Succinate and succinate dehydrogenase of mononuclear blood leukocytes as markers of adaptation of mitochondria to hypoxia in patients with exacerbation of chronic obstructive pulmonary disease

Abstract

Aim. To study the concentration of succinate and the activity of succinate dehydrogenase (SDH) of mononuclear blood leukocytes as markers of rapid adaptation of mitochondria to hypoxia in patients with exacerbation of chronic obstructive pulmonary disease (COPD).

Materials and Methods. The study involved 58 patients with COPD and 13 conventionally healthy volunteers of 40-75 years of age. In accordance with GOLD 2018 principles of complex assessment, the patients were divided to groups B (n=18), C (n=20), D (n=20) comparable in age, FEV₁ and in pack-of-cigarettes/year index. Patients of D group were characterized by more pronounced hypoxemia. Activity of SDH and concentration of succinate were determined in mononuclear leukocytes isolated from blood.

Results. Patients with exacerbation of COPD divided to groups on the basis of the frequency of exacerbations and evidence of symptoms, were characterized by different severity of disorders of mitochondrial functions of mononuclear leukocytes. Patients of C group had the highest succinate concentration (428 [357;545] nmol/10⁶ cells in I ml of suspension) and SDH activity (64[56;73] nmol of succinate/min * 10⁶ cells of 1 ml of suspension) in mononuclear leukocytes as compared to groups B (1.43-times reduction of succinate, p<0.002; 1.88-times reduction of SDH, p=0.0015) and D (2.06-times reduction of succinate, p<0.0001; 4.26-times reduction of SDH, p<0.0001). Patients of D group demonstrated the most pronounced reduction of markers of adaptation to hypoxia.

Conclusions. A small amount of symptoms in exacerbation of COPD is associated with the highest parameters of the mechanism of rapid adaptation of mitochondria of mononuclear leukocytes to hypoxia. Existence of evident symptoms and frequent exacerbations in patents is associated with a severe frustration of mechanisms of adaptation of mitochondria to hypoxia.

Keywords

COPD / mitochondrial dysfunction / succinate / mononuclear leukocytes

References

[1] Barabanova EN. GOLD 2017: what change were made in global strategy of treatment of chronic obstructive pulmo-nary disease and why? Pulʹmono-logiâ. 2017;27(2):274-82. (In Russ). doi:10.18093/ 0869-0189-2017-27-2-274-282

[2] Барабанова Е.Н. GOLD 2017: что и почему изменилось в глобальной стратегии лечения хронической об-структивной болезни легких? // Пульмонология. 2017. Т. 27, №2. С. 274-282. doi:10.18093/0869-0189-2017-27-2-274-282

[3] Nizov AA, Ermachkova AN, Abrosimov VN, et al. Complex assessment of the degree of chronic obstructive pulmo-nary disease COPD severity on out-patient visit. I.P. Pavlov Russian Medical Biological Herald. 2019;27(1):59-65. (In Russ). doi:10.23888/ PAVLOVJ201927159-65

[4] Низов А.А., Ермачкова А.Н., Абросимов В.Н., и др. Комплексная оценка степени тяжести ХОБЛ на амбула-торно-поликлиническом приеме // Российский медико-биологический вестник имени академика И.П. Павлова. 2019. Т. 27, №1. С. 59-65. doi:10.23888/PAVLOVJ201927159-65

[5] Nam HS, Izumchenko E, Dasgupta S, et al. Mitochondria in chronic obstructive pulmonary disease and lung cancer: where are we now? Biomarkers in Medicine. 2017;11(6):475-89. doi:10.2217/bmm-2016-0373

[6] Nam H.S., Izumchenko E., Dasgupta S., et al. Mitochondria in chronic obstructive pulmonary disease and lung can-cer: where are we now? // Biomarkers in Medicine. 2017. Vol. 11, №6. P. 475-489. doi:10.2217/bmm-2016-0373

[7] Agrawal A, Mabalirajan U. Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochon-dria. American Journal of Physiology. Lung Cellular and Molecular Physiology. 2016; 310(2):103-13. doi:10.1152/ajplung.00320.2015

[8] Agrawal A., Mabalirajan U. Rejuvenating cellular respiration for optimizing respiratory function: targeting mito-chondria // American Journal of Physiology. Lung Cellular and Molecular Physiology. 2016. Vol. 310, №2. P. 103-113. doi:10.1152/aj-plung.00320.2015

