ascorbic-acid and Scleroderma--Systemic

The purpose of this study is to clarify the relationship between systemic sclerosis (SSC) and oxidative stress markers in blood.. We conducted a systematic literature search of databases, including PubMed and Embase, for studies reporting circulating oxidative stress markers in patients with SSC and controls published from 1980 to December 2015. Standardized mean differences (SMDs) and 95% confidence intervals (95%CI) were calculated.. Of the 1076 articles initially retrieved, 47 were included in our meta-analysis including 12 oxidative stress markers. The concentrations of nitric oxide (SMD = 0.77; 95%CI: 0.18, 1.36; p = 0.01), malondialdehyde (SMD =1.63; 95%CI: 1.03, 2.24; p = 0.000), asymmetric dimethylarginine (SMD = 0.51; 95%CI: 0.12, 0.91; p = 0.011), and ROOH (SMD = 3.37; 95%CI: 0.28, 6.46; p = 0.033) in the blood of patients with SSC were higher than those of the control group, whereas the concentrations of superoxide dismutase (SMD = -1.11; 95%CI: -1.57, -0.65; p = 0.000) and vitamin C (SMD = -1.12; 95%CI: -1.51, -0.73; p = 0.000) were lower than in the control group.. The oxidative stress markers in blood for patients with SSC were aberrant, indicating the imbalanced states of oxidation and antioxidation in SSC.

Topics: Arginine; Ascorbic Acid; Biomarkers; Case-Control Studies; Humans; Malondialdehyde; Nitric Oxide; Oxidative Stress; Scleroderma, Systemic; Superoxide Dismutase

Oxidative stress, favoring disease progression by a rapid degeneration of endothelial cell function is deeply involved in Systemic Sclerosis (SSc) pathogenesis. Raynaud's phenomenon (RP), present in 90% of patients with SSc, provoking frequent daily episodes of hypoxia-reperfusion injury, produces several episodes of free radicals-mediated endothelial derangement. These events results in a positive feedback effect of luminal narrowing and ischemia and therefore to the birth of a vicious cycle of oxygen free radicals (OFR) generation, leading to endothelial damage, intimal thickening and fibrosis. Thus ischemia and reperfusion are two criticals events that may induce oxidative stress and inactivation of antioxidant enzymes. In RP and SSc, a reduced concentration of ascorbic acid, alpha-tocopherol and beta-carotene as well as low values of Selenium have been reported. This antioxidative potential deficiency increases the propensity to oxidative stress. favoring the development of injury mediated by OFR. We reviewed several antioxidant compounds, aiming at their capacity of reverting endothelial dysfunction and damage, scavenging lipid peroxidation and reducing multiple episodes of hypoxia-reperfusion injury. In order to interrupt SSc vicious cycle, we propose a main strategy for SSc treatment by a supplementation of antioxidants and different kind of drugs with antioxidant property, such as Lazaroids, Resveratrol, Melatonin and Probucol.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Endothelium, Vascular; Humans; In Vitro Techniques; Melatonin; Nitric Oxide; Oxidative Stress; Pregnatrienes; Probucol; Raynaud Disease; Reactive Oxygen Species; Reperfusion Injury; Resveratrol; Scleroderma, Systemic; Selenium; Stilbenes; Vitamin E

Topics: Adolescent; Adult; Ascorbic Acid; Cells, Cultured; Collagen; Culture Media; Female; Fibroblasts; Humans; Hydroxyproline; Male; Middle Aged; Scleroderma, Systemic; Skin; Time Factors

Previous studies have shown that patients with Raynaud's phenomenon secondary to systemic sclerosis present abnormal endothelial function; the mechanisms responsible for the endothelial dysfunction are unknown but increased vascular oxidative stress could be a possible cause. The hypothesis that a potent water-soluble antioxidant can reverse endothelial dysfunction in these patients was tested in the present study. We examined 11 female patients with Raynaud's phenomenon secondary to systemic sclerosis and ten healthy control women by ultrasound imaging of the brachial artery to assess flow-mediated (endothelium-dependent) and nitrate-induced (endothelium-independent) vasodilatation. Flow-mediated dilatation and nitrate-induced dilatation were significantly reduced in patients with Raynaud's phenomenon, indicating abnormal endothelial and smooth muscle cell function. Patients with Raynaud's phenomenon entered a double-blind, randomized, crossover placebo-controlled trial and received orally 2 g of ascorbic acid or placebo; vascular studies were repeated two hours after ascorbic acid or placebo administration. Flow-mediated dilatation did not improve after ascorbic acid (1.6 +/- 2.2% to 2.2 +/- 2.5%, ns) or placebo administration (1.2 +/- 1.9% to 1.7 +/- 1.4%, ns); also nitrate-induced dilatation was similar after ascorbic acid or placebo (16 +/- 7.4% vs 17 +/- 8%, ns), suggesting no effect of ascorbic acid on endothelial and vascular smooth muscle function. In conclusion, ascorbic acid does not reverse endothelial vasomotor dysfunction in the brachial circulation of patients with Raynaud's phenomenon secondary to systemic sclerosis. The use of different antioxidants or different dosing of ascorbic acid may be required to show a beneficial effect on endothelial vasodilator function.

