Retinyl Propionate Research Articles

51410 A Novel Combination of Niacinamide, Hexyl Resorcinol and Retinyl Propionate Provides Superior Anti-Aging Benefits in an 8-week Split-Face Study

51410 A Novel Combination of Niacinamide, Hexyl Resorcinol and Retinyl Propionate Provides Superior Anti-Aging Benefits in an 8-week Split-Face Study

Topical application of retinyl propionate, 4 hexyl resorcinol, and niacinamide reverses molecular and clinical features of ageing.

Topical tretinoin is the mainstay of treatment for photoageing, despite the risk of skin irritation. Cosmetic combination anti-ageing formulations may offer similar efficacy to tretinoin, while improving on tolerability. We aim to demonstrate facial appearance benefits of a novel triple-active cosmetic formulation containing 4-hexylresorcinol, retinyl propionate, and niacinamide and to identify transcriptomic biomarkers underpinning these benefits. A cosmetic prototype formulation containing 4-hexylresorcinol, retinyl propionate, and niacinamide was evaluated exvivo and in a clinical study. For exvivo experiments, the cosmetic formulation was applied for 3 days to healthy surgical discard skin from female donors aged 31-51 years, with tissues harvested for gene expression and histologic analyses. In the clinical study, females aged 47-66 years with moderate-to-severe overall visual photodamage on the face applied either topical 0.02% tretinoin or the cosmetic formulation to the face for 16 weeks and to forearms for 1 week, with forearm biopsies taken for gene expression analyses. Visual grading for facial photodamage and VISIA-CR images was taken throughout the clinical study. Safety was visually assessed during site visits, and adverse event monitoring was conducted throughout. Gene expression analyses in both studies revealed modulation of pathways associated with skin rejuvenation, with several genes of interest identified due to being implicated in ageing and differentially expressed following the application of the cosmetic formulation. Reversal of a consensus skin ageing gene signature was observed with the cosmetic formulation and tretinoin in the exvivo and clinical studies. Both the cosmetic formulation and tretinoin clinically improved the overall appearance of photoageing, crow's feet, lines, wrinkles, and pores. Adverse event reporting showed that the cosmetic formulation caused less skin irritation than tretinoin. In a double-blind clinical study, the novel triple-active cosmetic combination formulation improved the visual appearance of photoageing similarly to prescription tretinoin. The cosmetic formulation and tretinoin reversed a consensus gene signature associated with ageing. Together with adverse event reporting, these results suggest that the cosmetic formulation may be a well-tolerated and efficacious alternative to tretinoin for improving the visual features of photoageing.

Featured Cover

Journal of Cosmetic DermatologyVolume 22, Issue 7 p. i-i FEATURED COVEROpen Access Featured Cover First published: 20 June 2023 https://doi.org/10.1111/jocd.15824AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Graphical Abstract The cover image is based on the Original Article The synergistic effect of retinyl propionate and hydroxypinacolone retinoate on skin aging by Qianqian Wang et al., https://doi.org/10.1111/jocd.15662. Volume22, Issue7July 2023Pages i-i RelatedInformation

Lamellar gel containing emulsions as an effective carrier for stabilization and transdermal delivery of retinyl propionate

Emulsion systems are widely used as carriers for diverse actives processing moisturizing, anti-aging, whitening and other functions. Recently, emulsions containing lamellar gel phase have been attracting more and more research interests since it improves the physical stability of degradable actives. In the present work, o/w emulsions containing lamellar gel phase composed of ceteareth-20 (O-20) and mixed fatty alcohols (FA) were developed for retinyl propionate (RP) stabilization and transdermal delivery. The lamellar gel phase was confirmed by XRD combined with cryo-SEM, and main factors for lamellar gel phase formation were investigated and discussed. Moreover, effects of carrier oil on the emulsion properties were studied and the result showed that introduction of carrier oil benefits RP retention, rheological and transdermal properties. This study proves that O-20/FA based lamellar phase emulsion is promising system for RP stabilization and utilization in cosmetic formulations.

