Absorption, Distribution and Excretion
Vitamin A is readily absorbed by the normal gastrointestinal tract. It is distributed into breast milk… Normally, less than 5% of circulating vitamin A in the blood is bound to lipoproteins, but this can reach as high as 65% when excessive intake leads to liver saturation. In hyperlipoproteinemia, the amount of vitamin A bound to lipoproteins may increase. After being released from the liver, vitamin A binds to retinol-binding protein (RBP). Most vitamin A circulates as retinol bound to RBPs. Storage: Primarily stored in the liver (approximately equivalent to two years' worth of an adult's requirement), with smaller amounts stored in the kidneys and lung tissue. Zinc is essential for the liver to mobilize vitamin A reserves. Over 90% of preformed vitamin A intake is in the form of retinyl esters, typically retinyl palmitate. …When excessive intake occurs, some vitamin A is excreted in feces. …Absorption…is related to lipid absorption and is promoted by bile. …Aqueous dispersions…are absorbed faster than oily solutions. For more complete data on the absorption, distribution, and excretion of vitamins A (9 types), please visit the HSDB record page.

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Metabolism/Metabolites
Hepatic metabolism. Retinol conjugates with glucuronic acid; β-glucuronide is oxidized to retinol and retinoic acid via the enterohepatic circulation. Retinic acid undergoes decarboxylation and conjugates with glucuronic acid.
Retinol is converted to retinyl phosphate in epithelial tissues. This intermediate is further metabolized to mannosyl retinyl phosphate under the catalysis of microsomal enzymes, using guanosine diphosphate as a glycosyl donor. Vitamin A mediates the transfer of mannose to specific glycoproteins. Retinol partially conjugates to form β-glucuronide, which is oxidized to retinal and retinoic acid via the enterohepatic circulation. In the retina, all-trans retinol is oxidized to retinal by alcohol dehydrogenases, and then isomerized to the 11-cis isomer. The 11-cis isomer binds to opsins in rod cells to form rhodopsin, and binds to different opsins in cone cells to form three different iodopurine pigments. Retinoic acid (RA) is a bioactive metabolite of vitamin A (retinol), which acts on cells to establish or alter gene activity patterns. Retinol is converted to retinoic acid by two enzymes: retinol dehydrogenase and retinal dehydrogenase. In the cell nucleus, retinoic acid (RA) acts as a ligand to activate two types of transcription factors: retinoic acid receptor (RAR) and retinoid X receptor (RXR). RAR and RXR form heterodimers and bind to the upstream sequence of RA-responsive genes. Known metabolites of retinol in the human body include retinal and 4-hydroxyretinol. In the liver, retinol binds to glucuronic acid; β-glucuronide is oxidized to retinol and retinoic acid via the enterohepatic circulation. Retinoic acid is decarboxylated and binds to glucuronic acid.
Half-life: 1.9 hours

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Biological half-life
1.9 hours
The vitamin A reserves in animal liver decrease with a half-life of approximately 50 days…

Toxicity Summary
Vision: Vitamin A (all-trans retinol) is converted in the retina to the 11-cis isomer of retinaldehyde, namely 11-cis retinaldehyde. 11-cis retinaldehyde functions in the retina, converting light signals into the neural signals required for vision. 11-cis retinaldehyde binds to opsin in rhodopsin and isomerizes to all-trans retinaldehyde under light. This process triggers nerve impulses transmitted to the brain, enabling the perception of light. Subsequently, all-trans retinaldehyde is released from opsin and reduced to all-trans retinol. All-trans retinol isomerizes to 11-cis retinol in the dark, and then oxidizes to 11-cis retinaldehyde. 11-cis retinaldehyde recombines with opsin to form rhodopsin. Night blindness or low-light vision impairment is caused by the inability to rapidly resynthesize 11-cis retinaldehyde.
Epithelial Differentiation: Vitamin A plays a role in epithelial differentiation and other physiological processes involving the binding of vitamin A to two classes of nuclear retinol receptors (retinoic acid receptor, RAR; and retinol X receptor, RXR). These receptors act as ligand-activated transcription factors, regulating gene transcription. When vitamin A is insufficient to bind to these receptors, natural cell differentiation and growth are disrupted.