Topics: Administration, Oral; Adult; Aged; Antioxidants; Ascorbic Acid; Brachial Artery; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Female; Humans; Middle Aged; Oxidative Stress; Raynaud Disease; Scleroderma, Systemic; Ultrasonography; Vasodilation

Reactive oxygen species have been implicated in the pathogenesis of inflammatory and vascular disease. We have undertaken a controlled trial to evaluate probucol, a synthetic antioxidant, as a potential therapy for Raynaud's phenomenon.. The study cohort included patients with systemic sclerosis (SSc; n = 20), primary Raynaud's phenomenon (n = 15) or 'autoimmune Raynaud's' (n = 5). Patients were allocated to receive either probucol (500 mg daily) or nifedipine (20 mg daily) for 12 weeks. Clinical and biochemical variables at baseline were compared with those at completion of treatment. Evaluation included assessment of Raynaud's attack frequency and severity by visual analogue scale, measurement of low-density lipoprotein (LDL) oxidation lag time, and plasma concentrations of cholesterol, triglyceride, vitamin E and vitamin C.. There was a significant reduction of both the frequency and severity of Raynaud's attacks in the patients who received probucol, but not in the control group. LDL oxidation lag time, reflecting in vitro susceptibility to oxidation, was also increased by probucol therapy and serum cholesterol levels were significantly reduced. Similar changes were observed in both SSc- and non-SSc-associated Raynaud's cases.. These data suggest that probucol may be useful for the symptomatic treatment of Raynaud's phenomenon and also reduces LDL oxidation susceptibility. Since oxidized lipoproteins may mediate vascular damage in SSc, the use of probucol could have additional disease-modifying benefits. Based upon the results of this pilot study, further evaluation of this novel form of therapy is warranted.

Topics: Anticholesteremic Agents; Antioxidants; Ascorbic Acid; Cohort Studies; Humans; Lipoproteins; Lipoproteins, LDL; Nifedipine; Oxidation-Reduction; Probucol; Raynaud Disease; Scleroderma, Systemic; Triglycerides; Vasodilator Agents; Vitamin E

Nitric oxide ((.-)NO) is an important physiological signaling molecule and potent vasodilator. Recently, we have shown abnormal (.-)NO metabolism in the plasma of patients with systemic sclerosis (SSc), a disease that features excessive collagen overproduction as well as vascular dysfunction. The current study investigates the effects of (.-)NO and peroxynitrite (ONOO(-)) on secretion of type I collagen by SSc dermal fibroblasts, compared with those from normal dermal fibroblasts (CON) and a dermal fibroblast cell line (AG). Dermal fibroblasts were incubated with (.-)NO donors (SNP, DETA-NONOate) with or without the antioxidant ascorbic acid, or ONOO(-) for 24-72 h. In CON and AG fibroblasts, type I collagen was dose dependently decreased by SNP or DETA-NONOate. However, (.-)NO had no effect in SSc fibroblasts. Furthermore, the inhibition of collagen synthesis by (.-)NO was reversed by ascorbic acid and was not affected by 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanyl cyclase, or 8-bromoguanosine cyclic 3',5'-monophosphate, a cGMP agonist. SNP also showed a significant up-regulation of matrix metalloproteinase-1 (MMP-1) protein and activity levels, an essential collagenase involved in collagen degradation, in the AG fibroblasts. Additionally, (.-)NO-treated fibroblasts had lower prolyl hydroxylase activity, an enzyme important in the post-translational processing of collagen, while there was no effect on total protein levels. There were no significant effects on type I collagen levels when dermal fibroblasts were treated with ONOO(-). Taken together, ()NO inhibits collagen secretion in normal dermal fibroblasts but regulation is lost in SSc fibroblasts, while ONOO(-) itself is ineffective. (.-)NO inhibition of collagen was by cGMP-independent regulatory mechanisms and in part may be due to up-regulation of MMP-1 and/or inhibition of prolyl hydroxylase. These differences may contribute to the observed pathology of SSc.

