8-Hydroxy-2’-deoxyguanosine as a biomarker of oxidative stress in acute exacerbation of chronic obstructive pulmonary disease
8-Hydroxy-2’-deoxyguanosine as a biomarker of oxidative stress in acute exacerbation of chronic obstructive pulmonary disease
Background/aim: 8-Hydroxy-2’-deoxyguanosine (8-OHdG) is a biomarker of oxidative stress and has been implicated in manydiseases. The aim of this study was to investigate the clinical value of plasma 8-OHdG level in patients with acute exacerbation of chronicobstructive pulmonary disease (AECOPD).Materials and methods: A total of 154 subjects were enrolled in this study, including 20 healthy volunteers, 24 COPD patients in thestable phase, and 110 AECOPD patients. Peripheral blood samples, demographic information, and clinical characteristics were collectedfrom all subjects at the time of being recruited into the study. Plasma 8-OHdG level was detected by enzyme-linked immunosorbentassay.Results: 8-OHdG was increased in patients with AECOPD compared to healthy subjects and patients with stable COPD, especially insmokers. It also increased with the GOLD stage, mMRC grade, CAT score, and group level of combined COPD assessment. Additionally,further analysis revealed that 8-OHdG was negatively correlated with FEV1, FEV1% predicted, and FEV1/FVC and positively correlatedwith C-reactive protein, procalcitonin, and neutrophil CD64.Conclusion: 8-OHdG is associated with spirometric severity, symptomatic severity, exacerbation risk, and inflammatory biomarkers inAECOPD patients, suggesting it as a promising biomarker for reflecting disease severity and guiding the choice of optimal therapeuticdecision.
___
- 1. Mannino DM, Buist AS. Global burden of COPD: risk factors,
prevalence, and future trends. Lancet 2007; 370: 765-773.
- 2. Celli BR, MacNee W, Force AET. Standards for the diagnosis
and treatment of patients with COPD: a summary of the ATS/
ERS position paper. Eur Respir J 2004; 23: 932-946.
- 3. Budweiser S, Harlacher M, Pfeifer M, Jorres RA. Comorbidities and hyperinflation are independent risk factors of
all-cause mortality in very severe COPD. COPD 2014; 11: 388-
400.
- 4. Miller MR. Multicomponent indices to predict survival in
COPD. Eur Respir J 2014; 43: 1206.
- 5. Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C,
Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura
M et al. Global strategy for the diagnosis, management, and
prevention of chronic obstructive pulmonary disease: GOLD
executive summary. Am J Respir Crit Care Med 2013; 187: 347-
365.
- 6. Almagro P, Soriano JB, Cabrera FJ, Boixeda R, AlonsoOrtiz MB, Barreiro B, Diez-Manglano J, Murio C, Heredia
JL; Working Group on COPD, Spanish Society of Internal
Medicine. Short- and medium-term prognosis in patients
hospitalized for COPD exacerbation: the CODEX index. Chest
2014; 145: 972-980.
- 7. Casadevall C, Coronell C, Ramirez-Sarmiento AL, MartinezLlorens J, Barreiro E, Orozco-Levi M, Gea J. Upregulation
of pro-inflammatory cytokines in the intercostal muscles of
COPD patients. Eur Respir J 2007; 30: 701-707.
- 8. Garcia-Rio F, Miravitlles M, Soriano JB, Munoz L, DuranTauleria E, Sanchez G, Sobradillo V, Ancochea J; EPI-SCAN
Steering Committee. Systemic inflammation in chronic
obstructive pulmonary disease: a population-based study.
Respir Res 2010; 11: 63.
- 9. Papi A, Bellettato CM, Braccioni F, Romagnoli M, Casolari P,
Caramori G, Fabbri LM, Johnston SL. Infections and airway
inflammation in chronic obstructive pulmonary disease severe
exacerbations. Am J Respir Crit Care Med 2006; 173: 1114-
1121.
- 10. Papakonstantinou E, Roth M, Klagas I, Karakiulakis G,
Tamm M, Stolz D. COPD exacerbations are associated with
proinflammatory degradation of hyaluronic acid. Chest 2015;
148: 1497-1507.
- 11. Repine JE, Bast A, Lankhorst I. Oxidative stress in chronic
obstructive pulmonary disease. Oxidative Stress Study Group.
Am J Respir Crit Care Med 1997; 156: 341-357.
- 12. Rahman I, Adcock IM. Oxidative stress and redox regulation
of lung inflammation in COPD. Eur Respir J 2006; 28: 219-242.
- 13. Mavelli I, Rigo A, Federico R, Ciriolo MR, Rotilio G.
Superoxide dismutase, glutathione peroxidase and catalase in
developing rat brain. Biochem J 1982; 204: 535-540.
- 14. Montano M, Cisneros J, Ramirez-Venegas A, Pedraza-Chaverri
J, Mercado D, Ramos C, Sansores RH. Malondialdehyde and
superoxide dismutase correlate with FEV1
in patients with
COPD associated with wood smoke exposure and tobacco
smoking. Inhal Toxicol 2010; 22: 868-874.
- 15. Tabur S, Aksoy SN, Korkmaz H, Ozkaya M, Aksoy N, Akarsu
E. Investigation of the role of 8-OHdG and oxidative stress in
papillary thyroid carcinoma. Tumour Biol 2015; 36: 2667-2674.
- 16. Kondo S, Toyokuni S, Tanaka T, Hiai H, Onodera H, Kasai H,
Imamura M. Overexpression of the hOGG1 gene and high
8-hydroxy-2’-deoxyguanosine (8-OHdG) lyase activity in
human colorectal carcinoma: regulation mechanism of the
8-OHdG level in DNA. Clin Cancer Res 2000; 6: 1394-1400.
