ascorbic-acid and retinol-palmitate

Cancer development has been directly related to oxidative stress. During chemotherapy, some cancer patients use dietary antioxidants to avoid nutritional deficiencies due to cancer treatment. Among the antioxidants consumed, there are vitamins, including retinyl palmitate (PR) and ascorbic acid (AA), which have the capacity to reduce free radicals formation, protect cellular structures and maintain the cellular homeostasis. This systematic review evaluated the antioxidant and antitumor mechanisms of retinol palmitate (a derivative of vitamin A) and/or ascorbic acid (vitamin C) in cancer-related studies. Ninety-seven (97) indexed articles in the databases PubMed and Science Direct, published between 2013 and 2017, including 23 clinical studies (5 for every single compound while 13 in interaction) and 74 non-clinical studies (37 for retinol palmitate, 36 for ascorbic acid and 1 in interaction) were considered. Antioxidant and antitumor effects, with controversies over dosage and route of administration, were observed for the test compounds in their isolated form or associated in clinical studies. Prevention of cancer risks against oxidative damage was seen in lower doses of retinol palmitate and/or vitamin C. However, at high doses, they can generate reactive oxygen species, cytotoxicity and apoptosis in test systems. Non-clinical studies using cell lines have allowed understanding the mechanisms related to antioxidants and antitumor effects of the isolated compounds, however, studies on vitamin interactions, acting as antioxidants and/or antitumor are still rare and controversial. More studies, mainly related to modulation of antineoplastic drugs are needed for understanding the risks and benefits of their use during treatment in order to achieve effectiveness in cancer therapy and patient's quality of life.

Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Diterpenes; Humans; Reactive Oxygen Species; Retinyl Esters; Vitamin A

Experimental evidence indicates a strong connection between oxidative damage, cancer, and aging. Epidemiological observations suggest that a diet rich in fruits and vegetables is associated with lower incidence of some cancers and longer life expectancy; since fruits and vegetables contain natural antioxidants, a considerable effort has been dedicated to understanding their effects in experimental studies and in human trials.. A: Effects of antioxidant-containing food and supplements on oxidation damage in humans. Intervention trials employing a variety of biomarkers have shown either a slight decrease in oxidation damage or no effect. B: Effects of selected antioxidants on mortality and cancer incidence. β-carotene and α-tocopherol, alone or in combination, increase cardiovascular and all-cause mortality or have no effect. In some studies, β-carotene and retinyl palmitate significantly increase the progression of lung cancer and aggressive prostate cancer. Protection against cardiovascular mortality or no effect of vitamin E has been reported, with an increase of all-cause mortality at dosages greater than 150 IU/day. Selenium showed beneficial effects on gastrointestinal cancer and reduced the risk of lung cancer in populations with lower selenium status. For multivitamin and mineral supplementation, no significant reduction of mortality or cancer incidence was observed, but some reports indicate a possible preventive effect in cervical cancer.. The majority of supplementation studies indicate no variation of general mortality and of cancer incidence or a detrimental effect on both. Antioxidant supplements so far tested seem to offer no improvement over a well-balanced diet, possibly because of the choice of the substances tested or of an excessive dosage. However, new natural or synthetic compounds effective in vitro and in experimental studies might still be worth investigating in human trials.

Topics: Aging; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Dietary Supplements; Diterpenes; Heart Diseases; Humans; Incidence; Life Expectancy; Neoplasms; Randomized Controlled Trials as Topic; Retinyl Esters; Selenium; Trace Elements; Vitamin A; Vitamin E; Vitamins

