liver.
More than 90% of the intake of preformed vitamin A is in the form of retinol esters, usually as retinyl palmitate. ... When a large excess is ingested, some of the vitamin escapes in the feces. ... Absorption ... is related to that of lipid and is enhanced by bile. ... Aqueous dispersions ... are absorbed more rapidly than are oily solution.
For more Absorption, Distribution and Excretion (Complete) data for VITAMIN A (9 total), please visit the HSDB record page.

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Metabolism / Metabolites
Hepatic. Retinol is conjugated with glucuronic acid; the B-glucuronide undergoes enterohepatic circulation and oxidation to retinol and retinoic acid. Retinoic acid undergoes decarboxylation and conjugation with glucuronic acid.
Retinol is converted to retinyl phosphate in epithelial tissues, and this intermediate is in turn metabolized to mannosylretinylphosphate in a reaction that is catalyzed by a microsomal enzyme and requires guanosine diphosphomannose as a glycosyl donor. ... /the vitamin A/ mediates transfer of mannose to specific glycoproteins.
Retinol is in part conjugated to form a beta-glucuronide, which undergoes enterohepatic circulation and is oxidized to retinal and retinoic acid.
Within the retina, all-trans-retinol is oxidized to retinal by alcohol dehydrogenases, and is then Isomerized to the 11-cis-isomer which combines with opsin in the rod to yield rhodopsin, and with different opsins in human cones to yield three different iodopsin pigments.
Retinoic acid (RA) is the bioactive metabolite of vitamin A (retinol) which acts on cells to establish or change the pattern of gene activity. Retinol is converted to RA by the action of two types of enzyme, retinol dehydrogenases and retinal dehydrogenases. In the nucleus RA acts as a ligand to activate two families of transcription factors, the RA receptors (RAR) and the retinoid X receptors (RXR) which heterodimerize and bind to the upstream sequences of RA-responsive genes.
Retinol has known human metabolites that include retinal and 4-Hydroxyretinol.
Hepatic. Retinol is conjugated with glucuronic acid; the B-glucuronide undergoes enterohepatic circulation and oxidation to retinol and retinoic acid. Retinoic acid undergoes decarboxylation and conjugation with glucuronic acid.
Half Life: 1.9 hours

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Biological Half-Life
1.9 hours
Hepatic reserves of vitamin A decrease with a half-life of about 50 days in animals ...

Toxicity Summary
Vision:Vitamin A (all-trans retinol) is converted in the retina to the 11-cis-isomer of retinaldehyde or 11-cis-retinal. 11-cis-retinal functions in the retina in the transduction of light into the neural signals necessary for vision. 11-cis-retinal, while attached to opsin in rhodopsin is isomerized to all-trans-retinal by light. This is the event that triggers the nerve impulse to the brain which allows for the perception of light. All-trans-retinal is then released from opsin and reduced to all-trans-retinol. All-trans-retinol is isomerized to 11-cis-retinol in the dark, and then oxidized to 11-cis-retinal. 11-cis-retinal recombines with opsin to re-form rhodopsin. Night blindness or defective vision at low illumination results from a failure to re-synthesize 11-cis retinal rapidly.
Epithelial differentiation: The role of Vitamin A in epithelial differentiation, as well as in other physiological processes, involves the binding of Vitamin A to two families of nuclear retinoid receptors (retinoic acid receptors, RARs; and retinoid-X receptors, RXRs). These receptors function as ligand-activated transcription factors that modulate gene transcription. When there is not enough Vitamin A to bind these receptors, natural cell differentiation and growth are interrupted.

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Interactions
Insulin antagonizes the /teratogenic/ effects /of vitamin A/.
The antithyroid compound methylthiouracil increases teratogenic effect /of vitamin A/.
Thyroxine antagonizes the teratogenic action of vitamin A.
In rats, the incidence of congenital abnormalities in the head due to hypervitaminosis A was increased greatly by appropriate administration of cortisone to the dams.
For more Interactions (Complete) data for VITAMIN A (19 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mouse ip 1510 mg/kg (10 day)
LD50 Mouse oral 2570 mg/kg (10 day)
LD50 Hen oral 3.15 - 3.7 g/kg body weight

[1]. Retinol but not retinoic acid can enhance the glutathione level, in a manner similar to β-carotene, in a murine cultured macrophage cell line. Food Sci Nutr . 2018 Jul 20;6(6):1650-1656.
[2]. Retinol and vitamin A metabolites accumulate through RBP4 and STRA6 changes in a psoriasis murine model. Nutr Metab (Lond) . 2020 Jan 13:17:5.