High Stability and Low Irritation of Retinol Propionate and Hydroxypinacolone Retinoate Supramolecular Nanoparticles with Effective Anti-Wrinkle Efficacy

Gravi-A nanoparticles, composed of retinyl propionate (RP) and hydroxypinacolone retinoate (HPR), were prepared by encapsulating the two using the high-pressure homogenization technique. The nanoparticles are effective in anti-wrinkle treatment with high stability and low irritation. We evaluated the effect of different process parameters on nanoparticle preparation. Supramolecular technology effectively produced nanoparticles with spherical shapes with an average size of 101.1 nm. The encapsulation efficiency was in the 97.98-98.35% range. The system showed a sustained release profile for reducing the irritation caused by Gravi-A nanoparticles. Furthermore, applying lipid nanoparticle encapsulation technology improved the transdermal efficiency of the nanoparticles, thereby allowing these to penetrate deep into the dermis layer to achieve precise and sustained release of active ingredients. Gravi-A nanoparticles can be extensively and conveniently used in cosmetics and other related formulations by direct application.

The synergistic effect of retinyl propionate and hydroxypinacolone retinoate on skin aging.

Aging is responsible for the majority of skin and soft tissue remolding in humans. Retinol and its derivatives or retinoids effectively intervene skin aging process. Nevertheless, retinoids usually induce skin intolerance, especially among the Chinese, and thus, their application to prevent skin aging is yet to be well accepted. The study of optimal composition and concentration of retinoids is necessary to offer strong antiaging efficacies with minimum irritations. Therefore, a better understanding of retinol and its derivatives is acutely needed to develop strategies to combat skin aging. In this study, we aimed to determine the optimal ratio of two retinol derivatives-hydroxypinacolone retinoate (HPR) and retinyl propionate (RP) in terms of dermal remodeling and skin aging prevention-and to investigate their synergistic antiaging effects both in vitro and in vivo. An in vitro human foreskin fibroblast (HFF-1) cell model was established to evaluate the cell viability of HPR and/or RP treatment. In addition, the antiaging and retinol receptor genes expressions in HFF-1 cells cotreated with HPR and RP were quantified. The in vivo adverse reaction evaluation of skincare serums containing various levels of retinol or the optimal HPR and RP combination termed Gravi-A was performed by 24 h patch tests in 33 subjects prior to the clinical research. Last but not the least, clinical research with 42 Chinese urban women was conducted to assess the in vivo antiaging efficacy of the skincare serum containing this optimal retinoid combination. The combination of HPR and RP at the weight ratio of 5:9 was shown to achieve the optimal in vitro antiaging performance. Coadministration of 5μg/mL HPR and 9μg/mL RP to HFF-1 cells promoted their proliferation at 24 h and synergistically enhanced the expressions of type IV collagen, CRBP-I, and RARB genes. In addition, the skincare serum containing HPR and RP combination at 5:9 weight ratio demonstrated superior in vivo anti-wrinkle and skin elasticity improvement benefits without any adverse reactions, while retinol in the same concentration exerted much higher adverse effect. Skin wrinkles, skin smoothness, TEWL, skin elasticity R2 and R5 were improved by 8.3%, 11.9%, 25.7%, 14.5%, and 22.6%, respectively, after 8-week use. Our results indicated the advanced antiaging effect of HPR and RP combination both in vitro and in vivo. In addition, little adverse effect was observed in this study, in comparison with retinol. This combination named as Gravi-A is a potential therapeutic strategy to prevent skin aging, especially for Chinese women.

