Expression and Clinical Significance of Oxidative Stress Markers in Serum of Patients with Stable Chronic Obstructive Pulmonary Disease_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

JiangXuelian , ZhongPing , HuangChengliang , MengYuanzhu , HeFang ,  FanXianming

Second Department of Respiratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China;

Corresponding?author：

FanXianming, Email: fxm129@163.com

Keywords：

Chronic obstructive pulmonary disease; Oxidative stress; Malondialdehyde; Protein carbonyls; 8-hydroxy-2'-deoxyguanosine; Total antioxidant capacity

DOI：

10.7507/1671-6205.2016125

Video：

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Objective To detect the level of oxidative stress markers in serum, including malondialdehyde (MDA), protein carbonyls (PC), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and total antioxidant capacity (TAC), in patients with stable chronic obstructive pulmonary disease (COPD), and explore the impacts of oxidant/antioxidant imbalance in pathogenesis of COPD. Methods Two hundred stable COPD patients (the COPD group) and 100 healthy individuals (the control group) were recruited in the study. The concentrations of MDA, PC, 8-OHdG and TAC in serum were detected. Pulmonary function test was performed and the general informations for each subjects were collected. The COPD patients were divided into a smoking subgroup and a non-smoking subgroup, or divided into a mild-moderate airflow limitation subgroup and a severe-extremely severe airflow limitation subgroup. Results The levels of serum MDA, PC and 8-OHdG in the COPD group were significantly higher than those in the control group (all P < 0.01), but the level of serum TAC was significantly lower than that in the control group (P < 0.01). In the COPD patients, the levels of PC and 8-OHdG in the smoking subgroup were significantly higher than those in the non-smoking subgroup (both P < 0.05). The level of PC in the severe-extremely severe airflow limitation subgroup was significantly higher when compared with the mild-moderate airflow limitation subgroup (P < 0.01). Multiple linear regression analysis showed that the levels of PC and 8-OHdG were negatively related with FEV₁% pred in the COPD patients, and the PC had greater impacts than 8-OHdG (β=-0.230, -0.219, P < 0.01). Conclusion Smoking can induce the abnormal increase of PC and 8-OHdG in serum which are negatively related with FEV₁% pred in COPD patients, which suggests that oxidative stress might play an important role in pathogenesis of COPD.

Citation： JiangXuelian, ZhongPing, HuangChengliang, MengYuanzhu, HeFang, FanXianming. Expression and Clinical Significance of Oxidative Stress Markers in Serum of Patients with Stable Chronic Obstructive Pulmonary Disease. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(6): 542-547. doi: 10.7507/1671-6205.2016125 Copy

