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PubMed2004

Oxidative stress and antioxidant supplementation in the management of diabetic cardiovascular disease.

The diabetic state confers an increased propensity to accelerated atherogenesis. In addition to the established risk factors, there is evidence for increased oxidative stress in diabetes. Increased oxidative stress is manifested by increased lipid peroxidation, increased F2-isoprostanes, increased nitrotyrosine, and increased DNA damage. Also, in diabetics, there is increased superoxide release. With regard to diabetes, antioxidants such as alpha-tocopherol, alpha-lipoate, and ascorbic acid supplementation have been shown to be beneficial. Most importantly, alpha-tocopherol therapy, especially at high doses, clearly shows a benefit with regard to low-density lipoprotein oxidation, isoprostanes, and monocyte superoxide release. Thus, it appears that, in diabetes, antioxidant therapy could alleviate the increased attendant oxidative stress and emerge as an additional therapeutic modality.

Antioxidants↗

PubMed1982

Some new data to the toxicological effects of paraquat and the therapy.

1. Substances previously tested therapeutically were studied to obtain evidence on the pathomechanism in mice of paraquat, the active ingredient of Gramoxon, connected with the radicals formed from molecular oxygen, and also to extend the therapeutic possibilities. 2. The effects of these substances were assessed on the basis of the 72-hr survival rate and the percentage ratio of the wet lung weight to the overall body weight. 3. Other toxicological parameters too were followed. 4. Our present investigations indicate that, in agreement with our earlier results, besides reduced glutathione and ascorbic acid, vitamin E and C-ase are of the greatest importance from the aspect of the protection against paraquat toxicity. 5. In addition to those listed, other materials too, e.g. antifibrotic substances, naturally possess considerable detoxicating properties too.

Animals↗

PubMed1994

Antioxidant status in asthma.

Reduced levels of glutathione peroxidase (GSH-Px) have been observed in adults with asthma. This study examines the antioxidant status in children with asthma compared with a control group in a cross-sectional analysis. Red blood cell GSH-Px, superoxide dismutase (SOD), and plasma concentrations of retinol, vitamin C, alpha tocopherol, and cholesterol were measured in 37 subjects (26 males) with stable controlled asthma. Thirty-five subjects (20 males) without eczema, hayfever, or recurrent respiratory symptoms were used as a control group. Children with asthma had significantly reduced red blood cell GSH-Px activity compared with controls [median (inter-quartile range) for asthma group, 10.25 (9.25-11.91); for control group, 11.75 (10.34-12.26) IU/g Hb; P = 0.006]. There were no significant differences in activity of SOD or vitamin C, retinol, or alpha tocopherol/cholesterol ratio. The reduction in GSH-Px activity may have therapeutic and etiological implications for asthma. The effects of disease activity and treatment on antioxidant status needs for further study.

Adolescent↗

PubMed1977

Chelation in metal intoxication. IV. Removal of chromium from organs of experimentally poisoned animals.

In an attempt to find more reliable therapeutic or preventive agents for industrial chromium poisoning, some structurally different metal binding agents were screened for their ability to mobilize chromium from liver, kidney, brain, and testes (in vivo) and their subcellular fractions (in vitro), together with the blood corpuscles of experimentally intoxicated animals. Ethylenedinitrilotetraacetic acid (EDTA) and diethylenetriamine pentaacetic acid (DTPA) were quite successful in vivo, while ascorbic acid and 3,4-dihydroxy-L-phenyl alanine (L-DOPA) were more effective in vitro. No relationship could be observed between the structure or the molecular weight of the various chelating agents examined and their ability to remove chromium from either the tissue or their subcellular fractions.

Animals↗

PubMed1990

Factors influencing the formation of methemoglobin in desferrioxamine loaded erythrocytes.

