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Toxins Jan 2023Background: Panton−Valentine Leukocidin sustains a strong cytotoxic activity, targeting immune cells and, consequently, perforating the plasma membrane and inducing...
Background: Panton−Valentine Leukocidin sustains a strong cytotoxic activity, targeting immune cells and, consequently, perforating the plasma membrane and inducing cell death. The present study is aimed to examine the individual effect of ascorbic acid and nicotinamide on PVL cytotoxicity ex vivo, as well as their effect on granulocytes viability when treated with PVL. Materials and Methods: The PVL cytotoxicity assay was performed in triplicates using the commercial Cytotoxicity Detection Kit PLUS (LDH). LDH release was measured to determine cell damage and cell viability was measured via flow cytometry. Results and discussion: A clear reduction in PVL cytotoxicity was demonstrated (p < 0.001). Treatment with ascorbic acid at 5 mg/mL has shown a 3-fold reduction in PVL cytotoxicity; likewise, nicotinamide illustrated a 4-fold reduction in PVL cytotoxicity. Moreover, granulocytes’ viability after PVL treatment was maintained when incubated with 5 mg/mL of ascorbic acid and nicotinamide. Conclusions: our findings illustrated that ascorbic acid and nicotinamide exhibit an inhibitory effect on PVL cytotoxicity and promote cell viability, as the cytotoxic effect of the toxin is postulated to be neutralized by antioxidant incubation. Further investigations are needed to assess whether these antioxidants may be viable options in PVL cytotoxicity attenuation in PVL-associated diseases.
Topics: Humans; Ascorbic Acid; Bacterial Toxins; Exotoxins; Leukocidins; Niacinamide
PubMed: 36668859
DOI: 10.3390/toxins15010038 -
Biomolecules Jan 2020Cancer remains one of the most feared and dreaded diseases in this era of modern medicine, claiming the lives of many, and affecting the quality of life of several... (Review)
Review
Cancer remains one of the most feared and dreaded diseases in this era of modern medicine, claiming the lives of many, and affecting the quality of life of several others around the globe despite major advances in the diagnosis, treatment, palliative care and the immense resources invested into cancer research. While research in cancer has largely focused on the neoplasm/tumor and the cancerous cells that make up the tumor, more recently, the existence, proliferation, differentiation, migration and invasion of cancer stem cells (CSCs) and the role that CSCs play in tumor initiation, progression, metastasis, drug resistance and relapse/recurrence of the disease has gained widespread interest in cancer research. Although the conventional therapeutic approaches such as surgery, chemotherapy and radiation therapy are effective cancer treatments, very often these treatment modalities fail to target the CSCs, which then later become the source of disease recurrence. A majority of the anti-cancer agents target rapidly dividing cancer cells and normal cells and hence, have side effects that are not expected. Targeting CSCs remains a challenge due to their deviant nature with a low proliferation rate and increased drug resistance mechanism. Ascorbic acid/Vitamin C (Vit.C), a potent antioxidant, is a cofactor for several biosynthetic and gene regulatory enzymes and a vital contributor to immune defense of the body, and was found to be deficient in patients with advanced stages of cancer. Vit.C has gained importance in the treatment of cancer due to its ability to modulate the redox status of the cell and influence epigenetic modifications and significant roles in HIF1α signaling. Studies have reported that intravenous administration of Vit.C at pharmacological doses selectively kills tumor cells and targets CSCs when administered along with chemotherapeutic drugs. In the current article, we provide an in-depth review of how Vit.C plays an important role in targeting CSCs and its possible use as an adjuvant, neoadjuvant or co-treatment in the treatment of cancers.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Cell Differentiation; Cell Transformation, Neoplastic; Combined Modality Therapy; Drug Resistance, Neoplasm; Humans; Neoplasms; Neoplastic Stem Cells; Signal Transduction
PubMed: 31947879
DOI: 10.3390/biom10010079 -
International Journal of Molecular... Jun 2020Ascorbic acid (AA) is a general antioxidant used in aqueous pharmaceutical formulations. However, in aqueous solutions, AA is unstable and easily oxidized when exposed...