Topics: Ascorbic Acid; Cell Survival; Collagen Type I; Fibroblasts; Humans; Kinetics; Nitric Oxide; Nitroprusside; Peroxynitrous Acid; Potassium Cyanide; Scleroderma, Systemic; Skin

To investigate whether reduced circulating levels of ascorbic acid in patients with systemic sclerosis (SSc) are a result of malabsorption.. Eight patients with SSc, but with no evidence of bacterial overgrowth, and 8 healthy controls were recruited. On the first day of study, each subject was given orally an aliquot of [14C] ascorbic acid, which was then "flushed out" by oral intake of unlabeled ascorbic acid for the following 7 days. Plasma samples were collected at specified intervals and urine was collected continuously over the 8 day study period. [14C] content of plasma and urine were measured by scintillation counting. For each subject, a plasma [14C] decay curve was drawn. Each subject's ascorbic acid absorption was assessed using the area under the curve (AUC) and the apparent renal clearance (CLr[app]). Ascorbic acid intake was assessed using dietary history and food composition tables.. There were no differences in the dietary intake of vitamin C (p = 0.16) and body mass indices (p = 0.91) between patients and controls. The plasma [14C] AUC and CLr(app) were similar between patients and controls [AUC patient mean (standard deviation, SD) = 37.1 (6.8), AUC control mean (SD) = 38.6 (9.9), p = 0.74; CLr(app) patient mean (SD) = 0.57 (0.24), CLr(app) control mean (SD) = 0.47 (0.27), p = 0.45].. There was no evidence of impaired absorption of ascorbic acid in patients with SSc without bacterial overgrowth compared to healthy controls.

Topics: Absorption; Adult; Ascorbic Acid; Body Mass Index; Carbon Radioisotopes; Female; Gastrointestinal Motility; Humans; Intestines; Malabsorption Syndromes; Male; Middle Aged; Scleroderma, Systemic

To document habitual intakes of micronutrient antioxidants in patients with systemic sclerosis (SSc) in light of studies reporting subnormal levels of ascorbate and selenium in this patient group.. Dietary intakes of vitamin C, selenium, alpha-tocopherol, beta-carotene, and sulfur amino acid precursors of glutathione were assessed using the 7 day weighed record in 12 patients with SSc and in 12 healthy control subjects. The intakes of the first 4 substances were examined in relation to plasma/serum levels, while intakes of sulfur amino acids were examined in relation to urinary inorganic sulfate.. Antioxidant and sulfur amino acid intakes were similar in patients and controls, although the patients had lower levels of selenium (median 74 compared to 87 milligrams in controls; p = 0.014) and of vitamin C in plasma (median 6.0 compared to 11.1 milligrams/l in controls; p = 0.08). Inorganic sulfate concentration in urine was similar in patients and controls.. Our results suggest that reduced blood levels of the water soluble antioxidants selenium and ascorbic acid in patients with SSc are not due to dietary deficiency. Other explanations must therefore be sought.

Topics: Adult; Aged; Amino Acids, Sulfur; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Creatinine; Diet; Energy Intake; Female; Humans; Male; Micronutrients; Middle Aged; Scleroderma, Systemic; Selenium; Smoking; Sulfates; Vitamin E

To examine the resistance to oxidation of low-density lipoproteins (LDL) from patients with systemic sclerosis (SSc) and primary Raynaud's phenomenon (RP) compared with healthy controls.. Plasma LDL were isolated from patients with diffuse cutaneous and limited cutaneous SSc (dcSSc and lcSSc, respectively), patients with primary RP, and healthy control subjects. The lipoproteins were assessed for their resistance to oxidation in the presence of cupric ions, using spectrophotometric assays.. LDL from patients with dcSSc and lcSSc were more susceptible to oxidation than were those from healthy control subjects or patients with RP.. Our findings suggest that free radicals may play a role in the pathology of SSc.

