title: Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age-related macular degeneration.
abstract: BACKGROUND
  Nitric oxide (NO), hydroxyl radical (OH*), superoxide anion (O2-) and hydrogen peroxide (H2O2) are free-radicals released in oxidative stress. Superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT) are antioxidant enzymes, mediating defense against oxidative stress. Excess NO and/or defective antioxidants cause lipid peroxidation, cellular dysfunction and death. Age-related maculopathy (ARM) or degeneration (ARMD) is the leading cause of irreversible blindness in developed countries. The etiology is unclear and the molecular factors contributing this disease remain to be specified.
  
  
  OBJECTIVE
  This multicenter, double-blind, cross-sectional study aimed to investigate plasma NO and lipid peroxidation levels with relation to antioxidant enzyme activities in erythrocyte and plasma of patients with ARMD compared with healthy control subjects.
  
  
  METHODS
  NO, lipid peroxidation (measured as plasma malondialdehyde [MDA] levels) and the catalytic activity of SOD, GSHPx and CAT were measured in a group of 41 patients with maculopathy (19 men, 22 women; 67.12 +/- 3.70 years) and compared with 25 age- and sex-matched healthy control subjects without maculopathy (12 men, 13 women; 68.04 +/- 3.02 years). NO and MDA levels were measured in plasma, CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Color fundus photographs were used to assess the presence of maculopathy, and the patients were divided into two groups using clinical examination and grading of photographs; early-ARM (n = 22) and late-ARMD (n = 19).
  
  
  RESULTS
  All patients with maculopathy had significantly (p < 0.001) higher plasma NO levels over control subjects (mean +/- SD, 48.58 +/- 8.81 vs. 28.22 +/- 3.39 micromol/l). Plasma MDA levels in patients and control subjects were 4.99 +/- 1.00 and 2.16 +/- 0.24 micromol/l, respectively, and the difference was significant (p < 0.001). On the other hand, SOD and GSHPx activities were significantly lower in both RBCs and plasma of patients with maculopathy than in control subjects (RBCs-SOD, 3509.30 +/- 478.22 vs. 5033.30 +/- 363.98 U/g Hb, p < 0.001; plasma-SOD, 560.95 +/- 52.52 vs. 704.76 +/- 24.59 U/g protein, p < 0.001; RBCs-GSHPx, 663.43 +/- 41.74 vs. 748.80 +/- 25.50 U/g Hb, p < 0.001; plasma-GSHPx, 98.26 +/- 15.67 vs. 131.80 +/- 8.73 U/g protein, p < 0.001). RBCs-CAT levels were not different between groups (131.68 +/- 12.89 vs. 133.00 +/- 13.29 k/g Hb, p = 0.811). Late-ARMD patients had significantly lower antioxidant enzyme levels and higher MDA levels when compared with early-ARM patients (for each, p < 0.001). In addition, plasma NO and MDA levels were negatively correlated with SOD and GSHPx activities.
  
  
  CONCLUSIONS
  This study demonstrated for the first time that NO, the most abundant free-radical in the body, might be implicated in the pathophysiology of ARMD in association with decreased antioxidant enzymes and increased lipid peroxidation status.
authors.affiliation: Department of Ophthalmology, Erciyes University Medical Faculty, Kayseri, Turkey. evereklioglu@hotmail.com
authors.forename: Cem
authors.initials: C
authors.lastname: Evereklioglu
authors.forename: Hamdi
authors.initials: H
authors.lastname: Er
authors.forename: Selim
authors.initials: S
authors.lastname: Doganay
authors.forename: Mustafa
authors.initials: M
authors.lastname: Cekmen
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Turkoz
authors.forename: Baris
authors.initials: B
authors.lastname: Otlu
authors.forename: Elif
authors.initials: E
authors.lastname: Ozerol
mesh_terms: D000368:Aged; D000975:Antioxidants; D002374:Catalase / Q000097:blood*; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood*; D006801:Humans; D015227:Lipid Peroxidation; D008268:Macular Degeneration / Q000201:enzymology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000097:blood*
chemical_list: D000975:Antioxidants; D009569:Nitric Oxide; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase