Association between various antioxidants in normals and chronic obstructive pulmonary disease, their alteration and impact of smoking and disease on levels of antioxidants

Background: There is total alteration of various antioxidants in response to the oxidative stress, which is one of the major patho-physiologic hallmarks in chronic obstructive pulmonary disease (COPD) development. This study aims to establish the correlation between different antioxidants in normals and COPD, study the alteration in the correlation due to COPD and smoking as well as the impact of COPD and smoking on antioxidants levels.Methods: Study comprises of 96 normals as group I and 96 COPD patients as group II. The antioxidants albumin (Alb), bilirubin (Bil), uric acid (UA) ceruloplasmin (Cp), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase 3 (SOD3) were estimated.Results: Significant lower serum Alb, UA, SOD3 and increased serum Cp and GSHPx were found in Group II. Significant correlation was found between Alb and UA (r=0.24); Bil and UA (r=0.26); Alb and CAT (r=0.211) and SOD3 and CAT (r=0.318) in normals. However, these correlations were altered in COPD where Alb correlates with Bil (r=0.235); UA with CAT (r=0.203) and SOD3 with GSHPx (r=-0.27). The correlation between SOD3 and CAT remained unaltered. Similar correlation of UA with Alb and Bil was observed in nonsmoker normals and between SOD3 and CAT in smoker normals. In COPD, no correlation was seen in nonsmokers, while in smokers Alb correlates with Bil (r=0.316) and SOD3 with CAT (r=0.317).Conclusions: These alterations may have clinical ramifications in further understanding the pathogenesis of COPD and developing therapeutic approaches.

Total Antioxidant Capacity: Correlation with Other Antioxidants and Clinical Utility of Their Levels in Chronic Obstructive Pulmonary Disease.

Oxidative stress is one of the major pathophysiologic hallmarks in the development of COPD and lung is protected against this by enzymatic and non-enzymatic antioxidants. Total antioxidant activity (TAC), may give more relevant biological information about the individual's overall antioxidant status compared to individual components. This study aims to evaluate correlation between TAC and other antioxidants bilirubin, albumin, urate and ceruloplasmin (CP) and explore the clinical utility of their levels in diagnosis of COPD. Study Design: Comparison study. Place and Duration of Study: Cardio Thoracic Centre, Pune and Department of Biochemistry, AFMC, Pune during Dec 2010 to Aug 2012. Methodology: Study comprised of 86 normals as controls group and 86 confirmed COPD patients as COPD group. CP was estimated by patented kinetic method of Somani and Ambade, while all other analytes were estimated by using commercially available kits. Results: CP was significantly higher in COPD patients (1392.8±281.6 IU/L) as compared to controls (1006.2±236.1 IU/L) while levels of albumin, urate and TAC were significantly lower in COPD patients. The levels in COPD and controls are albumin: 3.8±0.5 and 4.3± 0.4g/dL; urate: 4.4±1.3 and 5±1.3 mg/dL; TAC: 27.7±6.9 and 36±8.2 mmolTE/L respectively. No appreciable correlation was noticed between any individual antioxidant and TAC. Conclusion: CP and TAC showed statistically significant differences between controls and COPD patients and may have clinical utility in the management of COPD. However, the estimation of TAC is to be done with extreme care.

Oxidative Stress in Chronic Obstructive Pulmonary Disease Alters Ferroxidase Activity of Ceruloplasmin.

Aims: Oxidative stress is one of the major patho-physiologic hallmarks in the development of COPD. Ceruloplasmin, the major serum inhibitor of lipid peroxidation has been documented as a main extracellular antioxidant in serum and plays a role in preventing lung injury, and an abnormality in its oxidative inhibition could be involved in pathogenesis of COPD. This study aims to estimate levels of ceruloplasmin and its ferroxidase activity in COPD and compare with that in controls to explore their utility in COPD. Study Design: Comparison study. Place and Duration of Study: Department of Biochemistry, AFMC, Pune. Subjects for COPD were selected from the patients reporting with symptoms of COPD to respiratory OPD of Cardio Thoracic Centre, Pune, during Dec 2010 to Aug 2012. Methodology: Study comprised of two groups: Group I of 77 normal as controls (61 men, 16 women; age range 27-90 years) and Group II of 92 COPD patients (70 men, 22 women; age range 45 - 97 years). Both the groups were further divided into smoker and nonsmoker groups. Ferroxidase activity of ceruloplasmin was estimated by indigenous patented kinetic method of Somani and Ambade while ceruloplasmin was estimated by immunotubidimetric method using commercially available kit. Results: Serum ceruloplasmin and ferroxidase activity were significantly higher in COPD patients as compared to normal controls. Mean ± SD in COPD versus controls respectively are ceruloplasmin: 45.84 ± 12.7 mg/dL versus 37 ± 9.7 mg/dL; ferroxidase: 1324.9 ± 278.53 IU/L versus 980.5 ± 202.3 IU/L, P< .001. Statistically significant & good correlation (r > 0.7) was found between ceruloplasmin and ferroxidase in controls, nonsmoker controls and smoker controls (r = 0.76, 0.71 and 0.79 respectively) while in COPD, COPD nonsmokers and COPD smokers, no correlation was found (r = 0.00, 0.29 and 0.09 respectively). Conclusion: There is alteration in the ferroxidase activity of ceruloplasmin in COPD. Future studies with quantification of carbonyl residues or other groups in ceruloplasmin molecule leading to altered oxidative or ferroxidase activity of ceruloplasmin may provide further evidence to support a role of oxidative stress in COPD.