Topics: Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cholesterol; Fatty Acids; Female; Humans; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Raynaud Disease; Scleroderma, Systemic; Triglycerides; Vitamin E

Topics: Analysis of Variance; Antioxidants; Ascorbic Acid; Cholesterol; Chromatography, High Pressure Liquid; Humans; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Scleroderma, Localized; Scleroderma, Systemic; Triglycerides; Vitamin E

Scleroderma is a fibrotic disorder of unknown etiology that is characterized by excessive collagen synthesis and its deposition in the skin and various internal organs.. To examine whether an overproduction of extracellular matrix molecules is a result of either increased fibroblast proliferation or increased collagen synthesis. As results of clinical trials with 1,25-dihydroxyvitamin D3 (calcitriol) have suggested beneficial effect in the treatment of scleroderma patients, the effects of calcitriol on fibroblasts derived from scleroderma and normal skin has been examined as well.. Cultures of fibroblasts were established from biopsies from involved and uninvolved skin of scleroderma patients and from skin of healthy subjects, and compared with respect to proliferation, collagen synthesis and collagen lattice contraction.. No significant differences in cell proliferation and in the extent of fibroblast-induced collagen lattice contraction have been found between scleroderma patients exhibited a disorganized growth pattern in a monolayer culture in contrast to normal fibroblasts. Collagen synthesis tends to be higher in scleroderma fibroblasts as compared with controls. Calcitriol exerted an antiproliferative and antisynthetic effect on fibroblasts, which, however, did not discriminate healthy fibroblasts from fibroblasts derived from involved or uninvolved scleroderma plaques.. Our findings suggest that collagen accumulation may not result from increased proliferation or altered dynamic properties of fibroblasts in a scleroderma lesion but from increased collagen biosynthesis. We additionally found that calcitriol does not selectively affect scleroderma fibroblasts.

Topics: Adult; Aged; Ascorbic Acid; Biopsy; Calcitriol; Carbon Radioisotopes; Cell Division; Cells, Cultured; Collagen; Dose-Response Relationship, Drug; Extracellular Matrix; Female; Fibroblasts; Humans; Male; Middle Aged; Proline; Scleroderma, Localized; Scleroderma, Systemic; Skin

To investigate the possibility that micronutrient antioxidant status is an important factor in determining the severity of Raynaud's phenomenon (RP) and in differentiating between patients with primary Raynaud's phenomenon (PRP) and those in whom Raynaud's is secondary to systemic sclerosis (SSc).. Four micronutrient antioxidants (selenium, vitamin E, beta-carotene and ascorbic acid) and 2 "markers" of free radical associated activity were assayed in peripheral blood from 10 patients with PRP, 9 with limited cutaneous SSc (ISSc), 9 with diffuse SSc (dSSc) and 15 healthy control subjects.. Plasma ascorbic acid was reduced in all 3 groups of patients: median level 10.6 mg/l in controls, 4.8 mg/l in PRP (p < 0.01), 2.5 mg/l in ISSc (p < 0.01) and 6.8 mg/l in dSSc (p < 0.05). A reduction in serum selenium was especially found in dSSc (median 75 micrograms/l compared to 100 micrograms/l in controls, p < 0.05). In keeping with these deficiencies, the serum concentration of 9, 11, linoleic acid was elevated in RP patients: median values for the molar ratio of the isomer to the parent fatty acid were 1.91% in controls, 3.70% in ISSc (p < 0.05) and 3.85% in dSSc (p < 0.01). Smoking patients showed lower levels of ascorbic acid and higher levels of the linoleic isomer than nonsmokers.. Deficiencies of ascorbic acid and selenium may predispose towards irreversible tissue injury in RP patients and cigarette smoke may be an independent risk factor. Micronutrient antioxidant supplements may be of therapeutic value.

Topics: Aging; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Female; Free Radicals; Humans; Male; Raynaud Disease; Scleroderma, Systemic; Selenium; Sex Factors; Smoking; Trace Elements; Vitamin E

Topics: Adolescent; Adult; Aged; Amyloidosis; Arthritis, Juvenile; Arthritis, Rheumatoid; Ascorbic Acid; Child; Child, Preschool; Dimethyl Sulfoxide; Drug Evaluation; Glomerular Filtration Rate; Humans; Kidney; Middle Aged; Proteinuria; Scleroderma, Systemic; Sjogren's Syndrome; Ultrasonics

Topics: Ascorbic Acid; Cells, Cultured; Collagen; Fibroblasts; Humans; Scleroderma, Systemic

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Diet Therapy; Female; Humans; Leukocyte Count; Male; Scleroderma, Systemic; Scurvy; Skin Tests

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Parasympatholytics; Scleroderma, Systemic

Topics: Ascorbic Acid; Collagen Diseases; Corrinoids; Cystitis; Cystitis, Interstitial; Drug Therapy; Humans; Lupus Erythematosus, Systemic; Pyridoxine; Scleroderma, Systemic; Ulcer; Vitamin B 12