The General Population Nutrition Intervention Trial was a randomized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991, in which 29,584 adult participants in Linxian, China, were given daily vitamin and mineral supplements. Treatment with "factor D," a combination of 50 microg selenium, 30 mg vitamin E, and 15 mg beta-carotene, led to decreased mortality from all causes, cancer overall, and gastric cancer. Here, we present 10-year follow-up after the end of active intervention.. Participants were assessed by periodic data collection, monthly visits by village health workers, and quarterly review of the Linxian Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the cumulative effects of four vitamin and mineral supplementation regimens were calculated using adjusted proportional hazards models.. Through May 31, 2001, 276 participants were lost to follow-up; 9727 died, including 3242 from cancer (1515 from esophageal cancer and 1199 from gastric cancer). Participants who received factor D had lower overall mortality (HR = 0.95, 95% CI = 0.91 to 0.99; P = .009; reduction in cumulative mortality from 33.62% to 32.19%) and gastric cancer mortality (HR = 0.89, 95% CI = 0.79 to 1.00; P = .043; reduction in cumulative gastric cancer mortality from 4.28% to 3.84%) than subjects who did not receive factor D. Reductions were mostly attributable to benefits to subjects younger than 55 years. Esophageal cancer deaths between those who did and did not receive factor D were not different overall; however, decreased 17% among participants younger than 55 (HR = 0.83, 95% CI = 0.71 to 0.98; P = .025) but increased 14% among those aged 55 years or older (HR = 1.14, 95% CI = 1.00 to 1.30; P = .047) [corrected]. Vitamin A and zinc supplementation was associated with increased total and stroke mortality; vitamin C and molybdenum supplementation, with decreased stroke mortality.. The beneficial effects of selenium, vitamin E, and beta-carotene on mortality were still evident up to 10 years after the cessation of supplementation and were consistently greater in younger participants. Late effects of other supplementation regimens were also observed.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; China; Confounding Factors, Epidemiologic; Dietary Supplements; Diterpenes; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Malnutrition; Micronutrients; Middle Aged; Molybdenum; Neoplasms; Niacin; Odds Ratio; Retinyl Esters; Riboflavin; Risk Factors; Selenium; Vitamin A; Vitamins; Zinc Oxide

Omeprazole (OME), a most frequently used proton pump inhibitor in gastric acidosis, is evident to show many adverse effects, including genetic instability. This study evaluated toxicogenic effects of OME in Mus musculus.. For this study, 40 male Swiss mice were divided into 8 groups (n = 5) and treated with OME at doses of 10, 20, and 40 mg/kg and/or treated with the antioxidants retinol palmitate (100 IU/kg) and ascorbic acid (2.0 μM/kg). Cyclophosphamide 50 mg/kg, (cytotoxic agent) and the vehicle were served as positive and negative control group, respectively. After 14 days of treatment, the stomach cells along with the bone marrow and peripheral blood lymphocytes were collected and submitted to the comet assay (alkaline version) and micronucleus test. Additionally, hematological and biochemical parameters of the animals were also determined inspect of vehicle group.. The results suggest that OME at all doses induced genotoxicity and mutagenicity in the treated cells. However, in association with the antioxidants, these effects were modulated and/or inhibited along with a DNA repair capacity.. Taken together, antioxidants (such as retinol palmitate and ascorbic acid) may be one of the best options to counteract OME-induced cytogenetic instability.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Comet Assay; Cyclophosphamide; Diterpenes; DNA Repair; Dose-Response Relationship, Drug; Male; Mice; Mutagenesis; Omeprazole; Proton Pump Inhibitors; Retinyl Esters

Topics: Animals; Ascorbic Acid; Cell Line, Tumor; Cell Survival; Chromosome Aberrations; Cyclophosphamide; Diterpenes; Hydrogen Peroxide; Mice; Micronucleus Tests; Omeprazole; Oxidative Stress; Retinyl Esters; Saccharomyces cerevisiae; Vitamin A

Omeprazole (OME) is a proton pump inhibitor used for the treatment of various gastric and intestinal disease; however, studies on its effects on the genetic materials are still restricted. The present study aimed to evaluate possible toxicogenic effects of OME in Allium cepa meristems with the application of cytogenetic biomarkers for DNA damage, mutagenic, toxic and cytotoxic effects. Additionally, retinol palmitate (RP) and ascorbic acid (AA) were also co-treated with OME to evaluate possible modulatory effects of OME-induced cytogenetic damages. OME was tested at 10, 20 and 40 μg/mL, while RP and AA at 55 μg/mL and 352.2 μg/mL, respectively. Copper sulphate (0.6 μg/mL) and dechlorinated water were used as positive control and negative control, respectively. The results suggest that OME induced genotoxicity and mutagenicity in A. cepa at all tested concentrations. It was noted that cotreatment of OME with the antioxidant vitamins RP and/or AA significantly (p < 0.05) inhibited and/or modulated all toxicogenic damages induced by OME. These observations demonstrate their antigenotoxic, antimutagenic, antitoxic and anticitotoxic effects in A. cepa. This study indicates that application of antioxidants may be useful tools to overcome OME-induced toxic effects.

