The Mechanism of Action of Ethoxidol on Oxidative Stress Indices in Heart Failure and Hypotension.

V G Kukes, O K Parfenova, B K Romanov, A B Prokofiev, E V Parfenova, N G Sidorov, A A Gazdanova, L I Pavlova, V I Zozina, A D Andreev, T V Aleksandrova, S V Chernova, G V Ramenskaya
Author Information
  1. V G Kukes: Academician of the Russian Academy of Sciences, Professor, Department of Clinical Pharmacology and Propedeutics of Internal Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia; Head of the Scientific Direction "Pharmacology", Scientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of the Russian Federation, 8, Bld. 2, Petrovsky Boulevard, Moscow, 127051, Russia.
  2. O K Parfenova: Student, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia.
  3. B K Romanov: Deputy Director General on Scientific Work, Scientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of the Russian Federation, 8, Bld. 2, Petrovsky Boulevard, Moscow, 127051, Russia.
  4. A B Prokofiev: Professor, Department of Clinical Pharmacology and Propedeutics of Internal Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia; Director of the Clinical Pharmacology Center, Scientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of the Russian Federation, 8, Bld. 2, Petrovsky Boulevard, Moscow, 127051, Russia.
  5. E V Parfenova: Professor, Corresponding Member of the Russian Academy of Sciences, Deputy Director General, National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation, 15A 3 Cherepkovskaya St., Moscow, 121552, Russia; Director of the Institute of Experimental Cardiology, National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation, 15A 3 Cherepkovskaya St., Moscow, 121552, Russia.
  6. N G Sidorov: Student, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia.
  7. A A Gazdanova: Associate Professor, Department of Clinical Pharmacology and Propedeutics of Internal Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia.
  8. L I Pavlova: Associate Professor, Department of Clinical Pharmacology and Propedeutics of Internal Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia.
  9. V I Zozina: PhD Student, Department of Clinical Pharmacology and Propedeutics of Internal Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia.
  10. A D Andreev: Student, Medical Faculty, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia.
  11. T V Aleksandrova: Senior Analyst, Scientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of the Russian Federation, 8, Bld. 2, Petrovsky Boulevard, Moscow, 127051, Russia.
  12. S V Chernova: Associate Professor, Department of Pharmaceutical and Toxicological Chemistry named after A.P. Arzamastsev, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia.
  13. G V Ramenskaya: Director, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia; Head of the Department of Pharmaceutical and Toxicological Chemistry named after A.P. Arzamastsev, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Malaya Trubetskaya St., Moscow, 119991, Russia.

Abstract

was to study the effect of 2-ethyl-6-methyl-3-hydroxypyridine malate (Ethoxidol) on the concentration of oxidative stress metabolites in patients with chronic heart failure (CHF) and hypertension.
MATERIALS AND METHODS: 126 patients with FC I-III CHF have been examined. In addition to their individual therapy these patients received intravenous infusions of Ethoxidol. Blood content of 2,3-diphosphoglycerate (2,3-DPG), oxygen tension (рО), pH, concentration of total peroxides, lactate, and aldosterone were identified. 2,3-DPG levels (g/L erythrocytes) in whole blood samples were determined by an enzyme assay using the reagent kit (Rosh, Germany), values of рО, рСО, рН, lactate in the venous blood were measured using gas analyzer Stat Profil pHOx Ultra (Nova Biomedical, USA). Indices of oxidative stress, i.e. the concentration of plasma total peroxides, were investigated by ELISA using OxyStat kit (Biomedica, Austria). Peripheral venous blood samples were collected from all patients before and 6 days after the daily intravenous Ethoxidol infusion.
RESULTS: In patients with FC I, II, III CHF, on day 7 after intravenous Ethoxidol infusion at a dose of 100 mg/day, statistically significant growth (p=0.0002) of PaO level by 15.7, 17.4, and 22.8%, respectively, was noted. In patients with FC I, II, III CHF in the group receiving standard therapy, statistically significant (p=0.002) reduction of 2,3-DPG level by 2.7, 2.4, and 4.0%, respectively, was registered. On day 7 after the infusion of Ethoxidol at a dose of 100 mg/day, its decrease by 5.7, 10.5, and 26.2%, respectively (p<0.0001), was also observed.
CONCLUSION: The increased concentrations of active oxygen forms have been established to negatively affect various bodily functions and adversely influence the pathophysiology of numerous diseases. Application of antioxidants, including Ethoxidol presented by us in this article, may become a clue to the development of preventive measures for many serious diseases.

Keywords

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Word Cloud

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