Therapeutic Uses
Vitamin A is indicated only for prevention or treatment of vitamin A deficiency states. Vitamin A deficiency may occur as a result of inadequate nutrition or intestinal malabsorption but does not occur in healthy individual receiving an adequate balanced diet. For prophylaxis of vitamin A deficiency, dietary improvement, rather than supplementation, is advisable. For treatment of vitamin A deficiency, supplementation is preferred. /Included in US product labeling/
Recommended intakes may be increased and/or supplementation may be necessary in infants receiving unfortified formula or in individuals with the following conditions (based on documented vitamin A deficiency): Diarrhea; gastrectomy; hyperthyroidism; infections, chronic; intestinal diseases: celiac, diarrhea, topical sprue, regional enteritis; malabsorption syndromes associated with pancreatic insufficiency: pancreatic disease, cystic fibrosis; measles; protein deficiency, severe, stress, prolonged; xerophthalmia. /Included in US product labeling/
Some unusual diets (e.g., reducing diets that drastically restrict food selection, especially the fat-containing foods) may not supply minimum daily recommended intakes of vitamin A. Supplementation is necessary in patients receiving total parenteral nutrition (TPN) or undergoing rapid weight loss or in those with malnutrition, because of inadequate dietary intake.
Recommended intakes for most vitamins and minerals are increased during pregnancy. Many physicians recommend that pregnant women receive multivitamin and mineral supplements, especially those pregnant women who do not consume an adequate diet and those in high-risk categories (i.e., women carrying more than one fetus, heavy cigarette smokers, and alcohol and drug abusers). Taking excessive amounts of a multivitamin and mineral supplement may be harmful to the mother and/or fetus and should be avoided.
For more Therapeutic Uses (Complete) data for VITAMIN A (7 total), please visit the HSDB record page.

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Drug Warnings
Pregnancy risk category: X /CONTRAINDICATED IN PREGNANCY. Studies in animals or humans, or investigational or post-marketing reports, have demonstrated positive evidence of fetal abnormalities or risk which clearly outweights any possible benefit to the patient./ /Parenteral vitamin A/
Doses of vitamin A that do not exceed the physiologic requirement are usually nontoxic.
There are insufficient data to show that vitamin A may reduce the occurrence of certain types of cancer.
... Vitamin A has not been proven effective for treatment of renal calculi, hyperthyroidism, anemia, degenerative conditions of the nervous system, sunburn, lung diseases, deafness, osteoarthritis, inflammatory bowel disease, or psoriasis.
For more Drug Warnings (Complete) data for VITAMIN A (9 total), please visit the HSDB record page.

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Pharmacodynamics
Vitamin A is effective for the treatment of Vitamin A deficiency. Vitamin A refers to a group of fat-soluble substances that are structurally related to and possess the biological activity of the parent substance of the group called all-trans retinol or retinol. Vitamin A plays vital roles in vision, epithelial differentiation, growth, reproduction, pattern formation during embryogenesis, bone development, hematopoiesis and brain development. It is also important for the maintenance of the proper functioning of the immune system.

C20H30O

286.45

286.229

C, 83.86; H, 10.56; O, 5.59

68-26-8

445354

Solvated crystals from polar solvents, such as methanol or ethyl formate

1.0±0.1 g/cm3

421.2±14.0 °C at 760 mmHg

61-63 °C(lit.)

147.3±16.4 °C

0.0±2.3 mmHg at 25°C

1.549

6.84

20.23

1

1

5

21

496

0

CC1=C(C(CCC1)(C)C)/C=C/C(=C/C=C/C(=C/CO)/C)/C

FPIPGXGPPPQFEQ-OVSJKPMPSA-N

InChI=1S/C20H30O/c1-16(8-6-9-17(2)13-15-21)11-12-19-18(3)10-7-14-20(19,4)5/h6,8-9,11-13,21H,7,10,14-15H2,1-5H3/b9-6+,12-11+,16-8+,17-13+

(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraen-1-ol

Prepalin; Testavol; Vitamin A; alcohol All-trans-retinol; all-trans-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol; Axerophthol; Vafol; Avibon; Afaxin; Retinol; Aoral; Biosterol; Vitamin A Chocola A; Alphasterol;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。