[9] Lerner CA, Sundar IK, Rahman I. Mitochondrial redox system, dynamics, and dysfunction in lung inflammaging and COPD. International Journal of Biochemistry & Cell Biology. 2016;81(Pt B):294-306. doi:10.1016/j.biocel.2016.07.026

[10] Lerner C.A., Sundar I.K., Rahman I. Mitochondrial redox system, dynamics, and dysfunction in lung inflammaging and COPD // The International Journal of Biochemistry & Cell Biology. 2016. Vol. 81, Pt. B. P. 294-306. doi:10.1016/j.biocel.2016.07.026

[11] Li LA, Lebed'ko OA, Kozlov VK. Assessment of mitochondrial dysfunction in children with community-acquired pneumonia. Far East Medical Journal. 2015;(2):30-6. (In Russ).

[12] Ли Л.А., Лебедько О.А., Козлов В.К. Оценка дисфункции митохондрий при внебольничной пневмонии у детей // Дальневосточный медицинский журнал. 2015. №2. С. 30-36.

[13] Singh S, Verma SK, Kumar S, et al. Evaluation of Oxidative Stress and Antioxidant Status in Chronic Obstructive Pulmonary Disease. Scandinavian Jour-nal of Immunology. 2017;85(2):130-7. doi:10.1111/ sji.12498

[14] Singh S., Verma S.K., Kumar S., et al. Evaluation of Oxidative Stress and Antioxidant Status in Chronic Obstructive Pulmonary Disease // Scandinavian Journal of Immunology. 2017. Vol. 85, №2. P. 130-137. doi:10.1111/sji.12498

[15] Lobanova EG, Kondratiyeva EV, Mineyeva EE, et al. The membrane potential of mitochondria of thrombocytes in patients with chronic obstructive disease of lungs. Russian Clinical Laboratory Diagnostics. 2014;59(6):13-6. (In Russ).

[16] Лобанова Е.Г., Кондратьева Е.В., Минеева Е.Е., и др. Мембранный потенциал митохондрий тромбоцитов у пациентов с хронической обструктивной болезнью легких // Клиническая лабораторная диагностика. 2014. Т. 59, №6. С. 13-16.

[17] Denisenko YuK, Novgorodtseva TP, Vitkina TI, et al. Mitochondrial dysfunction in chronic obstructive pulmonary disease. Byulleten’ Fiziologii i Patologii Dykhaniya. 2016;(60):28-33. (In Russ). doi:10.12737/20048

[18] Денисенко Ю.К., Новгородцева Т.П., Виткина Т.И., и др. К вопросу о митохондриальной дисфункции при хронической обструктивной болезни легких // Бюллетень физиологии и патологии дыхания. 2016. №60. С. 28-33. doi:10.12737/20048

[19] Lukyanova LD, Kirova YI. Mitochondria-control-led signaling mechanisms of brain protection in hypoxia. Frontiers in Neuroscience. 2015;9:320. doi: 10.3389/fnins.2015.00320

[20] Lukyanova L.D., Kirova Y.I. Mitochondria-controlled signaling mechanisms of brain protection in hypoxia // Fron-tiers in Neuroscience. 2015. Vol. 9. P. 320. doi:10.3389/fnins.2015.00320

[21] Belskikh ES, Uryas'ev OM, Zvyagina VI, et al. Investigation of oxidative stress and function of mitochondria in mononuclear leukocytes of blood in patients with chronic bronchitis and with chronic obstructive pulmonary disease. Nauka Molodyh (Eruditio Juvenium). 2018;6(2):203-10. (In Russ). doi:10.23888/HMJ201862203-210

[22] Бельских Э.С., Урясьев О.М., Звягина В.И., и др. Исследование окислительного стресса и функции митохон-дрий в мононуклеарных лейкоцитах крови у больных с хроническим бронхитом и с хронической обструк-тивной болезнью легких // Наука молодых (Eruditio Juvenium). 2018. Т. 6, №2. С. 203-210. doi:10.23888/HMJ201862203-210

[23] Metody biokhimicheskikh issledovaniy: (Lipidnyy i ehnergeticheskiy obmen). Leningrad: Izdatel’stvo Leningrad-skogo gosudarstvennogo universiteta; 1982. (In Russ).

[24] Методы биохимических исследований: (Липидный и энергетический обмен). Л.: Издательство ЛГУ; 1982.

RIGHTS & PERMISSIONS

Belskikh E.S., Uryasiev O.M., Zvyagina V.I., Faletrova S.V.