Ascorbic acid (AA) is a general antioxidant used in aqueous pharmaceutical formulations. However, in aqueous solutions, AA is unstable and easily oxidized when exposed to air, light and/or heat. Cyclodextrins are well known for their ability to form inclusion complexes with various compounds to improve their solubility and stability. Previous studies demonstrate that cyclodextrins preserve the antioxidant capacity of AA but data for γ-cyclodextrin (γCD) have not been reported. Poly(vinyl alcohol) (PVA) is a hydrophilic polymer widely used as a drug matrix in various pharmaceutical fields, but its application for drug stabilization is limited. This study aimed to investigate the protective ability of γCD on AA through the formation of ternary complexes with PVA. Binary (i.e., AA/γCD, AA/PVA and γCD/PVA) and ternary (i.e., AA/γCD/PVA) complexes were first confirmed. It was reported that those complexes were formed through interactions between the heterocyclic ring of AA, hydroxyl group of PVA and hydrophobic cavity of γCD. The hydrodynamic diameter of complexes was then studied. It was found that the diameter of γCD/PVA complexes increased with respect to the concentration of γCD. Higher γCD concentrations also resulted in increasing hydrodynamic diameters of the ternary complex. The presence of AA in ternary complexes interfered with the aggregation tendency of γCD/PVA binary complexes. Furthermore, the antioxidant capacity of AA in binary and ternary complexes was investigated. It was found that the presence of γCD preserved the antioxidant activity of AA, whereas PVA showed a contrasting effect. The influence of γCD and PVA concentration on antioxidant capacity was then studied through central composite design (CCD). Even though the concentration of γCD significantly affected the inhibition efficiency of the ternary complex, the insignificant influence of PVA could not be ignored. A promising protective ternary complex should consist of an optimized concentration of PVA and a high concentration of γCD.
Topics: Antioxidants; Ascorbic Acid; Drug Compounding; Drug Stability; Molecular Structure; Polyvinyl Alcohol; Spectroscopy, Fourier Transform Infrared; gamma-Cyclodextrins
PubMed: 32575742
DOI: 10.3390/ijms21124399 -
Chemical Research in Toxicology Oct 2020Vitamin C (ascorbic acid) is a water-soluble antioxidant and a cofactor for a large number of enzymes. It is present in all tissues and especially abundant in corneal... (Review)
Review
Vitamin C (ascorbic acid) is a water-soluble antioxidant and a cofactor for a large number of enzymes. It is present in all tissues and especially abundant in corneal epithelium, stem cells, and neurons. Although similar to thiols in its ability to react with many reactive oxygen species (ROS), ascorbate is much better (>100× faster) than glutathione at scavenging of primary ROS (superoxide radical and singlet oxygen). Ascorbate appears to be especially important for elimination of O in the nucleus which contains little or no SOD activity. Cofactor functions of ascorbate involve the maintenance of activity of Fe(II)/2-oxoglutarate-dependent dioxygenases via reduction of Fe(III). The most prominent activity of ascorbate-dependent dioxygenases in the cytoplasm is hydroxylation of prolines in proteins involved in the formation of extracellular matrix and regulation of metabolism and hypoxia responses. In the nucleus, ascorbate is important for oxidative demethylation of 5-methylcytosine in DNA (by TET proteins) and removal of methyl groups from histone lysines (by JmjC demethylases). Differentiation and other cellular reprograming processes involving DNA demethylation are especially sensitive to ascorbate insufficiency. High doses of vitamin C alone or in combinations with drugs produced cancer-suppressive effects which involved redox, immune, and epigenetic mechanisms. Solutions to vitamin C deficiency in cultured cells are discussed to improve the physiological relevance of models. An abundance of vitamin C in rodents limits their ability to fully recapitulate human sensitivity to adverse health effects of malnutrition and xenobiotics, including neurotoxicity, lung injury, and intergenerational and other epigenetic effects.
Topics: Animals; Ascorbic Acid; Cell Nucleus; Cytoplasm; DNA; Humans
PubMed: 33001635
DOI: 10.1021/acs.chemrestox.0c00348 -
Cell Reports Dec 2020Plasma cells provide high-affinity antibodies against invading pathogens. Although transcriptional and epigenetic mechanisms have been extensively studied for plasma...