Development and application of a SFC–DAD–MS/MS method to determine carotenoids and vitamin A in egg yolks from laying hens supplemented with β-carotene

β-Carotene, a provitamin A carotenoid, can be converted into vitamin A in animals’ bodies, and can also be accumulated intactly in many animal products. In this study, supercritical fluid chromatography–tandem mass spectrometry was utilized to determine β-carotene and different forms of vitamin A in eggs simultaneously. According to the results, β-carotene contained in yolk reached a plateau after about 2 weeks of supplementation. With an increase in dietary supplement level, the amount of β-carotene gradually increased, as well as slightly changing the yolk color. Moreover, the contents of retinoids including retinol, retinyl propionate, retinyl palmitate and retinyl stearate were also elevated in yolks with the β-carotene additive levels; meanwhile, the lutein and zeaxanthin decreased. On the whole, β-carotene in the diet of laying hens could be partially deposited in egg yolk, and the contents of vitamin A in yolk could be increased due to β-carotene bioconversion.

Hydrophobically modified inulin based nanoemulsions for enhanced stability and transdermal delivery of retinyl propionate

Nanovesicles are attractive for cosmetics application owing to their enhanced stability and transdermal delivery of active ingredients. Retinyl propionate (RP) is a promising anti-aging ingredient but it is usually unstable in formulations. In this work, we developed RP-loaded nanoemulsions using polymeric hydrophobically modified inulin (HMI), small-molecular polysorbate 20 (PS-20) as the main emusifiers and positively-charged behentrimonium chloride (BC) as a zeta-potential adjuster. Systematically optimizing the composition of the three emulsifiers led to small droplet size (<100 nm) and high physical stability of the nanoemulsions. Importantly, RP loaded in the nanoemulsions exhibited a high retention rate exceeding 80% after storage at 50 ℃ for 30 days. The superior RP stabilization and anti-coalescence property of the nanoemulsion could be attributed to the densely-packed, sterically-hindered and highly-charged interfacical layers composed of multiple emulsifiers at the oil-water interface. In addition, in vitro skin permeation experiments in a Franz diffusion cell suggested that the as-prepared nanoemulsions exhibited highly enhanced transdermal delivery of RP into the epidermis and dermis compared to the conventional emulsions. Therefore, the present work provides a feasible approach for more effective application of retinol esters in cosmetic formulations.

698 Retinol: A better solution for skin anti-aging than retinyl palmitate

The retinoids are a well-known anti-aging ingredients that show a clinical efficacy for wrinkle improvement. Retinol has been applied to many products as a representative ingredient for skin anti-aging cosmetics for many years. Recently, the use of retinol derivatives such as retinyl palmitate or retinyl propionate is increasing. The introduction of these derivatives is intended to use a more stable and to lower the risk of skin irritation. However, a technology to increase the stability of retinol has been developed and the problem has been sufficiently overcome. In this study, we conducted experiments comparing retinol and retinyl palmitate, a well-known retinol alternative, regarding the efficacy on skin anti-aging related markers in vitro. The efficacy of retinol on procollagen I expression, a representative dermal component for skin elasticity was increased in a dose-dependent manner in normal fibroblasts. Retinyl palmitate also induced procollagen I expression, but the effect of retinol was higher significantly. As a result of evaluating hyaluronic acid(HA) expression in normal keratinocytes, retinol showed a significant increase in HA secretion whereas retinyl palmitate did not induce HA secretion. The expression of MMP-1 increased by TNFα was reduced when retinol was treated, and retinyl palmitate had no inhibitory effect. Therefore, the efficacy of retinol was confirmed even in inflammatory aging in this study. In terms of antioxidant efficacy, retinyl palmitate had a lower radical scavenging activity compared to the high radical scavenging activity of retinol. Although not shown in this study, the antioxidant efficacy of retinol was superior to that of retinyl propionate. In conclusion, retinol can be expected to have an obvious effect than its derivatives by affecting the skin anti-aging targets. Retinol is a still attractive anti-aging ingredient in cosmetics.