Desferrioxamine (DFO) in therapeutically useful amounts was incorporated into red blood cells (RBC) by means of a dialysis method. Entrapped DFO interacted with hemoglobin which was indicated by the formation of methemoglobin. This process was influenced to a great extent by the duration and temperature of the incubation steps. In contrast to added methylene blue the co-entrapment of ascorbic acid proved to be a very effective measure for protecting hemoglobin from oxidation and maintaining intracellular 2,3-diphosphoglycerate (2,3-DPG). Hypernormal values of 2,3-DPG could be obtained by the incubation in solutions containing phosphate, inosine, and pyruvate. Loaded RBC prepared in such a way should be characterized by a nearly normal oxygen-transport function and survival in vivo.

2,3-Diphosphoglycerate↗

PubMed1976

Interactions of nutrition and infection.

Interactions between malnutrition and infection contribute directly to the health of individuals and communities. The relevance of this concept to the practice of clinical medicine, dentistry, and public health is supported by an imposing collection of evidence from the clinic, laboratory, and field. Malnutrition can interfere with any body mechanism that acts as a barrier to the multiplication or progress of infectious agents. This includes formation of specific antibodies, number and activity of phagocytes, integrity of skin, mucous membranes, and other tissues. Some of the less definite, nonspecific protective substances in body fluids are also affected by malnutrition. Infectious disease adversely influences the nutritional state in several indirect ways. Loss of appetite and intolerance for food result in metabolic changes. Cultural factors lead to substitution of less nutritious diets as a presumed therapeutic measure and to administration of purgatives, antibiotics, and other medicines that reduce digestion or absorption of specific nutrients. All of these may help to precipitate kwashiorkor in children subsisting on protein-deficient diets. Classical nutritional deficiencies precipitated by infection in individuals with borderline nutrient depletion include: keratomalacia due t avitaminosis-A; scurvey from lack of ascorbic acid; beriberi as a consequence of inadequate thiamin; pellagra resulting from insufficient niacin; macrocytic anemia due to folic acid or vitamin B12 deficiency; and microcytic anemia resulting from a shortage of iron. In well nourished individuals, body reserves and normal dietary intake assure that malnutrition will not result unless infection is prolonged.

Antibody Formation↗

PubMed2001

In vitro phagocytosis of carrier mouse red blood cells is increased by Band 3 cross-linking or diamide treatment.

Chemical alteration of red blood cells (RBCs) can induce increased phagocytosis of modified cells by macrophages. In this study we have used different chemical treatments for the modification of the mouse red-blood-cell membrane surface, namely oxidant compounds, such as ascorbate/Fe(+2) and diamide [azodicarboxylic acid bis(dimethylamide)], or Band 3-cross-linking reagents. We monitored the phagocytosis of oxidized or Band 3-cross-linked mouse red blood cells by peritoneal macrophages. The extent of phagocytosis of RBCs is not affected by oxidation with ascorbate/Fe(3+), but it is increased (up to 10%) by oxidation with 2 mM diamide. Furthermore, phagocytosis is greatly increased (up to 40%) as a result of cross-linking with either of two Band 3 bifunctional reagents [bis(sulphosuccinimidyl) suberate (BS(3)) and 3,3'-dithiobis(sulphosuccinimidyl propionate) (DTSSP)]. To evaluate targeting towards macrophages of such modified RBCs for therapeutical purposes, we have determined the phagocytosis of Band 3 carrier RBCs loaded with carbonic anhydrase. In this case phagocytosis is high enough (25%) to deliver the enzyme into macrophages. We have also assayed the influence of serum components and IgG on the efficiency of phagocytosis and discuss the possible phagocytosis mechanisms. In the case of BS(3)-cross-linked carrier RBCs, phagocytosis is markedly enhanced (from 12% up to 25%) by serum components. This opens a way for therapeutic application of these carrier RBCs, with special relevance in short-term delivery to cells of the mononuclear phagocytic system.

Animals↗

PubMed2006

Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid combination therapy in patients with relapsed or refractory multiple myeloma: a prospective, multicentre, phase II, single-arm study.