Plasma cells provide high-affinity antibodies against invading pathogens. Although transcriptional and epigenetic mechanisms have been extensively studied for plasma cell differentiation, how these mechanisms respond to environmental cues remains largely unexplored. In this study, we show that ascorbic acid (vitamin C), an essential nutrient, is able to promote plasma cell differentiation and humoral immune response by enhancing TET2/3-mediated DNA demethylation. Ascorbic acid treatment during B cell activation has persistent effects on later plasma cell differentiation by predisposing germinal center B cells toward the plasma cell lineage. Conversely, ascorbic acid deficiency in vivo blocks plasma cell differentiation and attenuates the humoral immune response following antigen immunization. We further demonstrate that such effects of ascorbic acid on plasma cell differentiation require DNA methylcytosine oxidases TET2 and TET3. Our study thus reveals a previously uncharacterized link between essential nutrients and epigenetic regulation of plasma cell differentiation and humoral immune response.
Topics: Animals; Ascorbic Acid; DNA Demethylation; DNA-Binding Proteins; Dioxygenases; Humans; Mice; Plasma
PubMed: 33264617
DOI: 10.1016/j.celrep.2020.108452 -
Drug Delivery Dec 2021l-Ascorbic acid (LAA) is considered a powerful antioxidant that protects skin from premature aging. Maintaining the stability of vitamin C remains the biggest challenge... (Comparative Study)
Comparative Study Randomized Controlled Trial
l-Ascorbic acid (LAA) is considered a powerful antioxidant that protects skin from premature aging. Maintaining the stability of vitamin C remains the biggest challenge in cosmeceuticals. Our main aim is the entrapment of high dose of vitamin C in spanlastic vesicles to provide maximum stability and efficacy. LAA-loaded spanlastics were prepared by ethanol injection method and were characterized for entrapment efficiency (EE%), particles size (PS), polydispersity index (PDI), zeta potential, deformability index (DI) and skin permeation. Selected spanlastics formula composed of span 60 and tween 60 (5:1) showed highest EE% of 89.77 ± 3.61% (w/w), high deformability of 11.13 ± 1.145 as well as good physical and chemical stability for 6 months. Improved drug penetration into stratum corneum (SC) was obtained from spanlastics compared to topical LAA solution. Quantitative real time PCR revealed that MMP2 and MMP9 levels were significantly suppressed in response to LAA spanlastics treated rats by 30.4% and 65.3%, respectively, when compared to the control group after exposure to UV irradiation. Results were confirmed by western blot analysis. Histopathological study of rat skin after UV irradiation revealed that application of LAA-loaded spanlastics provided the highest skin protection compared to UVB and LAA solution treated group which was evident by the normal thick epidermal morphology and the densely arranged dermal collagen fibers. LAA-loaded spanlastics successfully improved LAA stability, skin permeation and antioxidant protection against skin photodamage.
Topics: Administration, Cutaneous; Animals; Antioxidants; Ascorbic Acid; Drug Delivery Systems; Drug Stability; Drug Storage; Female; Humans; Male; Particle Size; Rats; Skin; Skin Absorption; Ultraviolet Rays
PubMed: 33620008
DOI: 10.1080/10717544.2021.1886377 -
ACS Applied Bio Materials Dec 2023This study presents the successful development of printable-microencapsulated ascorbic acid (AA) for personalized topical delivery using laser printing technology. Rice...
This study presents the successful development of printable-microencapsulated ascorbic acid (AA) for personalized topical delivery using laser printing technology. Rice flour with a 10% AA content was selected as an encapsulation material. Hydrophobic nanosilica was used to create negative electrostatic charges on the microencapsulated surfaces via a high-speed mixture. This process facilitated the microencapsulated AA fabrication using a commercial laser printer and produced a well-patterned design with some minor print defects, such as banding and scattering. The amount of encapsulated AA per area was 0.28 mg/cm, and the RGB color code was 0,0,0. An emulsion carrier system comprising pentylene glycol (P5G) or diethylene glycol monoethyl ether (DEGEE), Tween 20, oleic acid, and deionized (DI) water at a ratio of 20:30:30:20 was developed to enhance AA transmission into the skin. The Franz diffusion cell technique was used to investigate topical absorption on Strat-M membranes using P5G and DEGEE as enhancers. The steady-state fluxes were 8.40 (±0.64) and 10.04 (±0.58) μg/h/cm for P5G and DEGEE, respectively. Cytotoxicity tests conducted on fibroblast cells revealed low cytotoxicity for the encapsulation products and carriers.