Topics: Allium; Antioxidants; Ascorbic Acid; Diterpenes; DNA Damage; Mutagenesis; Mutagens; Omeprazole; Plant Extracts; Retinyl Esters; Toxicogenetics; Vitamin A

A new and simple high-performance liquid chromatography method was developed and validated for the simultaneous determination of retinol, retinyl palmitate, β-carotene, α-tocopherol and vitamin C in rat serum treated with Plantago Major L. and 7,12 dimethylbenz[a]anthracene. High-performance liquid chromatography analysis was performed utilizing an Inertsil ODS3 reversed phase column with methanol-tetrahydrofuran-water as mobile phase under gradient conditions, at 1.5 mL min(-1) flow rate and 25 °C. Diode-array detection was at 325, 450, 290 and 270 nm (retinol and retinyl palmitate), β-carotene, α-tocopherol and vitamin C, respectively and runnig time 18 min. The high-performance liquid chromatography assay and extraction procedure proposed are simple, rapid, sensitive and accurate. The method was then applied for the determination of retinol, retinyl palmitate, β-carotene, α-tocopherol and vitamin C in rat serum. Results of this study demonstrated that; at 60th day DMBA-treated group, there was a significant decrease in vitamin levels compared to the levels of control group. A significant increase was observed in vitamin levels of 7,12 dimethylbenz[α]anthracene+Plantago Major L.-treated group compared to the DMBA-treated group. Additionally, the results obtained in the study are found to be in agreement with data reported in the literature.

Topics: 9,10-Dimethyl-1,2-benzanthracene; alpha-Tocopherol; Animals; Ascorbic Acid; beta Carotene; Carcinogens; Chromatography, High Pressure Liquid; Diterpenes; Plant Extracts; Plantago; Rats; Rats, Wistar; Retinyl Esters; Sensitivity and Specificity; Vitamin A

Chronic kidney disease (CKD) may affect excretion and metabolism of vitamins but data for dogs are limited. In this study, blood vitamin levels were investigated in 19 dogs with chronic renal failure. High performance liquid chromatography was used to quantify retinol, retinyl esters, tocopherol, thiamine, riboflavin, pyridoxal-5'-phosphate, ascorbic acid and 25-hydroxycholecalciferol concentrations, whereas cobalamin, folate, biotin and pantothenic acid were measured by microbiological methods. Levels of retinol, retinyl palmitate, ascorbic acid, and vitamins B1, B2 and B6 were increased compared to healthy dogs. Dogs with CKD showed decreased concentrations of 25-hydroxycholecalciferol and folate. Alpha-tocopherol, biotin, pantothenate and cobalamin levels were not significantly different between controls and dogs with CKD. Whether lower vitamin D and folate concentrations in dogs with CKD justify supplementation has to be evaluated in future studies.

Topics: Animals; Ascorbic Acid; Calcifediol; Case-Control Studies; Diterpenes; Dog Diseases; Dogs; Female; Folic Acid; Kidney Failure, Chronic; Male; Retinyl Esters; Riboflavin; Thiamine; Vitamin A; Vitamin B 6; Vitamins

Chemically stable ester derivatives of vitamins A, C and E have become a focus of interest for their role in the satisfactory results in skin aging treatments. Accordingly, the aim of this study was to evaluate the physical and chemical stability of a cosmetic formulation containing 1% retinyl palmitate, ascorbyl tetraisopalmitate and tocopheryl acetate, alone or in combination. In the studies of physical stability, a Brookfield rheometer was used to determine rheological behavior of formulations containing the vitamins. Chemical stability was determined by HPLC on a Shimadzu system with UV detection. Results showed that formulations had pseudoplastic behavior and that vitamins did not alter their apparent viscosity and thixotropy. In the chemical stability studies, first-order reaction equations were used for determinations of the shelf-life of vitamins derivatives considering a remaining concentration of 85%. Combined vitamins in a single formulation had a slightly lower degradation rate as compared to different preparations containing only one of the vitamins. Considering that many cosmetic formulations contain vitamin combinations it is suggested that the present study may contribute to the development of more stable formulations containing liposoluble vitamins.

Topics: Ascorbic Acid; Chemistry, Pharmaceutical; Cosmetics; Diterpenes; Drug Stability; Retinyl Esters; Vitamin A; Vitamin E