1.	Ghorbani A, Feizpour A, Hashemzahi M, et al. The effect of adipose derived stromal cells on oxidative stress level, lung emphysema and white blood cells of guinea pigs model of chronic obstructive pulmonary disease.Daru, 2014, 22:26.
2.	陳勇, 張寧, 饒愛霞.慢性阻塞性肺疾病血漿丙二醛和谷胱甘肽過氧化物酶的研究.中國現代醫學雜志, 2005, 15:3453-3454, 3457.
3.	Barreiro E, Gea J, Matar G, et al. Expression and carbonylation of creatine kinase in the quadriceps femoris muscles of patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol, 2005, 33:636-642.
4.	蘇麗清, 王海靜, 遲海燕, 等.2型糖尿病伴阻塞性睡眠呼吸暫停患者血清蛋白質羰基水平與氧化應激狀態.中國老年學雜志, 2014, 34:592-593.
5.	Ben Anes A, Fetoui H, Bchir S, et al. Increased oxidative stress and altered levels of nitric oxide and peroxynitrite in Tunisian patients with chronic obstructive pulmonary disease:correlation with disease severity and airflow obstruction. Biol Trace Elem Res, 2014, 161:20-31.
6.	高玉楠, 楊靖, 宋沁馨, 等.8-羥基脫氧鳥苷作為DNA氧化損傷標志物在疾病診斷中的應用.藥學與臨床研究, 2012, 20:223-228.
7.	趙艷雪, 李理, 袁偉鋒, 等.谷胱甘肽S轉移酶mu5對腫瘤壞死因子α誘導人支氣管上皮細胞氧化損傷的調節作用研究.中國呼吸與危重監護雜志, 2016, 15:284-288.
8.	Arja C, Surapaneni KM, Raya P, et al. Oxidative stress and antioxidant enzyme activity in South Indian male smokers with chronic obstructive pulmonary disease. Respirology, 2013, 18:1069-1075.
9.	孔祥龍.穩定期COPD患者的IL-18、TNF-α與營養狀況及預后指標的相關性研究(學位論文).中南大學, 2012.
10.	何娓娓, 顧宇彤, 王桂芳.氧化應激失衡在慢性阻塞性肺疾病患者發病及防治中的研究進展.中國呼吸與危重監護雜志, 2011, 10:200-201.
11.	Ismail M, Hossain MF, Tanu AR, et al. Effect of spirulina intervention on oxidative stress, antioxidant status, and lipid profile in chronic obstructive pulmonary disease patients. Biomed Res Int, 2015, 2015:486120.
12.	樊濤, 張宇, 蔣洪麗, 等.慢性阻塞性肺疾病患者肺組織丙二醛、白細胞介素8、腫瘤壞死因子α水平及吸煙的影響.中國呼吸與危重監護雜志, 2012, 11:218-222.
13.	Antus B, Harnasi G, Drozdovszky O, et al. Monitoring oxidative stress during chronic obstructive pulmonary disease exacerbations using malondialdehyde. Respirology, 2014, 19:74-79.
14.	Bartoli ML, Novelli F, Costa F, et al. Malondialdehyde in exhaled breath condensate as a marker of oxidative stress in different pulmonary diseases. Mediators Inflamm, 2011, 2011:891752.
15.	Zeng M, Li Y, Jiang Y, et al. Local and systemic oxidative stress status in chronic obstructive pulmonary disease patients. Can Respir J, 2013, 20:35-41.
16.	Ahmad A, Shameem M, Husain Q. Altered oxidant-antioxidant levels in the disease prognosis of chronic obstructive pulmonary disease. Int J Tuberc Lung Dis, 2013, 17:1104-1109.
17.	Rodriguez DA, Kalko S, Puig-Vilanova E, et al. Muscle and blood redox status after exercise training in severe COPD patients. Free Radic Biol Med, 2012, 52:88-94.
18.	Kirkham PA, Caramori G, Casolari P, et al. Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2011, 184:796-802.
19.	Kirkham PA, Barnes PJ. Oxidative stress in COPD. Chest, 2013, 144:266-273.
20.	Igishi T, Hitsuda Y, Kato K, et al. Elevated urinary 8-hydroxydeoxyguanosine, a biomarker of oxidative stress, and lack of association with antioxidant vitamins in chronic obstructive pulmonary disease. Respirology, 2003, 8:455-460.
21.	楊士芳. DNA加合物及其相關修復酶基因多態性在COPD發病中的研究(學位論文).華中科技大學, 2009.
22.	Tzortzaki EG, Dimakou K, Neofytou E, et al. Oxidative DNA damage and somatic mutations:a link to the molecular pathogenesis of chronic inflammatory airway diseases. Chest, 2012, 141:1243-1250.
23.	Gencer M, Aksoy N, Dagli EC, et al. Prolidase activity dysregulation and its correlation with oxidative-antioxidative status in chronic obstructive pulmonary disease. J Clin Lab Anal, 2011, 25:8-13.
24.	Cosio BG, Iglesias A, Rios A, et al. Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of COPD. Thorax, 2009, 64:424-429.
25.	Ekin S, Arisoy A, Gunbatar H, et al. The relationships among the levels of oxidative and antioxidative parameters, FEV₁ and prolidase activity in COPD.Redox Rep, 2016, 15:1-4.
26.	Zheng JP, Wen FQ, Bai CX, et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON):a randomised, double-blind placebo-controlled trial. Lancet Respir Med, 2014, 2:187-194.
27.	De Backer J, Vos W, Van Holsbeke C, et al. Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients. Int J Chron Obstruct Pulmon Dis, 2013, 8:569-579.
28.	Ceylan E, Kocyigit A, Gencer M, et al. Increased DNA damage in patients with chronic obstructive pulmonary disease who had once smoked or been exposed to biomass. Respir Med, 2006, 100:1270-1276.
29.	Barreiro E, Peinado VI, Galdiz JB, et al. Cigarette smoke-induced oxidative stress:a role in chronic obstructive pulmonary disease skeletal muscle dysfunction. Am J Respir Crit Care Med, 2010, 182:477-488.
30.	Portao de Carlos S, Dias AS, Forgiarini Junior LA, et al. Oxidative damage induced by cigarette smoke exposure in mice:impact on lung tissue and diaphragm muscle. J Bras Pneumol, 2014, 40:411-420.
31.	Yang S, Wu H, Zhao J, et al. Feasibility of 8-OHdG formation and hOGG1 induction in PBMCs for assessing oxidative DNA damage in the lung of COPD patients. Respirology, 2014, 19:1183-1190.
32.	Wang CK, Lee HL, Chang H, et al. Enhancement between environmental tobacco smoke and arsenic on emphysema-like lesions in mice. J Hazard Mater, 2012, 221-222:256-263.
33.	Yigla M, Berkovich Y, Nagler RM. Oxidative stress indices in COPD--broncho-alveolar lavage and salivary analysis.Arch Oral Biol, 2007, 52:36-43.
34.	Biljak VR, Rumora L, Cepelak I, et al. Glutathione cycle in stable chronic obstructive pulmonary disease.Cell Biochem Funct, 2010, 28:448-453.
35.	Torres-Ramos YD, Garcia-Guillen ML, Olivares-Corichi IM, et al. Correlation of plasma protein carbonyls and c-reactive protein with gold stage progression in COPD patients. Open Respir Med J, 2009, 3:61-66.
36.	Barreiro E, de la Puente B, Minguella J, et al. Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2005, 171:1116-1124.
37.	Tavilani H, Nadi E, Karimi J, et al. Oxidative stress in COPD patients, smokers, and non-smokers. Respir Care, 2012, 57:2090-2094.

