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PubMed2004

Ascorbic acid in nasal and tracheobronchial airway lining fluids.

Ascorbic acid (AA) is thought to be an important antioxidant in the respiratory tract, whose regulation is yet to be fully characterized. We investigated whether AA in respiratory tract lining fluids (RTLFs) can be augmented by oral supplementation with AA. Plasma, nasal lavage fluids (NLFs), induced sputum (IS), and saliva were analyzed for AA immediately before and 2 h after ingestion of 2 g of AA in 13 healthy subjects. Concentrations of AA (median and range) were 52.5 (16.0-88.5), 2.4 (0.18-4.66), 2.4 (0.18-6.00), and 0.55 (0.18-18.90) micromol/l, respectively. Two hours after ingestion of AA, plasma AA increased 2-fold (p = .004), NLF AA increased 3-fold (p = .039), but IS and saliva AA did not increase. As AA concentrations in saliva and tracheobronchial secretions were low compared with other common extracellular components (such as urate), we evaluated the fate of AA in these fluids. Addition of AA to freshly obtained saliva or IS resulted in rapid depletion, which could be largely prevented or reversed by sodium azide or dithiothreitol. These findings suggest that oxidant-producing systems in saliva and airway secretions, such as heme peroxidases and other oxidizing substances, rapidly consume AA. Whereas oral supplementation resulted in detectable increases of AA in NLFs, its levels in tracheobronchial lining fluid, as measured by IS, were unaffected and remained relatively low, suggesting that AA may play a less significant antioxidant role in this compartment as compared with most other extracellular compartments.

Administration, Oral↗
PubMed2005

Antioxidative and anti-inflammatory effects of repaglinide in plasma of diabetic animals.

Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense, is considered to be an important pathogenic factor in diabetes mellitus and its complications. In diabetic state, ROS might also be implicated in promoting a state of systemic inflammation. Recently, it was demonstrated that antioxidant therapy could be used to stop the initiation and propagation of this inflammatory response. Repaglinide is a new oral antidiabetic agent with a possible antioxidant activity. Therefore, in the present study, a possible therapeutic value of repaglinide in ameliorating the oxidative and inflammatory processes was tested in diabetic animals. In the study, the levels of total antioxidant status (TAS), ascorbic acid (AA), protein carbonyl groups (PCG) and interleukin-6 (IL-6) were determined in plasma of diabetic rabbits after 4 and 8 weeks of repaglinide treatment (1mg daily). Ex vivo analysis revealed that there were significant differences in these markers between hyperglycemic and control animals (P<0.05). Some of these parameters were ameliorated by repaglinide treatment. In diabetic rabbits treated with repaglinide, protein oxidation was diminished by 17.8% after 8 weeks of experiment. The level of AA in plasma of diabetic treated animals was higher than in non-treated diabetic groups (by 9.4 and 22.6% after 4 and 8 weeks, respectively). In diabetic treated animals, the TAS level was also significantly increased (by 23.6 and 16.7%). However, in diabetic rabbits, repaglinide did not affect the concentration of IL-6.

Animals↗
PubMed2005

Anti-angiogenic effects of a nutrient mixture on human umbilical vein endothelial cells.

Matrix metalloproteinases (MMPs) have been recognized as key players in the degradation of the extracellular matrix (ECM) by migration and proliferation of endothelial cells and their subsequent invasion of the underlying stroma. The prevention of ECM degradation through the inhibition of MMP activity has been shown to be a promising therapeutic approach to block the invasion that occurs during angiogenesis. In previous studies, we demonstrated the anti-tumor effect of a nutrient mixture (NM) containing ascorbic acid, lysine, proline, green tea extract, arginine, N-acetyl cysteine, selenium, copper and manganese on various tumor cell lines in vivo and in vitro. The aim of the present study was to determine whether this mixture has anti-angiogenic effects on human umbilical vein endothelial cells (HUVECs). At near confluence, the HUVEC cell cultures were tested with NM at 0, 10, 50, 100, 500, and 1000 microg/ml in triplicate at each dose for proliferation, migration, MMP expression, and invasion. Cell proliferation was evaluated by MTT assay, invasion potential by Matrigel invasion, MMP expression by gelatinase zymography, and cell migration by a 2 mm-wide scratch in plates. For tube formation, HUVECs were cultured in previously polymerized Matrigel. NM inhibited HUVEC migration, MMP expression and invasion through Matrigel in a dose-dependent manner. Zymography showed a dose-dependent inhibition of MMP-2 expression with virtual total inhibition at a 500 microg/ml concentration. Invasion through Matrigel was totally inhibited at 500 microg/ml NM. NM reduced cell migration by scratch test in a dose-dependent fashion with total inhibition at a 500 microg/ml concentration. NM also inhibited the tube formation of HUVECs, but did not significantly inhibit cell proliferation. These results together with our earlier findings suggest that NM is a relatively non-toxic formulation with anti-angiogenic effects, such as inhibiting vascular tube formation and endothelial cell invasion and migration.

