ascorbic-acid and Hepatolenticular-Degeneration

Topics: Anemia; Animals; Ascorbic Acid; Ceruloplasmin; Chelating Agents; Copper; Endoplasmic Reticulum; Hemoglobins; Hepatolenticular Degeneration; Humans; Iron; Kinetics; Models, Biological; Models, Chemical; Oxidoreductases; Transferrin

Oxidative stress has been reported in Wilson's disease with neurological manifestation (WDNM), but there is a paucity of studies on the role of adjunctive antioxidant therapy. This study aims to evaluate the efficacy of adjunctive vitamin C and E treatment in reducing oxidative stress and improving clinical outcomes. Forty-nine patients with WDNM were included and their clinical details were noted. Glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured using spectrophotometer at baseline and follow-up. All patients received zinc with or without chelating therapy, and 32 of them prescribed vitamin C (500 mg/day) and E (400 mg/day). Clinical outcomes at 6, 12, and 24 months were categorized as improved, static, or worsened based on improvement in Burke-Fahn-Marsden (BFM) score (>10%) and/or severity grade (> 1). Baseline parameters were similar between two groups; except BFM score was higher in the antioxidant group. At follow-up, the antioxidant group had higher GSH, TAC, and lower MDA levels compared with baseline. Patients on antioxidant treatment experienced improvement more frequently at 6 (53.1% vs. 29.4%), 12 (62.5% vs. 29.4%), and 24 months (68.8% vs. 35.3%) compared with those without antioxidant treatment. In WDNM, adjunctive vitamin C and E treatment reduce oxidative stress and improve clinical outcome.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Chelating Agents; Child; Drug Combinations; Female; Glutathione; Hepatolenticular Degeneration; Humans; Male; Malondialdehyde; Penicillamine; Vitamin E; Vitamins; Zinc

Defective copper excretion in Wilson's disease can result in increased neurological copper concentrations. This is thought to occur following exposure to increased circulating copper released from necrotic hepatocytes in a saturated liver. BU17 human glioma cells and SH-SY5Y human neuroblastoma cells were exposed to media supplemented with copper in the range 0-250 microM for periods up to 48 h to investigate this hypothesis. Copper uptake, cell growth, intracellular radical generation, and oxidative stress were measured in copper exposed cells. No increase in copper uptake or inhibition of cell growth could be measured in either cell type at any time point or copper concentration investigated. However, significant increases in radical generation (p < 0.001) could be measured in both BU17 and SH-SY5Y cells. A decreased ability to cope when the cells were exposed to additional pro-oxidants suggested that the cells were under oxidative stress with significant reductions in cell viability following exposure to both copper and ascorbic acid. These data suggest that copper sequestration does not occur in neuronal cells exposed to elevated extracellular copper concentrations.

Topics: Antioxidants; Ascorbic Acid; Cell Division; Copper; Dose-Response Relationship, Drug; Free Radicals; Hepatolenticular Degeneration; Humans; Intracellular Fluid; Neuroglia; Neurons; Oxidation-Reduction; Oxidative Stress; Tumor Cells, Cultured

It has been demonstrated that the level of serum copper unbound to ceruloplasmin (loosely bound copper) is increased in Wilson's disease, although the total serum copper concentration is usually low, reflecting a low ceruloplasmin level. To assess the contribution of free radical reactions catalyzed by nonceruloplasmin copper to the development of complications in this disease, we investigated copper and antioxidant status in four untreated patients who had hepatic dysfunction with or without hemolytic anemia and made a comparison with five patients controlled on penicillamine therapy and 19 age-matched healthy children. We found that loosely bound copper in plasma measured by the phenanthroline assay was detectable in three of four untreated patients with Wilson's disease, but was not detectable in the patients during therapy or in the healthy controls. Among the various antioxidants, the ascorbate and urate levels were markedly reduced before treatment (mean +/- SD, 23 +/- 16 microM for ascorbate and 90 +/- 59 microM for urate) compared with the values in the patients during treatment with penicillamine (67 +/- 19 and 302 +/- 78 microM, p < 0.05) and in control children (60 +/- 8 and 254 +/- 48 microM, p < 0.05). We also demonstrated that the plasma concentration of allantoin, an oxidation product of uric acid and a possible marker of radical generation in vivo, was markedly elevated in the untreated patients (11.0 +/- 1.8 versus 4.3 +/- 0.5 microM in patients on therapy and 6.5 +/- 0.8 microM in controls, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Allantoin; Antioxidants; Ascorbic Acid; Biomarkers; Ceruloplasmin; Child; Copper; Female; Free Radicals; Hepatolenticular Degeneration; Humans; Male; Penicillamine; Thiobarbituric Acid Reactive Substances; Uric Acid; Vitamin E

Zinc (Zn) is increasingly being used as a treatment for Wilson's disease. Some physicians have been prescribing Zn in conjunction with other anticopper agents, such as penicillamine or trien, although theoretically these drugs might be antagonistic in their effects. In addition, Wilson's disease patients quite often take vitamin C in high doses in conjunction with Zn therapy, and there are indications of possible interactions among vitamin C, Zn and copper (Cu). Interactions of penicillamine, trien, and vitamin C with Zn have not been previously studied in terms of the potential effects of these agents on Zn efficacy in Wilson's disease. Here we have studied these interactions in the maintenance phase of therapy, using Cu balance and absorption of orally administered 64Cu as endpoints. We find evidence for probable interactions of both penicillamine and trien with Zn; however, the end result on Cu balance is about the same with Zn alone as it is with Zn plus one of the other agents. Thus, there appear to be no advantages to concomitant administration. We find no detectable interaction of Zn and vitamin C on Cu balance, when vitamin C is taken in daily doses of 1000 mg.

Topics: Ascorbic Acid; Copper; Copper Radioisotopes; Drug Interactions; Drug Therapy, Combination; Hepatolenticular Degeneration; Humans; Penicillamine; Trientine; Zinc

Topics: Arthritis, Rheumatoid; Ascorbic Acid; Ceruloplasmin; Chemical Phenomena; Chemistry; Hepatolenticular Degeneration; Humans; Hyaluronic Acid; Synovial Fluid; Viscosity