1. Ghorbani A, Feizpour A, Hashemzahi M, et al. The effect of adipose derived stromal cells on oxidative stress level, lung emphysema and white blood cells of guinea pigs model of chronic obstructive pulmonary disease.Daru, 2014, 22:26.
2. 陳勇, 張寧, 饒愛霞.慢性阻塞性肺疾病血漿丙二醛和谷胱甘肽過氧化物酶的研究.中國現代醫學雜志, 2005, 15:3453-3454, 3457.
3. Barreiro E, Gea J, Matar G, et al. Expression and carbonylation of creatine kinase in the quadriceps femoris muscles of patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol, 2005, 33:636-642.
4. 蘇麗清, 王海靜, 遲海燕, 等.2型糖尿病伴阻塞性睡眠呼吸暫停患者血清蛋白質羰基水平與氧化應激狀態.中國老年學雜志, 2014, 34:592-593.
5. Ben Anes A, Fetoui H, Bchir S, et al. Increased oxidative stress and altered levels of nitric oxide and peroxynitrite in Tunisian patients with chronic obstructive pulmonary disease:correlation with disease severity and airflow obstruction. Biol Trace Elem Res, 2014, 161:20-31.
6. 高玉楠, 楊靖, 宋沁馨, 等.8-羥基脫氧鳥苷作為DNA氧化損傷標志物在疾病診斷中的應用.藥學與臨床研究, 2012, 20:223-228.
7. 趙艷雪, 李理, 袁偉鋒, 等.谷胱甘肽S轉移酶mu5對腫瘤壞死因子α誘導人支氣管上皮細胞氧化損傷的調節作用研究.中國呼吸與危重監護雜志, 2016, 15:284-288.
8. Arja C, Surapaneni KM, Raya P, et al. Oxidative stress and antioxidant enzyme activity in South Indian male smokers with chronic obstructive pulmonary disease. Respirology, 2013, 18:1069-1075.
9. 孔祥龍.穩定期COPD患者的IL-18、TNF-α與營養狀況及預后指標的相關性研究(學位論文).中南大學, 2012.
10. 何娓娓, 顧宇彤, 王桂芳.氧化應激失衡在慢性阻塞性肺疾病患者發病及防治中的研究進展.中國呼吸與危重監護雜志, 2011, 10:200-201.
11. Ismail M, Hossain MF, Tanu AR, et al. Effect of spirulina intervention on oxidative stress, antioxidant status, and lipid profile in chronic obstructive pulmonary disease patients. Biomed Res Int, 2015, 2015:486120.
12. 樊濤, 張宇, 蔣洪麗, 等.慢性阻塞性肺疾病患者肺組織丙二醛、白細胞介素8、腫瘤壞死因子α水平及吸煙的影響.中國呼吸與危重監護雜志, 2012, 11:218-222.
13. Antus B, Harnasi G, Drozdovszky O, et al. Monitoring oxidative stress during chronic obstructive pulmonary disease exacerbations using malondialdehyde. Respirology, 2014, 19:74-79.
14. Bartoli ML, Novelli F, Costa F, et al. Malondialdehyde in exhaled breath condensate as a marker of oxidative stress in different pulmonary diseases. Mediators Inflamm, 2011, 2011:891752.
15. Zeng M, Li Y, Jiang Y, et al. Local and systemic oxidative stress status in chronic obstructive pulmonary disease patients. Can Respir J, 2013, 20:35-41.
16. Ahmad A, Shameem M, Husain Q. Altered oxidant-antioxidant levels in the disease prognosis of chronic obstructive pulmonary disease. Int J Tuberc Lung Dis, 2013, 17:1104-1109.
17. Rodriguez DA, Kalko S, Puig-Vilanova E, et al. Muscle and blood redox status after exercise training in severe COPD patients. Free Radic Biol Med, 2012, 52:88-94.
18. Kirkham PA, Caramori G, Casolari P, et al. Oxidative stress-induced antibodies to carbonyl-modified protein correlate with severity of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2011, 184:796-802.
19. Kirkham PA, Barnes PJ. Oxidative stress in COPD. Chest, 2013, 144:266-273.
20. Igishi T, Hitsuda Y, Kato K, et al. Elevated urinary 8-hydroxydeoxyguanosine, a biomarker of oxidative stress, and lack of association with antioxidant vitamins in chronic obstructive pulmonary disease. Respirology, 2003, 8:455-460.