Topics: Ascorbic Acid; Skin
PubMed: 37981740
DOI: 10.1021/acsabm.3c00648 -
Integrative Cancer Therapies Mar 2005The effect of ascorbic acid on cancer has been a subject of great controversy. This is a follow-up review of the 1979 article by Cameron, Pauling, and Leibovitz... (Review)
Review
The effect of ascorbic acid on cancer has been a subject of great controversy. This is a follow-up review of the 1979 article by Cameron, Pauling, and Leibovitz published in Cancer Research. In this updated version, the authors address general aspects of ascorbic acid and cancer that have been presented before, while reviewing, analyzing, and updating new existing literature on the subject. In addition, they present and discuss their own mechanistic hypothesis on the effect of ascorbic acid on the cancer cell. The objective of this review is to provide an updated scientific basis for the use of ascorbic acid, especially intravenously as adjuvant treatment in pharmacological nutritional oncology.
Topics: Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Humans; Infusions, Intravenous; Neoplasms; Pain; Palliative Care
PubMed: 15695476
DOI: 10.1177/1534735404273861 -
Integrative Cancer Therapies Jul 2014Intravenous vitamin C (IVC) is a contentious adjunctive cancer therapy, widely used in naturopathic and integrative oncology settings. We conducted a systematic review... (Review)
Review
BACKGROUND
Intravenous vitamin C (IVC) is a contentious adjunctive cancer therapy, widely used in naturopathic and integrative oncology settings. We conducted a systematic review of human interventional and observational studies assessing IVC for use in cancer patients.
METHODS
We searched MEDLINE, EMBASE, The Cochrane Library, CINAHL, and AMED from inception to April 2013 for human studies examining the safety, effectiveness, or pharmacokinetics of IVC use in cancer patients.
RESULTS
Of 897 records, a total of 39 reports of 37 studies were included: 2 randomized controlled trials (RCTs), 15 uncontrolled trials, 6 observational studies, and 14 case reports. IVC dosing ranged from 1 g to more than 200 g ascorbic acid per infusion, typically administered 2 to 3 times weekly. IVC does not appear to increase toxicity or interfere with antitumor effects of gemcitabine/erlotinib therapy or paclitaxel and carboplatin. Based on 1 RCT and data from uncontrolled human trials, IVC may improve time to relapse and possibly enhance reductions in tumor mass and improve survival in combination with chemotherapy. IVC may improve quality of life, physical function, and toxicities associated with chemotherapy, including fatigue, nausea, insomnia, constipation, and depression. Case reports document several instances of tumor regression and long-term disease-free survival associated with use of IVC.
CONCLUSION
There is limited high-quality clinical evidence on the safety and effectiveness of IVC. The existing evidence is preliminary and cannot be considered conclusive but is suggestive of a good safety profile and potentially important antitumor activity; however, more rigorous evidence is needed to conclusively demonstrate these effects. IVC may improve the quality of life and symptom severity of patients with cancer, and several cases of cancer remission have been reported. Well-designed, controlled studies of IVC therapy are needed.
Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Humans; Infusions, Intravenous; Neoplasms; Quality of Life; Survival Rate
PubMed: 24867961
DOI: 10.1177/1534735414534463 -
Molecules (Basel, Switzerland) Apr 2021The aim of the present study was to determine the influence of the winemaking process on the antioxidant potential and content of phenolic compounds and L-ascorbic acid...
The aim of the present study was to determine the influence of the winemaking process on the antioxidant potential and content of phenolic compounds and L-ascorbic acid in wines from the fruits of . The results obtained in this study clearly indicate that the fruits of the are a desirable raw material for the production of fruit wine. The parameters of the technological process of producing wines from rose fruits had a diversified influence on the tested quality characteristics. Aged wines contained phenolics levels of 473-958 mg/100 mL GAE. The final concentrations of ascorbic acid ranged from 61 to 155 mg/100 mL for the different variants of the wine. Wines revealed high antioxidant activity in assay with DPPH. On the basis of the obtained results, it can be assumed that all the applied variants of the winemaking process are suitable for rose fruit wine. Each variant ensured at least the stability of the antioxidant capacity.
Topics: Antioxidants; Ascorbic Acid; Chemical Phenomena; Fermentation; Free Radical Scavengers; Fruit; Phytochemicals; Polyphenols; Rosa; Wine
PubMed: 33924795
DOI: 10.3390/molecules26092561