- 17. Valavanidis A, Vlahoyianni T, Fiotakis K. Comparative study
of the formation of oxidative damage marker 8-hydroxy2’-deoxyguanosine (8-OHdG) adduct from the nucleoside
2’-deoxyguanosine by transition metals and suspensions of
particulate matter in relation to metal content and redox
reactivity. Free Radic Res 2005; 39: 1071-1081.
- 18. Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW,
Wedzicha JA. Usefulness of the Medical Research Council
(MRC) dyspnoea scale as a measure of disability in patients
with chronic obstructive pulmonary disease. Thorax 1999; 54:
581-586.
- 19. Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline
Leidy N. Development and first validation of the COPD
Assessment Test. Eur Respir J 2009; 34: 648-654.
- 20. Carlin BW. COPD and associated comorbidities: a review of
current diagnosis and treatment. Postgrad Med 2012; 124: 225-
240.
- 21. Agusti AG. COPD, a multicomponent disease: implications for
management. Respir Med 2005; 99: 670-682.
- 22. Tzortzaki EG, Dimakou K, Neofytou E, Tsikritsaki K, Samara
K, Avgousti M, Amargianitakis V, Gousiou A, Menikou S,
Siafakas NM. Oxidative DNA damage and somatic mutations:
a link to the molecular pathogenesis of chronic inflammatory
airway diseases. Chest 2012; 141: 1243-1250.
- 23. Kirkham PA, Barnes PJ. Oxidative stress in COPD. Chest 2013;
144: 266-273.
- 24. Zuo L, He F, Sergakis GG, Koozehchian MS, Stimpfl JN,
Rong Y, Diaz PT, Best TM. Interrelated role of cigarette
smoking, oxidative stress, and immune response in COPD and
corresponding treatments. Am J Physiol Lung Cell Mol Physiol
2014; 307: L205-218.
- 25. Tsutsui H, Kinugawa S, Matsushima S. Mitochondrial oxidative
stress and dysfunction in myocardial remodelling. Cardiovasc
Res 2009; 81: 449-456.
- 26. Kasai H, Hayami H, Yamaizumi Z, SaitoH, Nishimura S.
Detection and identification of mutagens and carcinogens as
their adducts with guanosine derivatives. Nucleic Acids Res
1984; 12: 2127-2136.
- 27. James AL, Palmer LJ, Kicic E, Maxwell PS, Lagan SE, Ryan GF,
Musk AW. Decline in lung function in the Busselton Health
Study: the effects of asthma and cigarette smoking. Am J Respir
Crit Care Med 2005; 171: 109-114.
- 28. Thomson NC, Chaudhuri R, Livingston E. Asthma and
cigarette smoking. Eur Respir J 2004; 24: 822-833.
- 29. Bertram C, Hass R. Cellular responses to reactive oxygen
species-induced DNA damage and aging. Biol Chem 2008;
389: 211-220.
- 30. Aoshiba K, Zhou F, Tsuji T, Nagai A. DNA damage as a
molecular link in the pathogenesis of COPD in smokers. Eur
Respir J 2012; 39: 1368-1376.
- 31. Asami S, Hirano T, Yamaguchi R, Tomioka Y, Itoh H, Kasai H.
Increase of a type of oxidative DNA damage, 8-hydroxyguanine,
and its repair activity in human leukocytes by cigarette
smoking. Cancer Res 1996; 56: 2546-2549.
- 32. MacNee W, Tuder RM. New paradigms in the pathogenesis of
chronic obstructive pulmonary disease I. Proc Am Thorac Soc
2009; 6: 527-531.
- 33. Tkacova R, Kluchova Z, Joppa P, Petrasova D, Molcanyiova
A. Systemic inflammation and systemic oxidative stress in
patients with acute exacerbations of COPD. Respir Med 2007;
101: 1670-1676.
- 34. Seemungal T, Harper-Owen R, Bhowmik A, Moric I, Sanderson
G, Message S, Maccallum P, Meade TW, Jeffries DJ, Johnston
SL et al. Respiratory viruses, symptoms, and inflammatory
markers in acute exacerbations and stable chronic obstructive
pulmonary disease. Am J Respir Crit Care Med 2001; 164:
1618-1623.
- 35. Bafadhel M, Clark TW, Reid C, Medina MJ, Batham S,
Barer MR, Nicholson KG, Brightling CE. Procalcitonin
and C-reactive protein in hospitalized adult patients with
community-acquired pneumonia or exacerbation of asthma or
COPD. Chest 2011; 139: 1410-1418.
- 36. Sin DD, Man SFP. Biomarkers in COPD: are we there yet?
Chest 2008; 133: 1296-1298.
- 37. Qian W, Huang GZ. Neutrophil CD64 as a marker of bacterial
infection in acute exacerbations of chronic obstructive
pulmonary disease. Immunol Invest 2016; 45: 490-503.
- 38. Brusselle GG, Joos GF, Bracke KR. New insights into the
immunology of chronic obstructive pulmonary disease. Lancet
2011; 378: 1015-1026.
- 39. MacNee W. Oxidative stress and lung inflammation in airways
disease. Eur J Pharmacol 2001; 429: 195-207.
- 40. Drost EM, Skwarski KM, Sauleda J, Soler N, Roca J, Agusti A,
MacNee W. Oxidative stress and airway inflammation in severe
exacerbations of COPD. Thorax 2005; 60: 293-300.