title: Probucol improves symptoms and reduces lipoprotein oxidation susceptibility in patients with Raynaud's phenomenon.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Academic Unit of Rheumatology, Royal Free Hospital School of Medicine, London, UK.
authors.forename: C P
authors.initials: CP
authors.lastname: Denton
authors.forename: T D
authors.initials: TD
authors.lastname: Bunce
authors.forename: M B
authors.initials: MB
authors.lastname: Dorado
authors.forename: Z
authors.initials: Z
authors.lastname: Roberts
authors.forename: H
authors.initials: H
authors.lastname: Wilson
authors.forename: K
authors.initials: K
authors.lastname: Howell
authors.forename: K R
authors.initials: KR
authors.lastname: Bruckdorfer
authors.forename: C M
authors.initials: CM
authors.lastname: Black
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000097:blood; D015331:Cohort Studies; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood; D009543:Nifedipine / Q000008:administration & dosage; D010084:Oxidation-Reduction; D011341:Probucol / Q000008:administration & dosage*; D011928:Raynaud Disease / Q000188:drug therapy* / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014665:Vasodilator Agents / Q000008:administration & dosage; D014810:Vitamin E / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D000975:Antioxidants; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D014280:Triglycerides; D014665:Vasodilator Agents; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D009543:Nifedipine; D011341:Probucol; D001205:Ascorbic Acid