BACKGROUND: Disorders of antioxidant balance are considered to be involved in the toxicity associated with radiotherapy or chemotherapy. PATIENTS AND METHODS: Serum alpha-tocopherol and retinol were determined, by high performance liquid chromatography, before and during therapy with a combination of paclitaxel and carboplatin in 28 patients with breast and ovarian cancer. Serum neopterin and cholesterol were measured using a radioimmunoassay and enzymatic colorimetric method, respectively. RESULTS: Compared to pretreatment concentrations, a significant increase was observed in serum alpha-tocopherol and retinol concentrations during therapy that was associated with decreased serum neopterin concentrations. Serum alpha-tocopherol concentrations were significantly higher during therapy in patients who did not experience serious toxicity. CONCLUSION: An increase in alpha-tocopherol and retinol during therapy with combination paclitaxel/carboplatin may be explained by inhibition of systemic immune activation secondary to control of the tumor with effective chemotherapy. Lower alpha-tocopherol concentrations were associated with the toxicity of therapy.
- MeSH
- alpha-Tocopherol blood MeSH
- Adult MeSH
- Carboplatin administration & dosage MeSH
- Middle Aged MeSH
- Humans MeSH
- Breast Neoplasms blood drug therapy MeSH
- Ovarian Neoplasms blood drug therapy MeSH
- Neopterin blood MeSH
- Paclitaxel administration & dosage MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Aged MeSH
- Vitamin A blood MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- alpha-Tocopherol MeSH
- Carboplatin MeSH
- Neopterin MeSH
- Paclitaxel MeSH
- Vitamin A MeSH
Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal toxicity of anticancer therapy. We have assessed intestinal permeability (by measuring absorption of lactulose, mannitol, and xylose), vitamin A absorption and serum alpha-tocopherol in patients with non-small cell lung carcinoma or head and neck carcinomas treated with gefitinib. Lactulose, mannitol and xylose were determined by capillary gas chromatography, and retinol, alpha-tocopherol, retinyl stearate and retinyl palmitate were determined by high-performance liquid chromatography. Compared to healthy controls, patients had significantly increased lactulose/mannitol ratio and lower postprandial retinyl palmitate and retinyl stearate concentrations. Compared with pre-treatment values, xylose absorption was decreased and lactulose/mannitol and lactulose/xylose ratios were increased during the therapy. A significant decrease of serum alpha-tocopherol was evident throughout the course of therapy. In contrast, only minor alterations of vitamin A absorption were observed. In conclusion, an alteration in intestinal permeability reflected in increased lactulose/mannitol and lactulose/xylose ratios was observed during gefitinib therapy. Potential association between decreased serum alpha-tocopherol concentrations and the toxicity of gefitinib therapy should be further investigated.
- MeSH
- alpha-Tocopherol blood MeSH
- Quinazolines pharmacology therapeutic use MeSH
- Adult MeSH
- Gefitinib MeSH
- Intestinal Absorption drug effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Permeability drug effects MeSH
- Aged MeSH
- Intestines drug effects MeSH
- Case-Control Studies MeSH
- Vitamin A metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- alpha-Tocopherol MeSH
- Quinazolines MeSH
- Gefitinib MeSH
- Vitamin A MeSH
In an earlier study, we have observed an increase of alpha-tocopherol in breast cancer patients treated with third-generation aromatase inhibitors that was related to tamoxifen withdrawal. We report here the results of measurement of alpha-tocopherol in erythrocytes and alpha-tocopherol/cholesterol ratios in patients treated with letrozol. Alpha-tocopherol in lipoprotein fractions and erythrocytes was determined by high-performance liquid chromatography in 124 post-menopausal women with breast cancer treated with letrozol immediately before the start of treatment as well as 2 and 4 mo later. After a transient decrease after 2 mo of letrozol therapy, erythrocyte alpha-tocopherol concentrations returned to pre-treatment levels 4 mo after the start of treatment. Apart from lower cholesterol in patients pre-treated with tamoxifen, no significant differences were observed at baseline between patients previously treated with tamoxifen and patients who had no prior tamoxifen in any of the other parameters investigated, but the transient decrease of erythrocyte alpha-tocopherol was observed only in patients previously treated with tamoxifen. Alpha-tocopherol content of lipoprotein fractions was significantly increased 4 mo after the start of therapy, but this increase was evident mostly in patients not treated earlier with tamoxifen. In conclusion, only minor changes of alpha-tocopherol, including a transient decrease of alpha-tocopherol in erythrocyte membranes, and an increase of alpha-tocopherol in lipoprotein fractions were observed during the first 4 mo of letrozol therapy.
