A new water-soluble oral vitamin E formulation in cystic fibrosis (CF) children

ABSTRACT Burkholderia cenocepacia is an opportunistic Gram-negative bacterium that causes serious respiratory infections in patients with cystic fibrosis. Recently, we discovered that B. cenocepacia produces the extracellular bacterial lipocalin protein BcnA upon exposure to sublethal concentrations of bactericidal antibiotics. BcnA captures a range of antibiotics outside bacterial cells, providing a global extracellular mechanism of antimicrobial resistance. In this study, we investigated water-soluble and liposoluble forms of vitamin E as inhibitors of antibiotic binding by BcnA. Our results demonstrate that in vitro, both vitamin E forms bind strongly to BcnA and contribute to reduce the MICs of norfloxacin (a fluoroquinolone) and ceftazidime (a β-lactam), both of them used as model molecules representing two different chemical classes of antibiotics. Expression of BcnA was required for the adjuvant effect of vitamin E. These results were replicated in vivo using the Galleria mellonella larva infection model whereby vitamin E treatment, in combination with norfloxacin, significantly increased larva survival upon infection in a BcnA-dependent manner. Together, our data suggest that vitamin E can be used to increase killing by bactericidal antibiotics through interference with lipocalin binding. IMPORTANCE Bacteria exposed to stress mediated by sublethal antibiotic concentrations respond by adaptive mechanisms leading to an overall increase of antibiotic resistance. One of these mechanisms involves the release of bacterial proteins called lipocalins, which have the ability to sequester antibiotics in the extracellular space before they reach bacterial cells. We speculated that interfering with lipocalin-mediated antibiotic binding could enhance the efficacy of antibiotics to kill bacteria. In this work, we report that when combined with bactericidal antibiotics, vitamin E contributes to enhance bacterial killing both in vitro and in vivo. This adjuvant effect of vitamin E requires the presence of BcnA, a bacterial lipocalin produced by the cystic fibrosis pathogen Burkholderia cenocepacia. Since most bacteria produce lipocalins like BcnA, we propose that our findings could be translated into making novel antibiotic adjuvants to potentiate bacterial killing by existing antibiotics.

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CFTR Modulator Therapy with Lumacaftor/Ivacaftor Alters Plasma Concentrations of Lipid-Soluble Vitamins A and E in Patients with Cystic Fibrosis

Antioxidants ◽

10.3390/antiox10030483 ◽

2021 ◽

Vol 10 (3) ◽

pp. 483

Author(s):

Olaf Sommerburg ◽

Susanne Hämmerling ◽

S. Philipp Schneider ◽

Jürgen Okun ◽

Claus-Dieter Langhans ◽

...

Keyword(s):

Cystic Fibrosis ◽

Vitamin E ◽

Vitamin A ◽

Clinical Chemistry ◽

Pancreatic Insufficiency ◽

Plasma Concentrations ◽

Plasma Vitamin ◽

Hypervitaminosis A ◽

Cholesterol Ratio ◽

Fat Soluble Vitamins

Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. However, the effects of LUM/IVA on plasma concentration of the lipid soluble vitamins A and E remain unknown. Objectives: To investigate the course of plasma vitamin A and E in patients with CF under LUM/IVA therapy. Methods: Data from annual follow-up examinations of patients with CF were obtained to assess clinical outcomes including pulmonary function status, body mass index (BMI), and clinical chemistry as well as fat-soluble vitamins in Phe508del-homozygous CF patients before initiation and during LUM/IVA therapy. Results: Patients with CF receiving LUM/IVA improved substantially, including improvement in pulmonary inflammation, associated with a decrease in blood immunoglobulin G (IgG) from 9.4 to 8.2 g/L after two years (p < 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 µmol/L (p < 0.05), however, levels above the upper limit of normal were not detected in any of the patients. In contrast, plasma vitamin E as vitamin E/cholesterol ratio decreased moderately over the same time from 6.2 to 5.5 µmol/L (p < 0.01). Conclusions: CFTR modulator therapy with LUM/IVA alters concentrations of vitamins A and vitamin E in plasma. The increase of vitamin A must be monitored critically to avoid hypervitaminosis A in patients with CF.

