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.	陈勇, 张宁, 饶爱霞.慢性阻塞性肺疾病血浆丙二醛和谷胱甘肽过氧化物酶的研究.中国现代医学杂志, 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.	苏丽清, 王海静, 迟海燕, 等.2型糖尿病伴阻塞性睡眠呼吸暂停患者血清蛋白质羰基水平与氧化应激状态.中国老年学杂志, 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, 杨靖, 宋沁馨, 等.8-羟基脱氧鸟苷作为DNA氧化损伤标志物在疾病诊断中的应用.药学与临床研究, 2012, 20:223-228.
7.	赵艳雪, 李理, 袁伟锋, 等.谷胱甘肽S转移酶mu5对肿瘤坏死因子α诱导人支气管上皮细胞氧化损伤的调节作用研究.中国呼吸与危重监护杂志, 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.	孔祥龙.稳定期COPD患者的IL-18、TNF-α与营养状况及预后指标的相关性研究(学位论文).中南大学, 2012.
10.	何娓娓, 顾宇彤, 王桂芳.氧化应激失衡在慢性阻塞性肺疾病患者发病及防治中的研究进展.中国呼吸与危重监护杂志, 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.	樊涛, 张宇, 蒋洪丽, 等.慢性阻塞性肺疾病患者肺组织丙二醛、白细胞介素8、肿瘤坏死因子α水平及吸烟的影响.中国呼吸与危重监护杂志, 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.	杨士芳. DNA加合物及其相关修复酶基因多态性在COPD发病中的研究(学位论文).华中科技大学, 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. 陈勇, 张宁, 饶爱霞.慢性阻塞性肺疾病血浆丙二醛和谷胱甘肽过氧化物酶的研究.中国现代医学杂志, 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. 苏丽清, 王海静, 迟海燕, 等.2型糖尿病伴阻塞性睡眠呼吸暂停患者血清蛋白质羰基水平与氧化应激状态.中国老年学杂志, 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, 杨靖, 宋沁馨, 等.8-羟基脱氧鸟苷作为DNA氧化损伤标志物在疾病诊断中的应用.药学与临床研究, 2012, 20:223-228.
7. 赵艳雪, 李理, 袁伟锋, 等.谷胱甘肽S转移酶mu5对肿瘤坏死因子α诱导人支气管上皮细胞氧化损伤的调节作用研究.中国呼吸与危重监护杂志, 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. 孔祥龙.稳定期COPD患者的IL-18、TNF-α与营养状况及预后指标的相关性研究(学位论文).中南大学, 2012.
10. 何娓娓, 顾宇彤, 王桂芳.氧化应激失衡在慢性阻塞性肺疾病患者发病及防治中的研究进展.中国呼吸与危重监护杂志, 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. 樊涛, 张宇, 蒋洪丽, 等.慢性阻塞性肺疾病患者肺组织丙二醛、白细胞介素8、肿瘤坏死因子α水平及吸烟的影响.中国呼吸与危重监护杂志, 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. 杨士芳. DNA加合物及其相关修复酶基因多态性在COPD发病中的研究(学位论文).华中科技大学, 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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