- MeSH
- alpha-Tocopherol blood MeSH
- Cholesterol blood MeSH
- Adult MeSH
- Erythrocytes drug effects metabolism MeSH
- Antineoplastic Agents, Hormonal administration & dosage MeSH
- Cohort Studies MeSH
- Letrozole MeSH
- Middle Aged MeSH
- Humans MeSH
- Breast Neoplasms blood drug therapy MeSH
- Follow-Up Studies MeSH
- Nitriles therapeutic use MeSH
- Antineoplastic Agents therapeutic use MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Tamoxifen administration & dosage MeSH
- Triazoles therapeutic use MeSH
- Chromatography, High Pressure Liquid methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- alpha-Tocopherol MeSH
- Cholesterol MeSH
- Antineoplastic Agents, Hormonal MeSH
- Letrozole MeSH
- Nitriles MeSH
- Antineoplastic Agents MeSH
- Tamoxifen MeSH
- Triazoles MeSH
OBJECTIVE AND BACKGROUND: Asthma is a chronic inflammatory disease in which an oxidant/antioxidant imbalance plays an important role. d-alpha-tocopherol (biologically the most active form of vitamin E) has redox properties and by scavenging the free radicals can act as an antioxidant. The aim of this study was to examine the effects of orally administered alpha-tocopherol in a rat model of allergic asthma. METHODOLOGY: Actively sensitized rats (OA) were treated with alpha-tocopherol (400 mg/kg/day for 10 days) or vehicle; 1 h after the last dose, they were challenged with antigen aerosol. The antigen-induced airway hyperresponsiveness to direct bronchoconstrictor (serotonin), the inflammatory cell infiltrate and histological changes were determined 1 or 24 h after the antigen challenge. RESULTS: Alpha-tocopherol pretreatment was not significantly effective at reducing the studied parameters when compared with controls, even though there was a tendency to a reduction in bronchial responsiveness and in eosinophil and neutrophil infiltration. CONCLUSION: Alpha-tocopherol when administered in the chosen study design in an animal model of asthma had no major effect on airway inflammation. The effect of antioxidants deserves further evaluation.
- MeSH
- Aerosols MeSH
- alpha-Tocopherol administration & dosage therapeutic use MeSH
- Administration, Oral MeSH
- Asthma drug therapy MeSH
- Bronchoalveolar Lavage Fluid chemistry cytology MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Ovalbumin immunology MeSH
- Lung drug effects immunology pathology MeSH
- Rats, Wistar MeSH
- Serotonin pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Aerosols MeSH
- alpha-Tocopherol MeSH
- Ovalbumin MeSH
- Serotonin MeSH
Breast milk is a main source of fat-soluble vitamins for newborns and it is needful to monitor the nutritional status prior to its application. In this work a novel, high-throughput and low-cost method for monitoring of retinol and alpha-tocopherol in breast milk was developed, validated and compared with reference method using monolithic column. For this purpose five various porous shell and monolithic columns were tested on the basis of relationship between HETP and linear mobile phase velocity, analysis time and consumption of solvents. Finally the core-shell analytical column Kinetex C18 (2.6 μm, 100 Å, 100×4.6 mm) was chosen as the best and optimal values of flow rate, injection volume and temperature of analysis were established. The detection of retinol and alpha-tocopherol was carried out at 325 and 295 nm, respectively by diode array detector. The LOD 0.004 μmol/L and 0.078 μmol/L, the LOQ 0.012 μmol/L and 0.182 μmol/L for retinol and alpha-tocopherol, respectively were calculated. The validation data showed good linearity, repeatability of retention time with RSD 0.22% and 0.12%, repeatability of peak area with RSD 6.94% and 1.75%, recovery 114.1-116.3% and 99.0-108.6% for retinol and alpha-tocopherol, respectively. Moreover, the newly developed method substantially decreased the solvent consumption by about 263 mL per 100 samples with the total time of analysis 1.75 min in comparison with analysis time 1.80 of the reference method.
- MeSH
- alpha-Tocopherol analysis MeSH
- Time Factors MeSH
- Humans MeSH
- Limit of Detection MeSH
- Milk, Human chemistry MeSH
- Reproducibility of Results MeSH
- Vitamin A analysis MeSH
- Vitamins analysis MeSH
- Chromatography, High Pressure Liquid economics instrumentation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Validation Study MeSH
- Names of Substances
- alpha-Tocopherol MeSH
- Vitamin A MeSH
- Vitamins MeSH
The reduction of free radicals by bioactive membranes used for hemodialysis treatment is an important topic due to the constant rise of oxidative stress-associated cardiovascular mortality by hemodialysis patients. Therefore, it is urgent to find an effective solution that helps to solve this problem. Polysulfone membranes enriched with α-lipoic acid, α-tocopherol, and with both components are fabricated by spin coating. The antioxidant properties of these membranes are evaluated in vitro by determining the lipid-peroxidation level and the total antioxidant status of the blood plasma. The biocompatibility is assessed by quantifying the protein adsorption, platelet adhesion, complement activation, and hemolytic effect. All types of membranes show in vitro antioxidant activity and a trend to reduce oxidative stress in vivo; the best results show membranes prepared with a combination of both compounds and prove to be nonhemolytic and hemocompatible. Moreover, the membrane specific separation ability for the main waste products is not affected by antioxidants incorporation.