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Inhibition of γ-Radiation Induced DNA Damage in Plasmid pBR322 by TMG, a Water-soluble Derivative of Vitamin E

Journal of Radiation Research ◽

10.1269/jrr.43.153 ◽

2002 ◽

Vol 43 (2) ◽

pp. 153-153 ◽

Cited By ~ 35

Author(s):

REMA RAJAGOPALAN ◽

KHALIDA WANI ◽

NAGARAJ G. HUILGOL ◽

TSUTOMU V. KAGIYA ◽

CHERUPALLY K. KRISHNAN NAIR

Keyword(s):

Dna Damage ◽

Vitamin E ◽

Water Soluble ◽

Plasmid Pbr322 ◽

Γ Radiation ◽

Radiation Induced

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Analysis of biochemical composition and antioxidant properties of nuts sold in the consumer marke

Proceedings of the Voronezh State University of Engineering Technologies ◽

10.20914/2310-1202-2020-2-124-130 ◽

2020 ◽

Vol 82 (2) ◽

pp. 124-130

Author(s):

L. P. Nilova ◽

S. M. Malyutenkova

Keyword(s):

Fatty Acids ◽

Vitamin E ◽

Phenolic Compounds ◽

Biochemical Composition ◽

Unsaturated Fatty Acids ◽

Antioxidant Properties ◽

Water Soluble ◽

Total Phenolic ◽

Consumer Market ◽

Triton X

The results of studies of the biochemical composition and antioxidant properties of nuts sold in the consumer market of St. Petersburg were presented in the work. The objects of research were kernels of nuts: sweet almonds, hazelnuts, cashews, walnuts. Total Soxhlet lipids, fatty acid composition, vitamin E, fractional composition of tocopherols and phytosterols, total phenolic compounds and flavonoids, antioxidant activity by FRAP with ferric chloride, o-phenanthroline and Triton X 100 were determined in nuts. Nuts varied in lipid content (42.6–65.4%) with a predominance of unsaturated fatty acids from 80.4 to 92.4 relative%. Oleic acid prevailed in the fatty acids of almonds, hazelnuts and cashews, while linoleic acid prevailed in walnuts. Walnuts contained the highest amount of polyunsaturated fatty acids. The antioxidant properties of nuts were formed by a complex of water and fat-soluble antioxidants. Fat-soluble antioxidants included vitamin E with a predominance of ?-tocopherol in the kernels of sweet almonds and hazelnuts, ?-tocopherol - in walnuts and cashews. Only sweet almond kernels contained all the tocopherol fractions. ?- and ?-tocopherols were absent in hazelnut lipids, while ?-tocopherols were absent in cashews and walnuts. ?-sitosterol, campesterol and stigmasterol with a predominance of ?-sitosterol were identified in the composition of phytosterols in all nut kernels. Water-soluble antioxidants are mainly represented by phenolic compounds, the amount of which varies widely depending on the type of nuts: cashews

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Effects of indirect exposure of mice pups to endosulfan via their dams during gestation and lactation periods and the ameliorative effect of vitamin E

Human & Experimental Toxicology ◽

10.1177/0960327113512343 ◽

2013 ◽

Vol 33 (9) ◽

pp. 911-927 ◽

Cited By ~ 6

Author(s):

SA Mansour ◽

DA Mohamed ◽

L Gamet-Payrastre

Keyword(s):

