Arginines Plasma Concentration and Oxidative Stress in Mild to Moderate COPD

Angelo Zinellu, Alessandro Fois, Salvatore Sotgia, Elisabetta Sotgiu, Elisabetta Zinellu, Fabiana Bifulco, Arduino Mangoni, Pietro Pirina, Ciriaco Carru

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    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. Conclusion: 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.

    Original languageEnglish
    Article numbere0160237
    Pages (from-to)Art: e0160237
    Number of pages10
    JournalPLoS One
    Volume11
    Issue number8
    DOIs
    Publication statusPublished - 1 Aug 2016

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    Zinellu, A., Fois, A., Sotgia, S., Sotgiu, E., Zinellu, E., Bifulco, F., Mangoni, A., Pirina, P., & Carru, C. (2016). Arginines Plasma Concentration and Oxidative Stress in Mild to Moderate COPD. PLoS One, 11(8), Art: e0160237. [e0160237]. https://doi.org/10.1371/journal.pone.0160237