- Keywords
- alpha-lipoic acid, alpha-tocopherol, hemodialysis, oxidative stress, polysulfone membranes,
- MeSH
- Adsorption MeSH
- Platelet Activation drug effects MeSH
- alpha-Tocopherol pharmacology MeSH
- Antioxidants pharmacology MeSH
- Renal Dialysis * MeSH
- Adult MeSH
- Erythrocytes drug effects metabolism MeSH
- Blood Coagulation drug effects MeSH
- Complement System Proteins metabolism MeSH
- Thioctic Acid pharmacology MeSH
- Humans MeSH
- Membranes, Artificial * MeSH
- Urea chemistry MeSH
- Oxidative Stress drug effects MeSH
- Polymers pharmacology MeSH
- Porosity MeSH
- Sulfones pharmacology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- alpha-Tocopherol MeSH
- Antioxidants MeSH
- Complement System Proteins MeSH
- Thioctic Acid MeSH
- Membranes, Artificial * MeSH
- Urea MeSH
- Polymers MeSH
- polysulfone P 1700 MeSH Browser
- Sulfones MeSH
In this work, a simple isocratic reversed-phase HPLC method for determination of alpha-tocopherol in human erythrocytes has been developed and validated. After separation of plasma the erythrocytes were washed three times with 0.9% sodium chloride containing 0.01% butylated hydroxytoluene (BHT) as antioxidant and then were diluted 1:1 (v/v) with the same solution. In the liquid-liquid extraction (LLE) procedure, 2500 microL of n-hexane was added to 500 microL of erythrocytes. After 2 min this mixture was deproteinized by addition of cool ethanol (500 microL, 5 min) denatured with 5% methanol containing alpha-tocopherol acetate (20 micromol L(-1)), as internal standard, and then extracted for 5 min by vortex mixing. After centrifugation (10 min, 1600xg) an aliquot (2000 microL) of the clean extract was separated and evaporated under nitrogen. The residue was dissolved in 400 microL methanol and analysed by reversed-phase HPLC on a 4.6 mmx150 mm, 5 microm Pecosphere C18 column; the mobile phase was 100% methanol, flow rate 1.2 mL min(-1). The volume injected was 100 microL and detection was by diode-array detector at a wavelength of 295 nm. The extraction recovery of alpha-tocopherol from human erythrocytes was 100.0+/-2.0%. The detection limit was 0.1 micromol L(-1) and a linear calibration plot was obtained in the concentration range 0.5-20.0 micromol L(-1). Within determination precision was 5.2% RSD (n=10), between determination precision was 6.1% RSD (n=10). The method was applied successfully in a clinical study of patients with acute pancreatitis and for determination of the reference values in the healthy Czech population.
- MeSH
- Acute Disease MeSH
- alpha-Tocopherol analysis MeSH
- Adult MeSH
- Erythrocytes chemistry MeSH
- Calibration MeSH
- Middle Aged MeSH
- Humans MeSH
- Pancreatitis blood MeSH
- Reference Standards MeSH
- Aged MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Validation Study MeSH
- Names of Substances
- alpha-Tocopherol MeSH
Administration of imatinib is the therapy of choice in patients with advanced (inoperable) or metastatic gastrointestinal stromal tumors (GIST). Gastrointestinal toxicity is one of the most common side effects of anticancer therapy, including imatinib. Measurement of intestinal permeability represents a method of noninvasive laboratory assessment of gastrointestinal toxicity. We have measured intestinal permeability (by determining absorption of lactulose, mannitol and xylose), vitamin A absorption and serum alpha-tocopherol in 16 patients with advanced/metastatic GIST treated with imatinib. Lactulose/mannitol and lactulose/xylose ratios as well as parameters of vitamin A absorption did not change significantly during the treatment, but a significant decrease of alpha-tocopherol was observed. We conclude that, in contrast to most other anticancer agents studied so far, imatinib does not have an effect on intestinal permeability. No effect on vitamin A absorption was observed, but serum alpha-tocopherol decreased significantly during the treatment.