Vitamin E ◽

Low Dose ◽

Dietary Exposure ◽

Oral Vitamin ◽

Blood Samples ◽

Oral Supplementation ◽

Maximum Value ◽

Indirect Exposure ◽

Ameliorative Effect ◽

Butyryl Cholinesterase

During gestation and lactation, the experimental mice dams received one of the following treatments: (a) diet free of pesticide; (b) diet enriched with endosulfan (END); 30.0 µg kg−1; (c) diet free of pesticide + oral vitamin E (α-tocopherol; 200 mg kg−1 per mouse); and (d) diet enriched with END (30.0 µg kg−1) + oral vitamin E (200 mg kg−1 per mouse). At weaning, pups and dams were killed, and selected organs as well as blood samples were collected for analyses. Compared with the control results, END induced alteration in a number of biochemical and histopathological parameters either in the dams or their offspring. The ameliorative effect of vitamin E to superoxide dismutase based on the “ameliorative index (AI)” for mothers and pups was 0.84 and 0.72, respectively. The AI for malondialdehyde reached a maximum value of nearly equal to 1.0 for dams or pups. For butyryl cholinesterase, the AI was 0.90 and 0.94 for dams and pups, respectively. In conclusion, a dietary exposure during gestation and lactation to low dose of END caused significant changes in the mother but also in the weaned animals that had not been directly exposed to this pesticide. These biological and histological alterations could be reversed to a great extent by oral supplementation of vitamin E.

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Retrolental Fibroplasia and Vitamin E in the Preterm Infant—Comparison of Oral Versus Intramuscular:Oral Administration

PEDIATRICS ◽

10.1542/peds.73.2.238 ◽

1984 ◽

Vol 73 (2) ◽

pp. 238-249

Author(s):

Helen M. Hittner ◽

Michael E. Speer ◽

Arnold J. Rudolph ◽

Cindy Blifeld ◽

Prabhujeet Chadda ◽

...

Keyword(s):

Vitamin E ◽

Very Low Birth Weight ◽

Plasma Vitamin ◽

Oral Vitamin ◽

Low Birth Weight Infants ◽

Retrolental Fibroplasia ◽

Intramuscular Injections ◽

Significant Difference ◽

Plasma Vitamin E ◽

Vitamin E Supplementation

To evaluate the efficacy of four early intramuscular injections of vitamin E given in addition to continuous minimal oral vitamin E supplementation, 168 very low-birth-weight infants (≤1,500 g) have enrolled in a randomized, double-masked, clinical study. All infants received vitamin E orally, 100 mg/kg/d. In addition, on days 1, 2, 4, and 6, seventy-nine infants received vitamin E intramuscularly, 15, 10, 10, and 10 mg/kg, respectively. On the same days, 89 control infants received placebo intramuscular injections. Multivariate analysis of the 135 infants who survived ≥10 weeks showed no significant difference in the development of severe retrolental fibroplasia between these two supplementation schedules (P = .86). Plasma vitamin E levels never exceeded a mean of 3.3 mg/100 mL, and no toxicity was observed. Ultrastructural analyses of seven pairs of whole eye donations from infants receiving IM vitamin E demonstrated identical kinetics of gap junction formation between adjacent spindle cells as compared with 13 pairs of whole eye donations from control infants (P > .3). Therefore, oral vitamin E supplementation affords retinal protection against the development of severe retrolental fibroplasia when initiated on the first day of life and maintained continuously until retinal vascularization is complete.

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Water- and Fat-Soluble Antioxidants in Human Seminal Plasma and Serum of Fertile Males

Antioxidants ◽

10.3390/antiox8040096 ◽

2019 ◽

Vol 8 (4) ◽

pp. 96 ◽

Cited By ~ 7

Author(s):

Giacomo Lazzarino ◽

Ilaria Listorti ◽

Gabriele Bilotta ◽

Talia Capozzolo ◽

Angela Amorini ◽

...

Keyword(s):