Acetylcysteine↗
PubMed1996

[Work conditions and health status of workers in present-day production of disperse azo dyes].

The work conditions appeared to be unfavorable in modern production of dispersed nitro dyes, having up-to-date technologic equipment and automated control systems. The main occupational hazards are semiproducts (nitroaniline derivatives containing chlorine, bromine and cyanides) used as diazo components in dyes synthesis, dispersers based on sodium lignosulfonate, outlet forms of dispersed nitro dyes. Medical examination of the workers exposed to combination of chemicals amounting several times over the MACs proved frequent diseases of upper respiratory tract and cardiovascular system, functional disorders of liver and CNS, propensity for allergic conditions. Specific effects of dispersed nitro dyes and semiproducts of their synthesis on the red blood were methemoglobin formation, suppressed antioxidant activity of RBC (lower serum level of reduced glutathione and ascorbic acid) and stimulated erythropoiesis in bone marrow (increased serum Hb and RBC count, reticulocytosis). The studies helped to elaborate well-justified complex of sanitary, hygienic, therapeutic and prophylactic measures to better the work conditions and prevent the occupational diseases among the workers.

Azo Compounds↗
PubMed1990

Effect of a new synthetic free radical scavenger, 2-octadecyl ascorbic acid, on the mortality in mouse endotoxemia.

Oxygen-derived free radicals have been implicated as mediators of cellular injury in several model systems. In order to clarify the role of oxygen radicals in endotoxemia, we measured the serial lipid peroxide changes resulting from systemic radical reactions using a newly developed colormetric method. To determine the effect of a free radical scavenger on mortality in endotoxemia, a new synthetic scavenger, 2-Octadecylascorbic acid (CV-3611), which overcome the detrimental properties (circulation half-life and cell penetration) of native SOD, was used in the model of mouse endotoxemia induced by the i.p. administration of E-coli endotoxin (10 mg/kg). Serial LPO (Lipid Peroxide) changes revealed significant elevations from the basal level of 4.52 +/- 0.79 nmol/ml to 10.5 +/- 2.04 nmol/ml at 2h (P less than 0.05), 12.0 +/- 2.44 nmol/ml at 8h (P less than 0.05), 32.8 +/- 12.5 nmol/ml at 12h (P less than 0.05) and 13.6 +/- 2.40 nmol/ml at 24h (P less than 0.05) following i.p. administration of E-coli. The circulation half life of CV-3611 was checked by a reversed-phase HPLC after 10 mg/kg s.c. administration. The level of CV-3611 reached peak levels of 0.54 +/- 0.10 micrograms/ml at 1h and 0.52 +/- 0.20 micrograms/ml at 2h then gradually decreased to the level of 0.04 +/- 0.004 micrograms/ml at 6h and to a non-detectable level at 24h after s.c. administration. Increased survival was seen at 2 days (P less than 0.001) after E-coli endotoxin administration in the CV-3611 treated group compared to the control group. These results suggest that oxygen derived free radicals contribute to mortality in mouse endotoxemia and that antioxidants such as CV-3611 may provide a new therapeutic avenue by improving survival of patients with gram-negative bacterial sepsis.

Animals↗
PubMedDate not supplied

Growth inhibitors in the treatment of malignant neoplasms.

