Emerging potentials for an antioxidant therapy as a new approach to the treatment of systemic sclerosis.
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.
Simonini
G
G
Department of Pediatrics, University of Florence, Institute of Internal Medicine, Italy.
Pignone
A
A
Generini
S
S
Falcini
F
F
Cerinic
M M
MM
Gabriele
S
S
Alberto
P
P
Sergio
G
G
Fernanda
F
F
Marco
M C
MC
D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D008550:Melatonin / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D011281:Pregnatrienes / Q000627:therapeutic use; D011341:Probucol / Q000627:therapeutic use; D011928:Raynaud Disease / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D000077185:Resveratrol; D012595:Scleroderma, Systemic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012643:Selenium / Q000097:blood; D013267:Stilbenes / Q000627:therapeutic use; D014810:Vitamin E / Q000097:blood; D019207:beta Carotene / Q000097:blood
D000975:Antioxidants; D011281:Pregnatrienes; D017382:Reactive Oxygen Species; D013267:Stilbenes; D019207:beta Carotene; D014810:Vitamin E; D009569:Nitric Oxide; D012643:Selenium; D008550:Melatonin; D011341:Probucol; D001205:Ascorbic Acid; D000077185:Resveratrol; C053355:tirilazad