Ascorbic Acid ◽

Uric Acid ◽

Vitamin E ◽

Vitamin C ◽

Seminal Plasma ◽

Sperm Count ◽

Venous Blood ◽

Water Soluble ◽

Human Seminal Plasma ◽

Serum Ratio

Reactive oxygen species (ROS) are physiologically involved in functions like sperm maturation, capacitation and acrosome reaction, but their excess is involved in male infertility. Antioxidants in seminal plasma (SP) are an important factor balancing physiologic and harmful ROS activities. In this study, we determined and compared the full profiles of the water- and fat-soluble antioxidants in SP and serum of 15 healthy fertile subjects (ranging between the ages of 35 and 42 years). Ejaculates were obtained after 2–5 days of sexual abstinence. After liquefaction and withdrawal of an aliquot for the sperm count, samples were centrifuged to obtain SP. Thirty min after semen donation, a venous blood sample was collected from each subject. Donors with lower SP concentrations of ascorbic acid (n = 5) or α-tocopherol (n = 5) received a 4 week oral administration of either vitamin C (100 mg/day) or vitamin E (30 mg/day). They were then re-assayed to determine the SP and serum levels of ascorbic acid and α-tocopherol. SP and serum samples were properly processed and analyzed by HPLC methods suitable to determine water (ascorbic acid, glutathione (GSH) and uric acid) and fat-soluble (all-trans-retinoic acid, all-trans-retinol, α-tocopherol, carotenoids and coenzyme Q10) antioxidants. Data demonstrate that only ascorbic acid is higher in SP than in serum (SP/serum ratio = 4.97 ± 0.88). The other water-soluble antioxidants are equally distributed in the two fluids (GSH SP/serum ratio = 1.14 ± 0.34; uric acid SP/serum ratio = 0.82 ± 0.12). All fat-soluble antioxidants are about 10 times less concentrated in SP than in serum. In donors treated with vitamin C or vitamin E, ascorbic acid and α-tocopherol significantly increased in both fluids. However, the SP/serum ratio of ascorbic acid was 4.15 ± 0.45 before and 3.27 ± 0.39 after treatment, whilst those of α-tocopherol were 0.11 ± 0.03 before and 0.10 ± 0.02 after treatment. The results of this study, by showing the peculiar composition in water- and fat-soluble antioxidants SP, indicate that it is likely that still-unknown mechanisms allow ascorbic acid accumulation in SP against a concentration gradient. SP mainly relies its defenses on water- rather than fat-soluble antioxidants and on the mechanisms ensuring their transfer from serum.

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Improvement of enzyme carbon paste-based biosensor using carbon nanotubes for determination of water-soluble analogue of vitamin E

Chemical Papers ◽

10.2478/s11696-014-0608-9 ◽

2015 ◽

Vol 69 (1) ◽

Cited By ~ 3

Author(s):

Milan Sýs ◽

Radovan Metelka ◽

Tomáš Mikysek ◽

Karel Vytřas

Keyword(s):

Carbon Nanotubes ◽

Vitamin E ◽

Electrochemical Techniques ◽

Enzymatic Reaction ◽

Direct Determination ◽

Water Soluble ◽

Trolox Equivalent Antioxidant Capacity ◽

Total Phenolic ◽

Antioxidant Power

AbstractThe catalytic oxidation of a synthetic water-soluble analogue of vitamin E (α-tocopherol, Trolox) by tyrosinase enzyme in the presence of molecular oxygen was studied using electrochemical techniques. This specific enzymatic reaction was exploited for the preparation of a biosensor based on the amperometric reduction of the electroactive product (α-tocoquinone) formed. An electroactive surface of the transducers used was covered with a thin conductive layer of Nafion containing tyrosinase. Significant progress in sensitivity towards polyphenolic compounds such as Trolox was achieved at CPE with carbon nanotubes immobilised on its surface (CPE/CNTs) as electric transducers. The biosensor so developed can be used for the direct determination of total phenolic content (TPC). This important nutrition value can be expressed as the mass equivalent of Trolox, i.e. Trolox equivalent antioxidant capacity (TEAC), which could be used as an alternative to the evaluations currently used based on spectrophotometric methods such as total radical-trapping antioxidant parameter (TRAP), ferric reducing-antioxidant power (FRAP) or 1,1-diphenyl-2-picrylhydrazyl spectrometric assay (DPPH). The effects of the enzyme amount in the Nafion layer (3.0 μg), the influence of the nanoparticles present, the optimal pH value suitable for enzymatic activity (7.0), and the kinetics of enzymatic and electrochemical reactions were studied using cyclic voltammetry (CV). The determination of optimal conditions for amperometry in batch configuration (working potential, speed of stirring, volume of sample, calibration curve, etc.) was not a target of this electrochemical study.

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