Acute and sustained effects of dihydropyridine-type calcium channel antagonists on oxidative stress in systemic sclerosis.
OBJECTIVE
To evaluate the potential antioxidant properties of dihydropyridine calcium channel antagonists in systemic sclerosis.


METHODS
Forty-two patients with systemic sclerosis were included (mean [+/- SD] age, 54 +/- 12 years; mean disease duration, 8 +/- 7 years). Plasma markers of oxidative stress (carbonyl residues, advanced oxidation protein products, malondialdehyde, nitrosothiols, and total thiol groups) were determined 72 hours after the discontinuation of usual dihydropyridine treatment (with either nifedipine or nicardipine), shortly after reinitiation of treatment, and 9 to 12 months later (long-term treatment) in 19 of the patients. Baseline values were compared with those in 23 healthy volunteers.


RESULTS
Mean levels of plasma markers of oxidative stress were much higher in patients with systemic sclerosis than in controls (carbonyls, 0.4 +/- 0.1 nmol/mg protein vs. 0.3 +/- 0.1 nmol/mg protein, P = 0.0001; advanced oxidation protein products, 111 +/- 13 micromol/L vs. 47 +/- 7 micromol/L, p = 0.003; malondialdehyde, 11.3 +/- 3.3 micromol/L vs. 5.5 +/- 1.3 micromol/L, P <0.0001; nitrosothiols, 1.6 +/- 0.2 micromol/L vs. 0.6 +/- 0.2 micromol/L, P <0.0001). In contrast, thiol levels were lower in systemic sclerosis patients (264 +/- 80 micromol/L vs. 435 +/- 50 micromol/L, P <0.0001). Short-term treatment led to a significant decrease in oxidative stress markers (carbonyls, 0.3 +/- 0.1 nmol/mg protein, P <0.0001), advanced oxidation protein products (60 +/- 3 micromol/L, P <0.0001), malondialdehyde (8.8 +/- 5.6 micromol/L, p = 0.0002), and nitrosothiols (1.4 +/- 0.2 micromol/L, p = 0.0001), but an increase in thiol levels (340 +/- 84 micromol/L, P <0.0001). These decreases persisted with long-term treatment.


CONCLUSIONS
Dihydropyridines significantly decrease oxidative stress in systemic sclerosis patients, in both the short and long term.
Allanore
Yannick
Y
Rheumatology A Departments, Paris V University, Assistance Publique Hôpitaux de Paris, Cochin Hospital, Paris, France.
Borderie
Didier
D
Lemaréchal
Hervé
H
Ekindjian
Ohvanesse Garabed
OG
Kahan
André
A
D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D012595:Scleroderma, Systemic / Q000097:blood* / Q000188:drug therapy*; D013438:Sulfhydryl Compounds / Q000097:blood; D013997:Time Factors
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D013438:Sulfhydryl Compounds; D008315:Malondialdehyde; C038806:1,4-dihydropyridine