It is already known that the photostability of a sunscreen is important for its performance on human skin. On the other hand, there are many formulations besides sunscreens containing combinations of UV-filters and daily use active substances with other claims like hydration and anti-aging effects. Vitamins A, C and E are frequently added in these kinds of products and it is not known if the UV-filters have some influence on the hydration and anti-aging effects of these vitamins on the skin as well as on their stability mainly when photounstable UV-filters like avobenzone and octyl methoxycinnamate are present in the formulation. Thus, the aim of this study was to evaluate the influence of two different UV-filters combinations, a photostable and a photounstable one, on the photostability as well as on the efficacy of a formulation containing vitamin A, C and E derivatives. The formulations that were investigated contained or not (vehicle: formulation 1) a combination of 0.6 % (w/w) vitamin A palmitate (1,700,000 UI/g), 2 % (w/w) vitamin E acetate and 2% (w/w) ascorbyl tetraisopalmitate (formulation 2) supplemented with a photounstable UV filter combination octyl methoxycinnamate (OMC), avobenzone (AVB) and 4-methylbenzilidene camphor (MBC) (formulation 3) or with a photostable UV filter combination OMC, benzophenone-3 (BP-3) and octocrylene (OC) (formulation 4). In the photostability studies, all formulations were spread onto a glass plate and exposed to UVA/UVB irradiation. The filter components and vitamins were quantified by HPLC analysis with detection at 325 and 235 nm and by spectrophotometry. To simulate the effects of these formulations daily use, all of them (formulations 1-4) were applied on the dorsum of hairless mice, which were submitted to a controlled light-dark cycle (and were not irradiated), once a day for 5 days. Transepidermal water loss (TEWL), water content of the stratum corneum and viscoelastic properties of the skin were analyzed by using different non-invasive Biophysics Techniques in order to evaluate hydration and anti-aging effects of these formulations as well as erythema to assess skin irritation. Histopathology, viable epidermal thickness as well as the number of epidermal cell layers were also evaluated. It was observed that both UV filters combinations (photounstable one containing OMC, AVB and MBC and photostable one containing OMC, BP-3 and OC) enhanced vitamin A photostability and F4 was more photostable than F3, in te

Topics: Administration, Cutaneous; alpha-Tocopherol; Animals; Ascorbic Acid; Diterpenes; Drug Stability; Male; Mice; Mice, Hairless; Retinyl Esters; Skin; Sunscreening Agents; Tocopherols; Ultraviolet Rays; Vitamin A; Vitamins; Water

The free radical scavenging properties of retinyl ascorbate (RA-AsA) were determined by monitoring the decomposition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) as a function of time and in comparison with ascorbic acid (AsA), ascorbic acid palmitate (AsA-Pal), retinoic acid (RA), retinol (ROL) and retinol palmitate (Rol-Pal). The rate constant of RA-AsA (mean3+/-SD) was 4.9+/-0.3 M(-1) s(-1), and indicated greater potency as an antioxidant compared to the rest of the test compounds (AsA 3.4+/-0.4 M(-1) s(-1), AsA-Pal, 2.9+/-0.2 M(-1) s(-1), RA 1.4+/-0.3 M(-1) s(-1), ROL 1.3+/-0.1 M(-1) s(-1), Rol-Pal exhibited insignificant activity). The decomposition rate constant of DPPH, 5+/-0.6 x 10(-8) M(-1) s(-1), in ethanol and BHA, 154+/-3 M(-1) s(-1) were both used as control. The compound RA-2-carboxy-2-hydroxy-ethanoate was isolated by prep-TLC and was identified, by 13C and 1HNMR spectroscopy, as the major by-product from the reaction of RA-AsA with DPPH, which was also found to be potent antioxidant, 2.1+/-0.2 M(-1) s(-1). This suggests that oxidation of AsA moiety did not lead to the production of erythrulose species, which could cause deleterious modifications of cellular proteins.

Topics: Administration, Topical; Ascorbic Acid; Biphenyl Compounds; Diterpenes; Free Radical Scavengers; Hydrazines; Picrates; Retinoids; Retinyl Esters; Tretinoin; Vitamin A

Beta-carotene has been shown to exhibit a good radical-trapping antioxidant activity in vitro. We were interested to see if dietary beta-carotene in combination with various intake levels for vitamin A would also inhibit lipid peroxidation.. Sixty male Wistar rats received vitamin A (as retinyl palmitate) for 14 weeks in the diet (40,000, 4000 and 400 IU/kg food). In the last 5 weeks one half of each group received beta-carotene (50 mg/kg food). Lipid peroxidation (induced by 10 microM Fe2+ and 0.2 mM ascorbate) was measured ex vivo in liver microsomes.. The beta-carotene-treated group had similar beta-carotene levels in liver microsomes (3.4 nmol per mg protein) as the other group, irrespective of vitamin A intake. No difference in lipid peroxidation was seen between the groups with different beta-carotene and vitamin A diets.. Beta-carotene is not effective in vitro as antioxidant in liver microsomes of rats fed beta-carotene with various intakes of vitamin A.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Diterpenes; Ferrous Compounds; Glutathione; Lipid Peroxidation; Male; Microsomes, Liver; Rats; Rats, Wistar; Retinyl Esters; Vitamin A