594 The synergistic effect of retinyl propionate and hydroxypinacolone retinoate on skin early aging

Early aging is become increasingly important as the life expectancy rise rapidly. The occurrence of early aging is influenced by both extrinsic and intrinsic factors: the lower production rate of collagen and elastic fibers, the breaking of elastic fibers and collagen fibers caused by UV-induced metalloproteinases. Early aging shows a decline of the skin at multi-levels, which needs multi-effect active substances. Retinol and its derivatives are the most effective anti-aging substances. By increasing the synthesis of collagen and inducing dermal elastin and fibers, retinol and its derivatives effectively reduce wrinkles and improves skin firmness as well as elasticity.

Simultaneous Quantification of Vitamin A and Derivatives in Cosmetic Products by Liquid Chromatography with Ultraviolet Detection

Vitamin A (retinol) and some of its derivatives are a group of fat-soluble compounds used in cosmetic products as bioactive ingredients. Therefore, it is necessary to perform the quality control of final product to ensure their efficacy and safety. A simple and rapid method to determine retinol, retinal, retinyl acetate, retinyl propionate and retinyl palmitate in cosmetics is presented here. The method is based on vortex and/or ultrasound-assisted leaching of the analytes in ethanol followed by liquid chromatography with ultraviolet detection. The analytical performance of the method was evaluated. It has shown high levels of linearity, at least up to 100 µg mL−1; high precision with RSD values below 14% and high sensitivity with low MLODs ranging between 0.3 × 10−4 and 5.9 × 10−4 % w/w, which are enough to monitor these compounds in cosmetic products. The proposed method was successfully applied to seven commercial cosmetic samples to detect and quantify the target analytes, showing the method is suitable for its employment for quality control in cosmetic industries. Cosmetic samples were spiked at two levels of concentration and recovery values around 100% were obtained, showing no significant matrix effects and, therefore, external calibration was adequate for this determination.

Quality Control of Vitamins A and E and Coenzyme Q10 in Commercial Anti-Ageing Cosmetic Products

Vitamins A and E and coenzyme Q10 are common ingredients in anti-ageing cosmetic products. Within this study, we evaluated the quality of commercial cosmetics with vitamin A (35 products), vitamin E (49 products), and coenzyme Q10 (27 products) by using validated HPLC–UV methods. Vitamin A was determined as retinol, retinyl palmitate, retinyl propionate, β carotene, and hydroxypinacolone retinoate in concentrations ranging from 950 ng/g to 19 mg/g. Total vitamin A contents, expressed with retinol equivalents, ranged from 160 ng/g to 19 mg/g, and were above the maximum concentration recommended by the SCCS in six of the 35 tested cosmetics. The content-related quality control of 10 cosmetics with specified vitamin A content revealed significant deviations (between 0% and 400%) of the label claim. Vitamin E was determined as both tocopherol and tocopheryl acetate in concentrations between 8.5 µg/g and 16 mg/g. Coenzyme Q10 was determined as ubiquinone in 24 tested cosmetics, which labelled it, in concentrations between 4.2 µg/g and 100 µg/g. Labelling irregularities were observed in all three active compound groups, resulting in a significant share (42%) of improperly labelled cosmetic products. The results of this study reveal the need for stricter cosmetics regulation and highlight the importance of their quality control, especially by evaluating the contents of the active compounds, in their efficacy and safety assurance.

The Vitamin A and E Forms Influence Differently the Plasma Vitamin Concentrations in Newly Received Calves

Ten Holstein steer calves (105±3 kg) were used to evaluate bioavailability of two Vitamin A or E forms, “natural” (EA1) or “synthetic” (EA2), based on plasma vitamin concentrations during a 3-d period post injection(subcutaneous). Plasma retinyl palmitate and plasma Vitamin A concentration (retinol equivalent of all forms) was greater 24 and 48 h (P<0.01) post injection of retinyl palmitate vs retinyl propionate. Likewise, plasma retinol was greater (P = 0.04) 72 h post injection of retinyl palmitate. Plasma retinyl propionate was undetected for either treatment, indicative that it is not absorbed as a parent compound. Plasma retinyl palmitate, retinol and total Vitamin A concentrations peaked 24 h (P<0.01) post injection, decreasing toward baseline levels by 72 h post injection. Plasma tocopherol concentration was greater 24 h post injection (P<0.01) for calves injected with D-α-tocopherol vs DL-α-tocopherol. Levels were not different among treatments 48 h post injection (P>0.10). Plasma tocopherol concentrations were maximal (P<0.01) 24 h post injection of D-α-tocopherol, promptly decreasing by 72 h post injection (a level comparable to that observed with DL-α-tocopherol injection). We concluded that based on plasma concentrations, bioavailability of parenterally supplemented retinyl palmitate and D-α-tocopherol are greater than that of retinyl propionate and DL-α-tocopherol under acute Vitamin A or E supplementation.