We assessed the safety and efficacy of melphalan, arsenic trioxide (ATO) and ascorbic acid (AA) (MAC) combination therapy for patients with multiple myeloma (MM) who failed more than two different prior regimens. Patients received melphalan (0.1 mg/kg p.o.), ATO (0.25 mg/kg i.v.) and AA (1 g i.v) on days 1-4 of week 1, ATO and AA twice weekly during weeks 2-5 and no treatment during week 6 of cycle 1; during cycles 2-6, the schedule remained the same except ATO and AA were given twice weekly in week 1. Objective responses occurred in 31 of 65 (48%) patients, including two complete, 15 partial and 14 minor responses. Median progression-free survival and overall survival were 7 and 19 months respectively. Twenty-two patients had elevated serum creatinine levels (SCr) at baseline, and 18 of 22 (82%) showed decreased SCr levels during treatment. Specific grade 3/4 haematological (3%) or cardiac adverse events occurred infrequently. Frequent grade 3/4 non-haematological adverse events included fever/chills (15%), pain (8%) and fatigue (6%). This steroid-free regimen was effective and well tolerated in this heavily pretreated group. These results indicate that the MAC regimen is a new therapeutic option for patients with relapsed or refractory MM.

Adult↗

PubMed1998

The effects of glucosamine and chondroitin sulfate on osteoarthritis of the TMJ: a preliminary report of 50 patients.

The signs and symptoms of osteoarthritis are common complaints seen in patients suffering with chronic temporomandibular disorders (TMD), specifically, internal derangements with a diagnosis of osteoarthritis. With or without the complaints of pain and swelling, joint noises are bothersome and annoying to both the patient and at times, to those seated close to the patient during mealtime. In fact, many patients are driven to seek care by family members because of his or her TMJ noises. For years in veterinarian medicine, glucosamine and chondroitin sulfates have been used to treat symptoms of osteoarthritis. Recently, the use of these two supplements has been recommended for human beings as well. Reports of decreased joint noises, pain and swelling after the administration of therapeutic doses of these supplements have sparked an interest in their possible use in the treatment of osteoarthritis.

Adolescent↗

PubMed2004

The role of BMP-6, IL-6, and BMP-4 in mesenchymal stem cell-dependent bone development: effects on osteoblastic differentiation induced by parathyroid hormone and vitamin D(3).

Human bone marrow-derived mesenchymal stem cells (MSCs) represent an ideal source for cell therapy for inherited and degenerative diseases, bone and cartilage repair, and as target for gene therapy. The role of the combination of human parathyroid hormone (PTH) and vitamin D(3) in bone formation and mineralization has been established in several osteoblast cell culture studies. The aim of the present study was to evaluate the role of this hormonal combination alone and in the presence of bone morphogenetic protein-4 (BMP-4) or-6 (BMP-6) in inducing osteogenic differentiation of human MSC. Human MSC derived from adult normal bone marrow that are positive for CD29, CD44, CD105, and CD166 and negative for CD14, CD34, and CD45, were treated with the PTH and 1,25-dihydroxyvitamin D(3) in the presence and absence of recombinant human BMP-4 or BMP6. PTH and vitamin D(3) induced high levels of expression of two key markers of bone formation: osteocalcin and alkaline phosphatase by MSCs. BMP-6 but not BMP-4 increased osteocalcin expression induced by PTH and vitamin D(3). Both BMPs enhanced calcium formation in MSC cultures and this response was potentiated by PTH and vitamin D(3). The present results revealed a novel potent effect of PTH and vitamin D(3) plus BMPs in inducing bone development by human MSCs. These results may facilitate therapeutic utility of MSCs for bone disease and help clarify mechanisms involved in stem cell-mediated bone development.

Adult↗

PubMed2001

Acute effects of vitamin C on platelet responsiveness to nitric oxide donors and endothelial function in patients with chronic heart failure.