Two groups of weanling male Sprague-Dawley rats fed a diet supplemented with either 0.6 or 6 retinol equivalents/g diet were each separated into three further groups receiving 300 mumol 2,2',4,4',5,5'-hexachlorobiphenyl/kg body weight, 300 mumol 3,3',4,4'-tetrachlorobiphenyl kg/body weight or vehicle only (corn oil). Only the coplanar (3,4)2Cl congener caused a slight reduction in food intake, thymic atrophy and led to a significant decrease in the liver vitamin A storage. The vitamin A lost by the liver was approximately the same in both dietary groups; however an increased renal accumulation of vitamin A was observed in the high vitamin A group. Serum retinol was reduced by (3,4)2Cl treatment but remained unchanged by (2,4,5)2Cl exposure. Total amounts of ascorbic acid and its oxidation products were increased in the liver and in the kidney by both xenobiotics while niacin and thiamine concentrations were lowered by (3,4)2Cl only. Microsomes from vitamin A-deficient rats exhibited a marked decrease in the anisotropy parameter. After (2,4,5)2Cl exposure, an increase in membrane fluidity was observed linked to a decrease in cholesterol/phospholipid (C/P) ratio. Treatment with (3,4)2Cl caused a significant decrease in the index of fluorescence polarization only in the low vitamin A group even if the C/P ratio was enhanced in both dietary groups. This study shows that the polychlorinated biphenyl with the 3-methylcholanthrene-type pattern of induction of cytochrome P-450 has more profound effects on B group vitamins and particularly vitamin A homeostasis than does the phenobarbital-type inducer. Moreover, this situation, which has been found to be similar to that in vitamin A deficiency, is not ameliorated by a high dietary vitamin A intake.

Topics: Animals; Ascorbic Acid; Diet; Diterpenes; Kidney; Liver; Male; Microsomes, Liver; Polychlorinated Biphenyls; Rats; Rats, Sprague-Dawley; Retinyl Esters; Vitamin A

Vitamin A (retinol) and some of its analogs exhibited varying degrees of inhibition on induced iron and ascorbic acid lipid peroxidation of rat brain mitochondria. Malonyldialdehyde production was used as an index of the extent of in vitro lipid peroxidation. The fat-soluble vitamins retinol, retinol acetate, retinoic acid, retinol palmitate, and retinal at concentrations between 0.1 and 10.0 mmol/L inhibited brain lipid peroxidation. Retinol and retinol acetate were the most effective inhibitors. It is concluded from this study that retinol and its analogs can be considered as potential antioxidant factors, more potent than some of the well-known antioxidants such as alpha-tocopherol and butylated hydroxytoluene.

Topics: Animals; Ascorbic Acid; Brain; Diterpenes; Ferrous Compounds; Free Radicals; Lipid Peroxidation; Male; Malondialdehyde; Mitochondria; Rats; Rats, Inbred Strains; Retinaldehyde; Retinyl Esters; Tretinoin; Vitamin A

Rats were maintained on a vitamin E free diet containing 20% safflower oil for a period of 12 weeks at two dietary protein levels, 20% and 10% casein. Enhanced in vitro tissue lipid peroxidation and lysis of erythrocytes were noticed at both the protein levels. A reduction in body mass and tissue weights were observed in both the protein groups but more so at 20% protein level. Feeding of retinyl palmitate (100 000 IU/100 g body weight) for 4 consecutive days to -E rats inhibited liver and kidney in vitro lipid peroxidation. Ascorbic acid (150 mg/100 g body weight) given orally for 5 days to -E rats inhibited liver brain and kidney in vitro peroxidation. Lysis of erythrocytes from -E rats was further increased by dosing with both the vitamins "A" and "C", the latter being more effective. The stromal enzymes acetyl choline esterase and ATPase were lowered, following the hemolysis profile of the erythrocytes from the different groups. Glutathione content of erythrocytes were unaffected except in -E +C group. In all groups the higher protein level (20%) produced greater lysis as compared to 10% level. It is concluded that 20% protein is more injurious in vitamin E deficiency simultaneously made hypervitaminosis A or C.

Topics: Animals; Ascorbic Acid; Dietary Fats; Dietary Proteins; Diterpenes; Hemolysis; Lipid Peroxides; Male; Oxidation-Reduction; Rats; Retinyl Esters; Vitamin A; Vitamin E Deficiency

Topics: Animals; Ascorbic Acid; Diterpenes; Dust; Glass; Lung; Lung Neoplasms; Male; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Retinyl Esters; Vitamin A