- MeSH
- alpha-Tocopherol blood MeSH
- Benzamides MeSH
- Adult MeSH
- Gastrointestinal Stromal Tumors blood drug therapy metabolism MeSH
- Imatinib Mesylate MeSH
- Intestinal Absorption drug effects MeSH
- Dietary Sucrose pharmacokinetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Permeability MeSH
- Piperazines pharmacology therapeutic use MeSH
- Antineoplastic Agents pharmacology therapeutic use MeSH
- Pyrimidines pharmacology therapeutic use MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Intestinal Mucosa drug effects metabolism MeSH
- Vitamin A pharmacokinetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- alpha-Tocopherol MeSH
- Benzamides MeSH
- Imatinib Mesylate MeSH
- Dietary Sucrose MeSH
- Piperazines MeSH
- Antineoplastic Agents MeSH
- Pyrimidines MeSH
- Vitamin A MeSH
High serum or urinary neopterin concentrations are associated with poor prognosis in patients with tumors of different primary locations, but reports on neopterin in patients with head and neck carcinoma are relatively less numerous. It has been established that decreased circulating concentrations of retinol and alpha-tocopherol are common in this population. We have evaluated the prognostic significance of urinary neopterin, serum retinol, and alpha-tocopherol in 44 patients with head and neck carcinoma. Urinary neopterin, serum retinol, and alpha-tocopherol were determined with high-performance liquid chromatography. High urinary neopterin and low serum retinol were predictive of poor prognosis, while the prognostic significance of low alpha-tocopherol was of borderline significance. Serum retinol significantly decreased during external beam radiation, but a less marked decrease of alpha-tocopherol during therapy did not reach statistical significance. An increase of urinary neopterin was evident late during the course of treatment. In conclusion, high urinary neopterin and low serum retinol are predictive of poor prognosis in patients with head and neck carcinoma.
- MeSH
- alpha-Tocopherol blood MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Head and Neck Neoplasms blood radiotherapy urine MeSH
- Neopterin urine MeSH
- Prognosis MeSH
- Aged MeSH
- Vitamin A blood MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- alpha-Tocopherol MeSH
- Neopterin MeSH
- Vitamin A MeSH
Although gastrointestinal toxicity is one of the most common side effects of anticancer therapy, the diagnosis and assessment of this toxicity still depend mostly on anamnestic data. Measurement of intestinal permeability is one of potential methods of non-invasive laboratory evaluation of gastrointestinal toxicity. The aim of the present study was to investigate intestinal permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin in patients with rectal carcinoma treated with chemoradiation. We have studied intestinal permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin in 17 patients with rectal carcinoma treated with chemoradiation. Urinary lactulose, mannitol, and xylose were measured by capillary gas chromatography, and serum alpha-tocopherol, retinol, retinyl esters, and urinary neopterin were determined by high-performance liquid chromatography. Lactulose/mannitol ratio was increased 5 and 6 weeks after the start of the treatment. Serum alpha-tocopherol was decreased significantly throughout the course of treatment, but no significant changes were observed in postprandial serum concentrations of retinyl esters or in the concentrations of urinary neopterin. A correlation was observed between baseline parameters of intestinal permeability and urinary neopterin. The measurement of intestinal permeability using the lactulose/mannitol test may represent a sensitive tool in the detection of changes associated with chemoradiation in patients with rectal carcinoma. The therapy is also associated with a decrease of alpha-tocopherol.
- MeSH
- Adenocarcinoma drug therapy immunology metabolism radiotherapy MeSH
- alpha-Tocopherol blood MeSH
- Antioxidants metabolism MeSH
- Chromatography, Gas MeSH
- Dietary Carbohydrates pharmacokinetics MeSH
- Diterpenes MeSH
- Fluorouracil adverse effects therapeutic use MeSH
- Intestinal Absorption * drug effects radiation effects MeSH
- Combined Modality Therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Rectal Neoplasms drug therapy immunology metabolism radiotherapy MeSH
- Neopterin urine MeSH
- Antimetabolites, Antineoplastic adverse effects therapeutic use MeSH
- Retinyl Esters MeSH
- Carbohydrates urine MeSH
- Aged MeSH
- Vitamin A administration & dosage analogs & derivatives blood pharmacokinetics MeSH
- Radiotherapy, High-Energy adverse effects MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- alpha-Tocopherol MeSH
- Antioxidants MeSH
- Dietary Carbohydrates MeSH
- Diterpenes MeSH
- Fluorouracil MeSH
- Neopterin MeSH
- Antimetabolites, Antineoplastic MeSH
- retinol palmitate MeSH Browser
- Retinyl Esters MeSH
- Carbohydrates MeSH
- Vitamin A MeSH