Chronic heart failure (CHF) is characterized by a prothrombotic state, which may relate to increased platelet aggregability, endothelial dysfunction, and increased oxidative stress. We investigated the effect of vitamin C in CHF on ex vivo platelet aggregation and platelet responsiveness to the anti-aggregatory effects of the nitric oxide (NO) donors glyceryl trinitrate (GTN) and sodium nitroprusside (SNP). We also examined parameters of oxidative stress and endothelial function in patients. In this double-blind, randomized, crossover study vitamin C (2 g) or placebo was given intravenously to 10 patients with CHF. We measured adenosine 5-diphosphate (ADP)-induced platelet aggregation, flow-mediated dilatation (FMD) in the brachial artery using ultrasonic wall-tracking, and plasma levels of lipid-derived free radicals using electron paramagnetic resonance spectroscopy. Vitamin C did not affect ex vivo platelet aggregability but enhanced the inhibition of platelet aggregation by SNP (62.7+/-10.2 to 82.7+/-4.8%, p = 0.03) and tended to increase responses to GTN (40.5+/-9.0 to 53.4+/-7.3, p = 0.06). The effect of vitamin C on platelet responsiveness to the antiaggregatory effects of SNP was inversely related to basal response to SNP (r = -0.9, p < 0.01); a similar trend was observed with GTN (r = -0.6, p = 0.1). Vitamin C also increased FMD (1.9+/-0.6 to 5.8+/-1.5%, p = 0.02) and reduced plasma lipid-derived free radicals by 49+/-19% (p < 0.05). In patients with CHF acute intravenous administration of vitamin C enhances platelet responsiveness to the anti-aggregatory effects of NO donors and improves endothelial function, suggesting a potential role for vitamin C as a therapeutic agent in CHF.

Adult↗

PubMed2006

Free radicals: emerging challenge in environmental health research in childhood and neonatal disorders.

Infants and children may undergo severe oxidative stress due to disease state, pre-existing nutritional status, frequent use of oxygen, and lower levels of antioxidant defenses. Antioxidant defenses, made up of intracellular and extra-cellular components, work synergistically to prevent oxidative damage. Total antioxidant activity (TAA) was analyzed by method of ferric reducing antioxidant power assay (FRAP). Patients admitted in Pediatric Dept, RNT Medical College, Udaipur, India were selected for these studies. TAA level in neonates with hypoxic-ischemic-encephalopathy (HIE) stage III and in poor outcome cases was significantly low. Erythrocyte SOD activity level was low in pre-term neonates. TAA level in severely malnourished children at the time of hospital admission was low. This low antioxidant level in severely malnourished children could be multi-factorial viz. low zinc, selenium, vitamin A & C deficiency, recurrent infections, elevated free iron and chronic starvation stage. Delayed recovery of oxidant injury may lead to delayed incomplete recovery at cellular level. In a study of 29 tuberculosis patients TAA level was found to be low in tubercular patients compared with control. TAA level decreased more in CNS tuberculosis compared with other system tuberculosis. In a study of nutritional tremor syndrome TAA, ascorbic acid and alpha-tocopherol levels were low during pre-tremor phase compared with tremor phase (ATS). Pre-term neonates have incompletely developed antioxidant defenses and are deficient in vitamin E, which is normally derived from maternal circulation at the end of 3rd trimester. Therefore, decreased TAA level in HIE with poor outcome indicates addition of antioxidants in therapeutic strategy. Since rise in TAA in antioxidant supplemented group of severely malnutrition children was higher with good outcome compared with nonsupplemented group it would be prudent to supplement antioxidant during nutritional management. These studies have shown that health benefits can be obtained by children with a reduced risk of disease from supplements of antioxidant nutrients. The amounts of optimal supplements in these disorders, whether pharmacologic or large, are to be determined. Further work is needed to show whether modest increases in nutrient intakes in children with these disorders will delay or prevent the complications and improve the outcome. Therefore, available evidence regarding health benefits to be achieved by supplementing antioxidant nutrients is encouraging. Free radical injury and antioxidant deficiency is more common than what we think. Severely malnourished children and children suffering from chronic infections and diseases are at several fold increased risk of antioxidant deficiency and likely to suffer from free radical injury. Appropriate interventions are required in reducing the risk associated with these observations.