21. 楊士芳. DNA加合物及其相關修復酶基因多態性在COPD發病中的研究(學位論文).華中科技大學, 2009.
22. Tzortzaki EG, Dimakou K, Neofytou E, et al. Oxidative DNA damage and somatic mutations:a link to the molecular pathogenesis of chronic inflammatory airway diseases. Chest, 2012, 141:1243-1250.
23. Gencer M, Aksoy N, Dagli EC, et al. Prolidase activity dysregulation and its correlation with oxidative-antioxidative status in chronic obstructive pulmonary disease. J Clin Lab Anal, 2011, 25:8-13.
24. Cosio BG, Iglesias A, Rios A, et al. Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of COPD. Thorax, 2009, 64:424-429.
25. Ekin S, Arisoy A, Gunbatar H, et al. The relationships among the levels of oxidative and antioxidative parameters, FEV₁ and prolidase activity in COPD.Redox Rep, 2016, 15:1-4.
26. Zheng JP, Wen FQ, Bai CX, et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON):a randomised, double-blind placebo-controlled trial. Lancet Respir Med, 2014, 2:187-194.
27. De Backer J, Vos W, Van Holsbeke C, et al. Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients. Int J Chron Obstruct Pulmon Dis, 2013, 8:569-579.
28. Ceylan E, Kocyigit A, Gencer M, et al. Increased DNA damage in patients with chronic obstructive pulmonary disease who had once smoked or been exposed to biomass. Respir Med, 2006, 100:1270-1276.
29. Barreiro E, Peinado VI, Galdiz JB, et al. Cigarette smoke-induced oxidative stress:a role in chronic obstructive pulmonary disease skeletal muscle dysfunction. Am J Respir Crit Care Med, 2010, 182:477-488.
30. Portao de Carlos S, Dias AS, Forgiarini Junior LA, et al. Oxidative damage induced by cigarette smoke exposure in mice:impact on lung tissue and diaphragm muscle. J Bras Pneumol, 2014, 40:411-420.
31. Yang S, Wu H, Zhao J, et al. Feasibility of 8-OHdG formation and hOGG1 induction in PBMCs for assessing oxidative DNA damage in the lung of COPD patients. Respirology, 2014, 19:1183-1190.
32. Wang CK, Lee HL, Chang H, et al. Enhancement between environmental tobacco smoke and arsenic on emphysema-like lesions in mice. J Hazard Mater, 2012, 221-222:256-263.
33. Yigla M, Berkovich Y, Nagler RM. Oxidative stress indices in COPD--broncho-alveolar lavage and salivary analysis.Arch Oral Biol, 2007, 52:36-43.
34. Biljak VR, Rumora L, Cepelak I, et al. Glutathione cycle in stable chronic obstructive pulmonary disease.Cell Biochem Funct, 2010, 28:448-453.
35. Torres-Ramos YD, Garcia-Guillen ML, Olivares-Corichi IM, et al. Correlation of plasma protein carbonyls and c-reactive protein with gold stage progression in COPD patients. Open Respir Med J, 2009, 3:61-66.
36. Barreiro E, de la Puente B, Minguella J, et al. Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2005, 171:1116-1124.
37. Tavilani H, Nadi E, Karimi J, et al. Oxidative stress in COPD patients, smokers, and non-smokers. Respir Care, 2012, 57:2090-2094.

Chinese Journal of Respiratory and Critical Care Medicine

Expression and Clinical Significance of Oxidative Stress Markers in Serum of Patients with Stable Chronic Obstructive Pulmonary Disease

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