Cover Image

The cover image is based on the Original Article The vitamin A ester retinyl propionate has a unique metabolic profile and higher retinoid-related bioactivity over retinol and retinyl palmitate in human skin models by Donald L. Bjerke et al., https://doi.org/10.1111/exd.14219.

Enhanced retinoid response by a combination of the vitamin A ester retinyl propionate with niacinamide and a flavonoid containing Ceratonia siliqua extract in retinoid responsive in vitro models.

Retinoids have been used for decades as efficacious topical agents to treat photoaged skin. The purpose of our present research is to evaluate whether the activity of the vitamin A ester retinyl propionate (RP) can be enhanced by niacinamide (Nam) and a flavonoid containing Ceratonia siliqua (CS) fruit extract in retinoid responsive in vitro models. Retinyl propionate was tested alone and in combination with Nam and CS in an RARα reporter cell line for promoter activation and compared to trans-retinoic acid (tRA) activation. These treatments were also tested in keratinocytes for gene expression profiling by qPCR using a panel of 40 retinoid responsive genes. tRA or RP elicited RARα reporter activation in a dose-dependent manner. The combination of 0.5μM or 2μM RP with 10mM Nam had a 56% and 95% signal increase compared to RP, respectively. The addition of 1% CS to 0.5μM or 2μM RP with 10mM Nam elicited a further increase of 114% and 156%, respectively, over RP and Nam combinations. All retinoids elicited an increase in expression of 40 retinoid sensitive genes over control levels. Of the 40 genes, 27 were enhanced by either 0.1μM RP or 0.5μM RP with 10mM Nam and 1% CS. Nam or CS had very modest activity in both models. The combination of RP with Nam and CS showed a higher retinoid response than RP in two separate retinoid responsive in vitro models. We hypothesize Nam and CS enhances RP activity by modulating metabolism to tRA via increasing NAD+ pools and inhibiting reduction of retinal (RAL) back to retinol, respectively. The findings provide evidence that this combination may have enhanced efficacy for treating the appearance of photoaged skin.

The vitamin A ester retinyl propionate has a unique metabolic profile and higher retinoid‐related bioactivity over retinol and retinyl palmitate in human skin models

Human skin is exposed daily to environmental stressors, which cause acute damage and inflammation. Over time, this leads to morphological and visual appearance changes associated with premature ageing. Topical vitamin A derivatives such as retinol (ROL), retinyl palmitate (RPalm) and retinyl propionate (RP) have been used to reverse these changes and improve the appearance of skin. This study investigated a stoichiometric comparison of these retinoids using in vitro and ex vivo skin models. Skin biopsies were treated topically to compare skin penetration and metabolism. Treated keratinocytes were evaluated for transcriptomics profiling and hyaluronic acid (HA) synthesis and treated 3D epidermal skin equivalents were stained for epidermal thickness, Ki67 and filaggrin. A retinoic acid receptor-alpha (RARα) reporter cell line was used to compare retinoid activation levels. Results from ex vivo skin found that RP and ROL have higher penetration levels compared with RPalm. RP is metabolized primarily into ROL in the viable epidermis and dermis whereas ROL is esterified into RPalm and metabolized into the inactive retinoid 14-hydroxy-4,14-retro-retinol (14-HRR). RP treatment yielded higher RARα activation and HA synthesis levels than ROL whereas RPalm had a null effect. In keratinocytes, RP and ROL stimulated similar gene expression patterns and pathway theme profiles. In conclusion, RP and ROL show a similar response directionality whereas RPalm response was inconsistent. Additionally, RP has a consistently higher magnitude of response compared with ROL or RPalm.

