ascorbic-acid and Raynaud-Disease

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

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

Patients with Raynaud's syndrome have abnormal digital vasoconstriction, which may be secondary to impaired synthesis of, or impaired sensitivity to, nitric oxide. We studied the effect on microcirculation of a nitric-oxide-generating system applied topically to the finger and forearm of healthy volunteers and patients with primary Raynaud's syndrome.. We did a single-blind, randomised, placebo controlled, cross-over study of the microcirculatory response to topical application of a nitric-oxidegenerating gel in 20 patients with severe Raynaud's syndrome, and ten healthy volunteers. We prepared the nitric-oxide-generating system by mixing a solution of KY jelly and sodium nitrite (5% weight/volume), with a solution of KY jelly and ascorbic acid (5% weight/volume). About 0.5 mL of each solution was separately applied to the skin of the forearm (3 cm2), and then mixed with a sterile cotton bud. A similar procedure was done simultaneously on the other arm with KY jelly only (placebo). The procedure was then repeated on the finger pulps. Changes in skin microcirculatory volume and flux were measured bilaterally by infrared photoplethysmography and laser doppler fluxmetry, respectively.. In the forearm, blood flow increased significantly after application of the active gel both in patients with Raynaud's syndrome (microcirculatory volume from mean area under the curve 98 [SE 14] to 1024 [130]; microcirculatory flux from 5060 [462] to 74,800 [3940]) and in healthy controls (volume from 85 [19] to 1020 [60]; flux from 4420 [435] to 84,500 [7000]). In the fingers, although baseline blood flow was lower in patients than in controls, both groups showed increases with application of active gel (volume from 1100 [194] to 3280 [672] and 2380 [441] to 6160 [1160], respectively; flux from 33,400 [4200] to 108,000 [13,600] and 52,000 [8950] to 185,000 [19,500]). Increases in blood flow with placebo gel were not significant. No adverse effects were reported.. In primary Raynaud's syndrome, topical application of a nitric-oxide-generating system can stimulate an increase in both microcirculatory volume and flux.

Topics: Administration, Topical; Adolescent; Adult; Ascorbic Acid; Blood Flow Velocity; Blood Volume; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Fingers; Forearm; Humans; Laser-Doppler Flowmetry; Male; Microcirculation; Middle Aged; Nitric Oxide; Photoplethysmography; Raynaud Disease; Single-Blind Method; Skin; Sodium Nitrite

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

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