title: Arginines Plasma Concentration and Oxidative Stress in Mild to Moderate COPD.
abstract: BACKGROUND
  Elevated plasma concentrations of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) have been observed in respiratory conditions such as asthma and cystic fibrosis. Since oxidative stress has been shown to increase the activity of arginine methylating enzymes, hence increased ADMA synthesis, and to reduce ADMA degrading enzymes, hence increased ADMA concentrations, we assessed methylated arginines concentrations in chronic obstructive pulmonary disease (COPD), a disease characterized by increased oxidative stress.
  
  
  METHODS
  Plasma arginine, ADMA and symmetric dimethylarginine (SDMA), oxidative stress markers (thiobarbituric acid reactive substances, TBARS, and plasma proteins SH, PSH) and antioxidants (taurine and paraoxonase 1, PON1, activity) were measured in 43 COPD patients with mild (n = 29) or moderate (n = 14) disease and 43 age- and sex-matched controls.
  
  
  RESULTS
  TBARS significantly increased with COPD presence and severity (median 2.93 vs 3.18 vs 3.64 μmol/L, respectively in controls, mild and moderate group, p<0.0001 by ANOVA) whereas PSH decreased (6.69±1.15 vs 6.04±0.85 vs 5.33±0.96 μmol/gr prot, p<0.0001 by ANOVA). Increased ADMA/arginine ratio, primarily due to reduced arginine concentrations, was also observed with COPD presence and severity (median 0.0067 vs 0.0075 vs 0.0100, p<0.0001 by ANOVA). In multiple logistic regression analysis, only TBARS (OR 0.44, 95% CI 0.25-0.77; p = 0.0045) and ADMA/Arginine ratio (OR 1.72, 95% CI 2.27-13.05; p = 0.02) were independently associated with COPD severity.
  
  
  CONCLUSIONS
  COPD presence and severity are associated with increased oxidative stress and alterations in arginine metabolism. The reduced arginine concentrations in COPD may offer a new target for therapeutic interventions increasing arginine availability.
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Zinellu
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
authors.forename: Alessandro Giuseppe
authors.initials: AG
authors.lastname: Fois
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sotgia
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Sotgiu
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Zinellu
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Bifulco
authors.affiliation: Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, Australia.
authors.forename: Arduino A
authors.initials: AA
authors.lastname: Mangoni
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Pirina
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.|Quality Control Unit, University Hospital Sassari (AOU), Sassari, Italy.
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Carru
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood*; D043303:Aryldialkylphosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology*; D012720:Severity of Illness Index; D012737:Sex Factors; D013654:Taurine / Q000097:blood
chemical_list: D015415:Biomarkers; D013654:Taurine; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human