The Influence of Vitamin a on Molecular Bio-mineral Tissue Development in Pigs (P02-012-19)

ObjectivesThe objectives of this study were to identify differentially expressed transcripts and gene pathways in the vertebral bone of pigs receiving very high doses of vitamin A supplementation. Prior studies have ascertained that excessive vitamin A intake exhibits compartment-specific effects in bone tissue; these include regulating mineralisation genes in cortical bone containing bone marrow. Due to vertebral bone containing bone marrow, the hypothesis was that vitamin A will upregulate genes and pathways within vertebral bone that will favour bone mineralisation. MethodsA total of 64 indoor UK pigs, fed standard commercial diets, were split into 8 groups (n = 8 per group) and received daily dosing of retinyl propionate (RP) (0 up to 10,000 μg RP/kg BW) for 17 weeks. Vertebral bone was sampled from the 13th thoracic vertebrae and RNA was extracted. RNA from control pigs and pigs receiving 10,000 μg RP/kg BW was labelled and hybridised on an Agilent 4*44k microarray. Genespring was used to identify differentially expressed transcripts, and Ingenuity Pathway Analysis (IPA) was applied to recognise gene pathways associated with vitamin A supplementation. qRT-PCR was then performed to confirm differential gene expression on selected biomarkers. Kruskal-Wallis test was used to determine significant changes in gene expression in response to vitamin A dose. ResultsA total of 318 transcripts were observed to be differentially regulated > 2-fold in the vertebral bone of pigs receiving 10,000 μg RP/kg BW, 199 transcripts (62.6%) were observed to be upregulated (P < 0.05). Genes relating to Rho-GTPases and regulation of cytoskeletal dynamics, such as CDC42 and FLNA, persisted among canonical pathways (P < 0.05). qRT-PCR confirmed an 8.17-fold upregulation of FLNA in vertebral bone of pigs receiving 3000 μg RP/kg BW (P < 0.01), but no clear effect of treatment was observed on CDC42 expression (P = 0.147). ConclusionsDue to its role in the regulation of cytoskeletal reorganisation, of which subsequently affects both bone formation and resorption, the results suggest that high vitamin A intake potentially influences bone metabolism through interacting with the Rho-GTPase pathway. Funding SourcesBill and Melinda Gates Foundation.

The Effect of Chronic High Dose Vitamin a Supplementation on Lipid Metabolism in Adipose Tissue (P02-013-19)

ObjectivesThe objective of this study was to assess the impact of high-dose vitamin A (VA) on lipid metabolism. Previously, VA has been shown to enhance fat mobilisation, leading to a reduction in body fat. We hypothesise that hypervitaminosis A will increase expression of genes associated with lipid catabolism. MethodsTo induce chronic hypervitaminosis A, two groups of pigs (n = 8) were fed a commercial diet. The treatment group was additionally dosed, daily, with an oral supplement of retinyl propionate of 10,000 μg/KgBW for 17 weeks. To assess the impact of VA on lipid metabolism, a microarray analysis was performed to identify gene expression in adipose tissue. Differentially expressed transcripts and pathways were identified using Genespring and mapped to human orthologues for Ingenuity Pathway Analysis (IPA); gene fold changes were confirmed using qRT-PCR. Additionally, an untargeted UPLC-MS lipidomic analysis was carried out in serum samples to identify changes in lipd classes and their metabolites. ResultsIn dosed animals, significant increases in plasma retinol (0.66 μmol/L) and liver retinyl ester concentrations (11.98 μmol/g both P < 0.001), as well as an increase in serum NEFA of 92.84 μmol/L (P = 0.001) were observed. Gene expression fold changes in subcutaneous adipose tissue were related to mitochondrial dysfunction and lipid metabolism, including increased expression of MT-CYTB (↑4.78x, P < 0.05) and ATP5A1 (↑3.13x, P < 0.05). Metabolomics confirmed changes in lipids and their metabolites relevant to adipose tissue in blood (P = 0.05), namely a decrease in triacylglyceride concentration and increases in acyl carnitine and cardiolipin concentrations. ConclusionsAn integrated pathway is suggested to explain the role of vitamin A in leading to increased lipolysis, β-oxidation and oxidative phosphorylation, but when in excess, markers of mitochondrial dysfunction were observed. Funding SourcesFunded by the Bill and Melinda Gates foundation.

