Development of secondary mitochondrial dysfunction of mononuclear blood leukocytes in patients with chronic obstructive pulmonary disease and chronic bronchitis

Abstract

Aim. To study the indicators of energy metabolism and oxidative stress in mononuclear leukocytes of peripheral blood and to assess the possibility of mitochondrial dysfunction development in chronic obstructive pulmonary disease and chronic bronchitis.

Methods. The study included 50 patients aged 40 to 75 years with chronic obstructive pulmonary disease (COPD) or chronic bronchitis. The first group included 13 patients with chronic bronchitis. In accordance with the GOLD spirometric classification, the second and third groups included patients with COPD of moderate severity (COPD 2) (n=17) and severe COPD (COPD 3) (n=20) respectively. In the isolated mononuclear leukocytes, the activity of superoxide dismutase (SOD), succinate dehydrogenase (SDH) and concentration of succinate were determined, a complex evaluation of oxidative modification of proteins was performed.

Results. Patients with chronic bronchitis compared to patients with COPD 2 and COPD 3 were found to have in mononuclear leukocytes higher activity of SOD by 3.38 times (p=0.0025) and 3.15 times (p=0.0058), higher activity of SDH by 4.55 times (p=0.0281) and 2.5 times (p=0.0263) and higher succinate concentration by 2.05 (p=0.0133) and 1.89 (p=0.005) times respectively. The level of spontaneously oxidized modified proteins in the group of patients with chronic bronchitis decreased by 2.45 (p=0.0176) and 2.94 (p=0.0168) times compared to the patients of groups 2 and 3, respectively There was a decrease in the reserve-adaptive potential of oxidative modification of proteins in COPD in the form of an increase of the ratio of spontaneously oxidized-modified proteins to metal-induced oxidized proteins by 1.58 times (p=0.0301) between groups 1 and 2, and by 1.44 times between groups 2 and 3 (p=0.0446).

Conclusion. In mononuclear leukocytes of COPD patients, secondary mitochondrial dysfunction is observed accompanied by significant oxidative damage of lymphocytes and monocytes. Patients with severe COPD compared to patients with COPD of moderate severity have less reserve-adaptive potential for the oxidative modification of mononuclear leukocyte proteins, which probably reflects a more severe course of the disease.

Keywords

COPD / mitochondrial dysfunction / oxidative modification of proteins / mononuclear leukocytes

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Bel’skikh E.S., Uryas’ev O.M., Zvyagina V.I., Faletrova S.V.