Child↗

PubMed2001

The role of antioxidant vitamins (C and E), selenium and Nigella sativa in the prevention of liver fibrosis and cirrhosis in rabbits: new hopes.

This experiment was carried out to investigate the role of antioxidants such as vitamin C and E, selenium and Nigella sativa (NS) on the prevention of carbon tetrachloride (CCl4)-induced liver fibrosis in rabbits. It was found that superoxide dismutase (SOD) values in all of the treated groups were significantly lower than those of the control at 12th week of experiment (p < 0.05), while at 6th week and 12th week of experiment glutathione peroxidase (GSH-Px) values in the vitamin C treated group were significantly different from the control (p < 0.05). Histopathologically, hepatocellular necrosis, degeneration and advanced fibrosis were found in the control group. Lesions were minor and only confined to midzonal regions without centrilobular necrosis and fibrosis in the NS treated animals (group B). The lesions observed in the vitamin C treated animals (group C) were similar to that of the control group. Parenchymal changes with fibrosis were less in selenium and vitamin E treated animals (group D) than in those of the control group, but more obvious than in NS group. Histopathological findings demonstrate that NS might, at least partly, be successful in the prevention of liver fibrosis in rabbits. Vitamin E plus selenium had little therapeutic effect and vitamin C seemed to be ineffective, as far as the results of this study are concerned.

Animals↗

PubMed1982

Skeletal changes associated with copper deficiency.

Copper deficiency has been described in premature infants on hyperalimentation. The bony abnormalities are generalized and are usually associated with anemia and neutropenia. These changes present with normal serum levels of iron, ascorbic acid, calcium, phosphorus, and magnesium, as well as with depressed levels of copper and ceruloplasmin. They appear at about three to nine months of age in infants with a low birth weight who are receiving total parenteral nutrition, but can be prevented by greater than normal maintenance levels of copper supplements. Established bone changes improve rapidly after the administration of therapeutic supplements.

Copper↗

PubMed2004

The therapeutic role of taurine in ischaemia-reperfusion injury.

As a non-toxic endogenous antioxidant, the semi-essential amino acid taurine is a potential attenuator of oxidative damage such as that produced by ischaemia-reperfusion injury. Ischaemia-reperfusion injury is a well established if paradoxical phenomenon whereby ischaemic tissue, doomed to necrosis if it is not reperfused, is actually further damaged by oxidative attack when perfusion is restored. This paper is a review of the literature concerning therapeutic strategies in ischaemia-reperfusion injury, including non-pharmacological and pharmacological interventions. There is consistent experimental evidence of an important role of taurine in ischaemia-reperfusion injury, with a clinical role emerging in human trials of taurine administered prior to coronary artery bypass grafting and heart valve surgery.

Animals↗

PubMed2003

Influence of vitamin C on baroreflex sensitivity in chronic heart failure.