Effects of Chronic Hypervitaminosis a on Global Plasma Metabolome Changes and Liver Gene Expression (OR05-06-19)

ObjectivesConcerns about inadvertent chronic excessive vitamin A (VA) intakes due to overly frequent supplementation, fortification and voluntarily fortified products have been raised. Although chronic excessive VA intake can create liver abnormalities, clinically detectable signs of VA toxicity are rare, indicating the need for early biomarkers of tissue damage induced by excessive VA intake. MethodsTo identify early markers of VA toxicity, we induced chronic hypervitaminosis A in pigs (64 pigs, 8 per group) dosed with an oral supplement of retinyl propionate (0 up to 10,000 μg/KgBW) for 17 weeks. To assess the regulatory role of vitamin A in liver metabolism, a microarray analysis was performed to identify genetic regulation in liver tissue. Gene expression data were confirmed using qRT-PCR, and differentially expressed transcripts and pathways were identified using Genespring and Ingenuity Pathway Analysis (IPA). Additionally, two untargeted UPLC-MS assays (HILIC and C18 reversed phase) were applied to analyse plasma metabolites followed by univariate and multivariate analysis. ResultsMetabolomics analysis indicated that between 228 to 949 plasma metabolites were statistically significant between VA treated and control animals. The majority of metabolic changes observed in plasma were lipids, with ceramides, glycerophospholipids, lysoglycerophospholipids, sterol lipids and triacylglycerides enriched in both low and high VA dosed animals. Gene expression analysis confirmed significant changes in lipid metabolism, with pathways in metabolism of terpenoids and membrane lipids significantly increased by 2.4 fold. ConclusionsThe combined analysis of gene expression with untargeted metabolomics data confirm that changes in liver function and lipid metabolism offers an opportunity to develop a biomarker panel to diagnose pre-symptomatic hypervitaminosis A in humans. Funding SourcesSupported by the Bill and Melinda Gates foundation.

Biochemical Effects of Retinoid Derivatives on Mesenchymal Stem Cells In Vitro

The studies we performed targeted the effects of all-trans retinol (vitamin A) and some retinoid derivatives (including tretinoin or all-trans retinoic acid, retinyl propionate, 9-cis retinoic acid, 13-cis retinoic acid), as well as of tazarotenic acid on apoptosis of rat mesenchymal stem cells, cultured after isolation. Tazarotenic acid is considered to be relatively selective and a potent agonist for RARb and RARg and less for RARa. The same time, tazarotenic acid is not binding to RXRs (retinoid X receptors). The relevant analysis of our experimental results demonstrated that 13-cis retinoic acid was the most potent inducer of apoptosis of cultured mesenchymal stem cells of rat origin when compared to other retinoid derivatives, as follows: 13-cis retinoic acid ] 9-cis retinoic acid ] tazarotenic acid ] all-trans retinoic acid ] retinyl propionate ] retinol (or vitamin A). Very interesting and unexpected were the apoptotic effects of 1 �M tazarotenic acid for 24 hours in our experiments, very close to those induced by all-trans retinoic acid (tretinoin). The apoptosis induced by 13-cis retinoic acid, a principal activator of RARb and RARg, and that induced by 9-cis retinoic acid, a major activator of RXRs, suggests different pathways activated by these retinoid derivatives.