Growth inhibitors are an integral part of the regulatory mechanisms involved in the growth and differentiation of cells and tissues. Aberration in the response to growth inhibitors leads to the escape of the cell from the cell cycle control mechanisms and may lead to the development of malignancies. The inactivation of tumor suppressor genes, activation of oncogenes leads to the acquisition of an invasive and increasingly malignant immunophenotype and secretory profile by transformed cells. The commencement of the complex process of carcinogenesis, and subsequent, rapid tumor growth and progression of mammalian neoplasms depends upon the continuous de novo formation of capillaries (angiogenesis). The generation of a malignant, invasive cellular immunophenotype (CIP) and distant metastases, as aspects of tumor progression, are also NRA-dependent processes. Specific molecules with cytostatic/cytotoxic growth inhibitory effects represent a very diverse group of factors. Growth inhibitors may regulate the cell cycle at various levels, and growth inhibitors comprise a heterogeneous group of agents including cytokines, growth factors, steroid hormones, etc. The phenomenon of multidrug resistance to a wide spectrum of cytostatic/cytotoxic agents has posed a major difficulty in the effective chemotherapeutical treatment of cancer patients. The development of novel therapeutic regimens should be based on the observations of the growth inhibitory profile of the particular malignancy, in addition to its immunophenotype and genotype, and the devisement of 'individualized' combinations of factors, including gene and immuno-therapeutical options, targeting different aspects of the malignant disease.

Ascorbic Acid↗
PubMed2001

Differences in antioxidant status in skeletal muscle tissue in experimental diabetes.

BACKGROUND: It has been suggested that oxidative stress may play an important role in pathogenesis of diabetic complications. The present study was designed to evaluate the oxidative stress-related parameters in alloxan (A)-induced long-term diabetes in rabbits. METHODS: After 3, 6 and 12 weeks of diabetes, activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and concentrations of ascorbic acid (AA) and free sulfhydryl compounds (SH) were measured in skeletal muscle of diabetic rabbits and the normal control subjects. The products of lipid peroxidation (MDA) were also estimated. RESULTS: In our tests, the muscle SOD activity, SH and AA concentrations were significantly reduced. CAT activity increased significantly at all time intervals. GSH-Px activity decreased after 3 weeks and then remained at the control level. GSSG-R activity decreased progressively at 3rd and 6th week and then significantly increased. MDA level increased initially, dropped below baseline after 6 weeks and then remained at the level of the control group. CONCLUSIONS: The changes observed in the present experiment suggest a significant imbalance in antioxidative system in the skeletal muscle of rabbits with alloxan-induced diabetes. Such study may lead to therapeutic approaches for limiting the damage from oxidation reactions and preventing the diabetic complications.

Animals↗
PubMed1979

Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial.

One hundred and fifty patients with advanced cancer participated in a controlled double-blind study to evaluate the effects of high-dose vitamin C on symptoms and survival. Patients were divided randomly into a group that received vitamin C (10 g per day) and one that received a comparably flavored lactose placebo. Sixty evaluable patients received vitamin C and 63 received a placebo. Both groups were similar in age, sex, site of primary tumor, performance score, tumor grade and previous chemotherapy. The two groups showed no appreciable difference in changes in symptoms, performance status, appetite or weight. The median survival for all patients was about seven weeks, and the survival curves essentially overlapped. In this selected group of patients, we were unable to show a therapeutic benefit of high-dose vitamin C treatment.

Aged↗
PubMed1985

In vitro drug interference with home blood-glucose-measurement systems.

The in vitro effects of ascorbic acid, acetaminophen, salicylic acid, and gentisic acid on home blood-glucose-measurement systems were studied. Whole blood in the normoglycemic range was spiked with quantities of each study drug at low, moderate, and high therapeutic concentrations. The glucose concentration of the blood was measured using Chemstrip bG, Dextrostix, and Visidex II home blood-glucose-monitoring systems. Serum samples were also measured by two automated systems, a glucose-oxidase method and a hexokinase method. Mean values were compared within the same glucose-measurement system to determine the extent of drug interference, and to values obtained by other systems to determine the reliability among systems. Changes between the control and treatment glucose mean concentrations of 20% or more were considered clinically important. Drug interference was observed with all three home blood-glucose-measurement systems and was drug-concentration dependent. Both automated systems were associated with drug interference at the highest concentration of salicylic acid, and the hexokinase method was influenced at the highest concentration of gentisic acid. No clinically important differences were observed between the automated systems; however, differences were observed between the automated and home blood-glucose-monitoring systems. Salicylic acid, acetaminophen, and ascorbic acid interfere with home blood-glucose-measurement systems. Switching between home blood-glucose-measurement systems could result in a poor assessment of blood-glucose values. In general, the values determined by home and automated systems should not be compared clinically.

Acetaminophen↗