Chronic heart failure (CHF) reduces baroreflex sensitivity. Low baroreflex sensitivity, a risk factor for sudden death, could arise partly from CHF-dependent endothelial dysfunction. Vitamin C at high doses has a protective role against CHF-related endothelial damage. This study was conducted to investigate the effect of vitamin C on baroreflex sensitivity in CHF. A study group of 33 subjects with CHF secondary to postischemic dilated cardiomyopathy with an ejection fraction </=35% and a control group (11 subjects) underwent assessment of baroreflex sensitivity by the phenylephrine method and an autonomic nervous system study by power spectral analysis. Variables were assessed after infusion of placebo and high doses of vitamin C (2.5 mg). In subjects with CHF, baroreflex sensitivity was significantly higher after vitamin C than after placebo infusion (placebo: 4.1+/-0.4 versus vitamin C: 5.3+/-0.5 ms/mm Hg, P<0.001). Low-frequency of R-R (LFRR), expressed in normalized units (NU) (P<0.05); LF/high-frequency (HF) ratio (P<0.05), and LF of SBP (LFSBP) decreased significantly; HF power (P<0.05), and alpha-HF (P<0.001) increased. Conversely, in the control group, baroreflex sensitivity and other spectral variables measured at baseline, after placebo, and after vitamin C infusion remained statistically unchanged (placebo: 10.2+/-0.1 versus vitamin C: 10.0+/-0.2 ms/mm Hg, NS). Acute administration of vitamin C at high doses improves baroreflex sensitivity and vagal sinus modulation in patients with CHF. This finding could have notable clinical and therapeutic implications. Key issues to understand are whether the beneficial effect persists during chronic administration and whether it helps to improve survival.

Ascorbic Acid↗

PubMed2005

Use of arsenic trioxide in haematological malignancies: insight into the clinical development of a novel agent.

BACKGROUND: Arsenic trioxide delivers high rates of complete clinical remission in patients with relapsed/refractory acute promyelocytic leukaemia (APL), and is associated with high rates of molecular remission as indicated by PCR negativity for the PML-RARalpha gene. OBJECTIVE: Mitochondria are considered to be the primary intracellular target of arsenic trioxide, and preclinical and mechanistic studies suggest that this agent may have broad applicability in haematological and other malignancies. Investigations of this agent are ongoing in a range of haematological malignancies, and studies in newly diagnosed APL, acute myeloid leukaemia (AML), myelodysplastic syndromes (MDS), multiple myeloma (MM) and chronic myelogenous leukaemia (CML) are reviewed here using published articles and presentations at international congresses to June 2004. Medline was used to source published preclinical and clinical data, and abstract databases and publications from relevant major international haematology/oncology congresses were searched to source updates of preclinical and clinical trial data. FINDINGS: Accumulating data indicate that arsenic trioxide may be a useful addition to the therapeutic regimens that have been so successful in treating newly diagnosed APL, and investigations are ongoing to incorporate this agent into the first-line APL treatment paradigm. Preliminary data from clinical studies indicate that arsenic trioxide has clinical activity as a single agent in MDS and MM, and combination therapies are being investigated. In MM, the combination regimens under study incorporate ascorbic acid, which can enhance the efficacy of arsenic trioxide by reducing intracellular glutathione concentrations. In CML, arsenic trioxide is being investigated in combination with imatinib mesylate in patients who have failed initial imatinib treatment. In AML, although results with single-agent arsenic trioxide were not encouraging, treatment using arsenic trioxide in combination with ascorbic acid is a proposed strategy in elderly patients not able to withstand intensive chemotherapy. CONCLUSION: This versatile agent has a predictable and manageable safety profile and avoids many of the severe toxicities associated with conventional chemotherapies. Ongoing clinical studies will help to define the role of arsenic trioxide in the treatment of haematological malignancies.

Antineoplastic Agents↗

PubMed1989

[The pathogenetic treatment of age-related macular dystrophies].

The paper analyses results after medicamentous treatment of 181 patients with senile macular dystrophies, using methods of pharmacologic correction of sympathetic-adrenal (phosphaden, pyridoxine, ethymisole, ascorbic acid), callicreine-kinin (andecaline, paramidine, cinnarisine) activities and methods of traditional therapy consisting of vasodilative, antisclerotic preparations, vitamins and biostimulants. The comparative analysis has shown that the above preparations normalize KA metabolism and processes of kininogenesis. Stabilization of the dystrophic process is achieved in 82.6% of cases as compared with 71.4% of patients treated by traditional methods; the duration of the therapeutic effect after one course of treatment increases by 3-4 months; the incidence of appearance of transudative-hemorrhagic changes in the central segments of the eye fundus in the presence of atrophic dystrophies of the retina decreases by three times.

Adult↗