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Interactions
Insulin antagonizes the teratogenic effects of vitamin A.
The antithyroid compound methylthiouracil enhances the teratogenic effects of vitamin A.
Thyroxine antagonizes the teratogenic effects of vitamin A.
In rats, appropriate injection of cortisone into dams significantly increased the incidence of congenital head malformations caused by vitamin A overdose.
For more complete data on vitamin A interactions (19 in total), please visit the HSDB record page.

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Non-human toxicity values
Mouse intraperitoneal LD50: 1510 mg/kg (10 days)
Mouse oral LD50: 2570 mg/kg (10 days)
Chicken oral LD50: 3.15 - 3.7 g/kg body weight

Therapeutic Uses
Vitamin A is intended for the prevention or treatment of vitamin A deficiency only. Vitamin A deficiency can be caused by malnutrition or malabsorption in the gut, but healthy individuals will not develop vitamin A deficiency if they consume an adequate and balanced diet. To prevent vitamin A deficiency, dietary improvements are recommended, not vitamin A supplementation. To treat vitamin A deficiency, vitamin A supplementation is recommended. /Included on US product label/
For infants consuming unfortified formula or individuals with the following conditions (based on a confirmed vitamin A deficiency), increased vitamin A intake and/or vitamin A supplementation is recommended: diarrhea; gastrectomy; hyperthyroidism; chronic infections; intestinal diseases: celiac disease, diarrhea, localized stomatitis, regional enteritis; malabsorption syndromes associated with pancreatic insufficiency: pancreatic disease, cystic fibrosis; measles; severe protein deficiency, chronic stress; dry eye syndrome. /Included on US product label/
Some special diets (e.g., heavily restrictive diets, especially low-fat diets containing fatty foods) may not provide the minimum recommended daily intake of vitamin A. Patients receiving total parenteral nutrition (TPN), those experiencing rapid weight loss, or those suffering from malnutrition may require vitamin A supplementation due to insufficient dietary intake. The recommended intake of most vitamins and minerals increases during pregnancy. Many physicians recommend multivitamin and mineral supplements for pregnant women, especially those with insufficient dietary intake and those in high-risk groups (e.g., pregnant women carrying multiple fetuses, heavy smokers, and alcohol and drug addicts). Overdosing on multivitamin and mineral supplements may be harmful to the mother and/or fetus and should be avoided. For more complete data on the therapeutic uses of vitamin A (7 types), please visit the HSDB record page.

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Drug Warnings
Pregnancy Risk Category: X / Contraindicated during pregnancy. Animal or human studies, or investigational reports or post-marketing reports, have demonstrated a risk or hazard to fetus that clearly outweighs any potential benefit to the patient. / /Parenteral Vitamin A/
Vitamin A in doses not exceeding physiological requirements is generally non-toxic.
There is insufficient data to suggest that vitamin A reduces the incidence of certain types of cancer.
...Vitamin A has not been proven effective in treating kidney stones, hyperthyroidism, anemia, neurodegenerative diseases, sunburn, lung disease, deafness, osteoarthritis, inflammatory bowel disease, or psoriasis.
For more complete data on drug warnings for Vitamin A (9 in total), please visit the HSDB records page.

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Pharmacodynamics
Vitamin A is effective in treating Vitamin A deficiency. Vitamin A refers to a group of fat-soluble substances whose structure is related to all-trans retinol or retinol (or simply retinol) and has the same biological activity. Vitamin A plays a vital role in vision, epithelial differentiation, growth, reproduction, pattern formation during embryogenesis, bone development, hematopoiesis, and brain development. It is also essential for maintaining the normal function of the immune system.

C20H30O

286.4516

286.229

11103-57-4

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

62-64ºC

147.3±16.4 °C

0.0±2.3 mmHg at 25°C

1.549

6.84

1

1

5

21

496

0

OC/C=C(/C=C/C=C(/C=C/C1=C(C)CCCC1(C)C)\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

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

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)